CN116457008A

CN116457008A - Modified coronavirus structural proteins

Info

Publication number: CN116457008A
Application number: CN202180072506.1A
Authority: CN
Inventors: P-O·拉沃伊; M-A·迪奥斯特
Original assignee: Medicago Inc
Current assignee: Aramis Biotechnology Co
Priority date: 2020-09-01
Filing date: 2021-08-31
Publication date: 2023-07-18

Abstract

Modified coronavirus spike (S) proteins, virus-like particles (VLPs) comprising the modified S proteins, and nucleic acids encoding the modified S proteins are provided. Methods for the production of the modified S proteins and VLPs in a host or host cell are also described. The modified S protein may comprise a transmembrane domain (TM) or a portion of TM and a Cytoplasmic Tail (CT) or a portion of CT, wherein the CT or portion of CT is derived from influenza Hemagglutinin (HA) protein, and wherein the TM or portion of TM is heterologous to the CT or portion of CT. Furthermore, methods of inducing immunity to a coronavirus infection in a subject are described, comprising administering to the subject a composition comprising a modified coronavirus (S) protein or VLP.

Description

Modified coronavirus structural proteins

Technical Field

The present disclosure relates to modified viral structural proteins. The invention also relates to virus-like particles (VLPs) comprising modified viral structural proteins and methods of producing VLPs in a host or host cell.

Background

Coronaviruses (CoV) are the largest group of viruses belonging to the order nimoravirales (Nidovirales), which includes the coronaviridae (Coronavirinae), arterividae (Arteriviridae), nyaviridae (mesoviridae) and baculoviridae (Roniviridae). The coronaviridae subfamily includes one of the two subfamilies of the coronaviridae family, and the other is the Torovirinae subfamilies (Torovirinae). The subfamily coronaviridae is further subdivided into four genera, namely, alpha-coronavirus, beta-coronavirus, gamma-coronavirus and delta-coronavirus. Members of the alpha-and beta-coronaviruses are found only in mammals. The genus alpha-coronavirus includes two human viruses, HCoV-229E and HCoV-NL63. Important animal alpha-coronaviruses are porcine transmissible gastroenteritis virus and feline transmissible peritonitis virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, also known as 2019-nCoV and HCoV-19) is a new spectrum of Beta-coronavirus type B (Beta-CoV) and causes coronavirus disease (COVID-19) in 2019, a respiratory disease with high mortality and morbidity, which has a significant impact on public health worldwide. Because of the latency and transmissibility of the virus, an outbreak of SARS-CoV-2 (such as the pandemic beginning in 2020) is a significant challenge for healthcare systems. Thus, there is an urgent need for treatment for covd-19, but long-term management of SARS-CoV-2 outbreaks would require an effective vaccine.

As shown by recent cryoelectron tomography and cryoelectron microscopy studies, the viral particles of coronaviruses are spherical with a diameter of about 118-140nm.

The most prominent structural feature of coronaviruses is the barlike spike projections emanating from the surface of the viral particle. Coronavirus particles consist of a helical nucleocapsid structure, formed by the association between nucleocapsid (N) phosphoproteins and viral genomic RNAs, surrounded by a lipid bilayer in which three or four types of structural proteins are inserted: spike protein (S), membrane protein (M) and envelope protein (E), and hemagglutinin-esterase (HE) proteins (Masters PS.the molecular biology of corenaviruses.adv viruses Res.2006; 66:193-292) for only certain coronaviruses.

Membrane protein (M) is the most abundant structural protein in viral particles. It is a small (-25-30 kDa) protein with three transmembrane domains and is thought to confer virion shape. The envelope protein (E) is a short, intact membrane protein consisting of 76-109 amino acids, ranging in size from 8.4kDa to 12 kDa. Primary and secondary structures show that E has a short hydrophilic amino terminus consisting of 7-12 amino acids followed by a large hydrophobic transmembrane domain (TMD) consisting of 25 amino acids, and a terminus with a long hydrophilic carboxyl terminus, which comprises a majority of proteins. The E protein is involved in some aspects of the viral life cycle such as assembly, budding, envelope formation and pathogenesis.

Spike (S) protein is a glycoprotein which recognizes the host receptors of various coronaviruses and is necessary for fusion of the virus and host cell membrane for entry of the virus into the cell (Belouzard et al, viruses 2012Jun;4 (6): 1011-33). As the major glycoprotein on the surface of the viral envelope, the S protein of the coronaviridae is the primary target of neutralizing antibodies raised by natural infection (including SARS-CoV-2 infection) and is a key antigen for targeting experimental vaccine candidates.

The SARS-CoV-2S protein (as well as the S protein of other coronaviruses) was initially synthesized as a precursor protein. The individual precursor S proteins form homotrimers and undergo glycosylation and signal peptide removal processing within the Golgi apparatus compartment. The S protein requires two-step protease mediated activation to aid in membrane fusion. SARS-CoV-2S protein is characterized by an RRAR Furin (Furin) cleavage site at the S1/S2 junction, which is presumed to be processed in the golgi compartment to produce two different polypeptides: s1 and S2 polypeptides (or subunits) that remain non-covalently bound as S1/S2 protomers within homotrimers in the pre-fusion conformation (Walls et al, cell 2020 181 (2) pages 281-292; li et al eLife 2019; 8:e51230). Cleavage by furin at the S1/S2 junction and cleavage at the S2' site upstream of the fusion peptide occurs during entry of the virus into the cell surface or endosome and may be mediated by some proteases.

The trimer remains in a pre-fusion conformation prior to binding to a target receptor on a host cell via a Receptor Binding Domain (RBD) epitope. Receptor binding destabilizes the pre-fusion trimer, resulting in shedding of the S1 subunit, and the S2 subunit is converted to a stable post-fusion protein conformation by fusion of the virus to the cell membrane (Wrapp et al Science 13mar 2020, volume 367, 6483, pages 1260-1263). Antibodies neutralizing individuals infected with SARS-CoV-2 have been shown to target RBD of the S1 subunit of the S protein (Premkumar, L.,2020Science Immunology 2020, 6, 11, 5, 48).

Stabilization of the S protein extracellular domain in the pre-fusion conformation tends to increase recombinant expression yields, possibly by preventing induction or misfolding due to the trend towards more stable post-fusion structures (Hsieh et al Science 2020,369 1501-1505).

Mutations in the extracellular domain of the S protein have been shown to assist in stabilization of the pre-fusion conformation. WO 2018/081318 and the matched publication by Pallesen, J et al (PNAS, 2017, 8, 29, 114 (35)) disclose a biproline substitution at or near the junction between heptad repeat region 1 (HR 1) and the central helix, which allows stabilization of the S ectodomain trimer of MERS-CoV spike protein in the pre-fusion conformation and substitution to prevent cleavage of the protease at the S1/S2 cleavage site and cleavage at the S2' cleavage site of the S ectodomain. Replacement of stable SARS-CoV-2S protein with biproline at homologous amino acid residues has been used to determine high resolution structure by cryoEM (Wrapp et al Science 2020 367,1260-1263; walls et al Cell 2020,181,281-292). Furthermore, disruption of the furin recognition site is thought to allow the S protein to remain in the pre-fusion conformation (Wrapp et al Science 2020 367, 1260-1263). However, even with these substitutions, the extracellular domain of the SARS-CoV-2S protein remains unstable and difficult to reliably produce in mammalian cells, thereby hampering the development of effective and high-yield subunit vaccines (Hsieh et al Science 2020,369 1501-1505).

Hsieh et al (Science 2020,369 p.1501-1505) designed and expressed more than 100 structurally directed variants of SARS-CoV-2 spike protein in mammalian cells based on previously defined frozen EM structures. These variants are characterized biochemically, biophysically, and structurally to identify substitutions that result in increased yields and stability. Hsieh et al report various proline, disulfide, salt bridge and cavity filling substitutions that increase the expression and/or stability of spike proteins relative to biproline substitutions. The best identified variant HexaPro has 6 beneficial proline substitutions resulting in 10-fold higher expression than its parent construct and is able to withstand heat stress, room temperature storage and multiple freeze-thawing.

The S2 subunit can be divided into three domains: large extracellular domain, transmembrane domain (TM) and Cytoplasmic Tail (CT). The cytoplasmic tail of the S protein has previously been shown to be required for assembly. Two different retention information can be found in CT of the coronaviridae: i) Endoplasmic Reticulum Recovery Signal (ERRS) and/or ii) tyrosine-dependent localization information (YxxI or YxxF motifs). ERRS includes a binary KxHxx motif that binds to the exosome complex I (COPI). When co-expressed with SARS membrane (M) protein, this motif is necessary for the localization of SARS S protein to the ERGIC/Golgi region, and localization can be disrupted by mutation of the KxHxx motif (McBride et al J.Virol.Feb 2007,81 (5) 2418-2428). The S protein containing ERRS is recruited into COPI vesicles and retrograde from the Golgi apparatus back into the Endoplasmic Reticulum (ER). Repeated cycling of the S protein between the ER and golgi leads to intracellular retention of the S protein. The S proteins of both alpha-and beta-coronaviruses include ERRS (Ujike et al Journal of General Virology (2016), 97, 1853-1864).

The S proteins of the beta-coronaviruses, such as MERS-CoV, SARS-CoV and SARS-CoV2, have ERRS only and cannot be retained intracellularly, resulting in release of the S protein into the plasma membrane. Mutant SARS-CoV S proteins lacking ERRS are transported to the plasma membrane, whereas native S proteins, when co-expressed with M protein, interact with M protein in the vicinity of the budding site, resulting in intracellular retention of S protein, suggesting that ERRS of SARS-CoV promotes specific accumulation of S protein in the posterolateral Golgi compartment by interacting with M protein, resulting in the introduction of S protein into VLP (Ujike et al Journal of General Virology (2016), 97, 1853-1864). It has recently been found that removal of ERRS will facilitate the incorporation of SARS-CoV-2S protein into lentivirus pseudoviruses (Ou et al 2020Nature Communications volume 11,Article number:1620).

Yu et al (2020 Science) constructed a set of prototype DNA vaccines that expressed six variants of the various deleted SARS-CoV-2S proteins with cytoplasmic tails and transmembrane domains and evaluated their immunogenicity and protective efficacy against SARS-CoV-2 virus challenge in rhesus macaques. Although soluble fragments of the extracellular domain of the SARS-CoV-2S protein caused a decrease in sgmRNA levels (indicative of viral replication), optimal protection was achieved by the full-length S protein immunogen.

The role of the transmembrane and cytoplasmic domains of the S protein in the infectivity and membrane fusion activity of SARS-CoV was studied using the SARS-CoV S pseudotyped retrovirus (SARSpp) by Broer et al (2006J.Virol. 1302-1310). SARSpp, wherein the cytoplasmic domain of S is replaced by a cytoplasmic domain from vesicular stomatitis virus G protein (VSV-G), is infectious and is up to 40% of wild type. In contrast, the infectivity of SARSpp containing both TMD and VSV-G cytoplasmic domains was severely impaired (< 5%). This shows that the TMD of S may be involved in the entry process of SARS-CoV.

Vaccination provides protection against disease by inducing an immune response in a subject against a possible pathogen prior to infection. Typically, this is accomplished by using as the immunogen an infectious agent in a live attenuated or fully inactivated form. In order to avoid the risk of using whole viruses (e.g. inactivated or attenuated viruses) as vaccines, viral proteins or subunits or recombinant forms thereof have been used as vaccines. The main obstacle to the use of natural or recombinant viral proteins as vaccine agents is to ensure that the conformation of the protein mimics its antigen in the natural environment. Suitable adjuvants, as well as in the case of peptides, carrier proteins may be used to enhance the immune response. In addition, viral proteins or subunits as vaccines may elicit a major humoral response and thus fail to elicit long lasting immunity. Subunit vaccines may be ineffective against diseases in which it may be demonstrated that complete inactivated virus may provide superior protection.

Virus-like particles (VLPs) can be used in immunogenic compositions to express viral proteins with a preferred conformation for improved antigen presentation to the immune system. VLPs are very similar to mature virions, but they do not contain viral genomic material, and they are non-replicating, which makes them safe for administration as a vaccine. In addition, VLPs can be engineered to express viral glycoproteins on the VLP surface, which are their natural physiological conformation. VLPs may be more effective than soluble envelope protein antigens in inducing neutralizing antibodies to glycoproteins, as VLPs resemble whole virus particles and are multivalent particle structures.

A variety of expression systems have been used to produce VLPs, including mammalian cell lines, bacteria, insect cell lines, yeast, and plant cells. VLPs of more than 30 different viruses have been produced in insect and mammalian systems for vaccine purposes (Noad, r.and Roy, p.,2003,Trends Microbiol11:438-44). VLPs have also been produced in plants (see WO2009/076778; WO2009/009876; WO2009/076778; WO 2010/003225; WO 2010/003235; WO2010/006452; WO2011/03522; WO 2010/148511; WO2014153674 and WO 2012/083445).

VLPs have been produced using native surface proteins from severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), S protein, M protein, E protein contained in insect cells and mammalian cells (Liu et al, 2008, j Virol, pages 11318-11330). SARS-CoV-2 virus-like particles (VLPs) have also been assembled by co-expression of viral surface proteins S, M and E in mammalian cells (Xu et al front. Bioeng. Biotechnol, 2020, 7, 30). Studies have further shown that M protein is essential for virus-like particle (VLP) formation (Siu et al Journal of Virology (2008) 82:11318-11330, huang et al Journal of Virology (2004) 78:12557-12565). In mammalian cells, the expression of membrane protein (M) and small envelope protein (E) is essential for efficient formation and release of SARS-CoV-2VLP (Xu et al front. Bioeng. Biotechnol.,2020, 7/30). Nevertheless, the minimum requirements for assembling SARS-CoV VLPs remain controversial. Huang et al (Journal of Virology (2004) 78:12557-12565) describe that VLP formation in infected human cells requires only co-expression of M and N viral proteins, whereas Siu et al (Journal of Virology (2008) 82:11318-11330) show that both E and N proteins must be co-expressed with M proteins to efficiently produce and release SARS-CoV VLPs in infected mammalian cells.

WO2012/083445 discloses the production of SARS CoV S protein in plants, wherein the transmembrane domain and cytoplasmic tail domain (TM/CT) of the S protein are replaced by TM/CT of influenza HA protein.

Several groups proposed immunization with SARS-CoV VLPs as an effective vaccine strategy. VLPs produced in insect cells or chimeric MHV/SARS-CoV VLPs produced in mammalian cells (Lokugamage et al Vaccine 2008, 2/6; 26 (6): 797-808, lu et al 2007Immunology 122496-5024) were used in these studies.

However, efficient amplification and production of SARS-CoV-2VLP in an amount that can meet the wide vaccination needs of the global population requires efficient viral structural protein and VLP production.

Disclosure of Invention

The present invention relates to modified viral structural proteins. The invention also relates to virus-like particles (VLPs) comprising modified viral structural proteins and methods of producing VLPs in a host or host cell. More specifically, the invention relates to modified coronavirus S proteins. The invention also relates to virus-like particles (VLPs) comprising modified S proteins and methods of producing VLPs in a host or host cell.

In one aspect, a modified coronavirus S protein is provided, comprising in order:

An extracellular domain derived from the coronavirus S protein;

transmembrane and cytoplasmic tail domain (TMCT), wherein the TMCT is a chimeric TMCT comprising:

a transmembrane domain (TM), wherein said TM or a portion of said TM is derived from a coronavirus S protein, and

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein.

Modified S proteins as described herein may form trimers. Thus, trimers comprising modified coronavirus S proteins as described herein are also provided.

In another aspect, there is provided a virus-like particle (VLP) comprising a modified S protein or a trimer comprising a modified S protein as described above. Thus, the VLP comprises a modified coronavirus S protein or a trimer comprising the modified S protein, the modified S protein comprising:

an extracellular domain derived from the coronavirus S protein;

The VLP may further comprise a plant lipid.

The TM may be fused directly to the CT. The TM may be derived from coronavirus S protein TM and the CT may be derived from influenza HA protein CT. Furthermore, the TM may be a chimeric TM comprising an N-terminal sequence derived from the coronavirus S protein TM and a C-terminal sequence derived from the influenza HA protein TM. The chimeric TM may include an N-terminal sequence derived from the coronavirus S protein TM, the N-terminal sequence including a sequence corresponding to SEQ ID NO:18 or SEQ ID NO:169 is at least 20 amino acids of amino acids 1-20, or corresponds to SEQ ID NO:118 or 164, or at least 21 amino acids corresponding to amino acids 1-21 of SEQ ID NO:123, at least 22 amino acids 1-22, and one or more amino acids derived from the C-terminus of the influenza HA protein TM. The one or more amino acids derived from the C-terminal end of the influenza HA protein TM may be selected from AGL or conservative substitutions of AGL, MAGL or conservative substitutions of MAGL. The chimeric TM may include a sequence corresponding to SEQ ID NO:18 from amino acids 1 to 20.

The CT may be a chimeric CT comprising an N-terminal sequence derived from the coronavirus S protein CT and a C-terminal sequence derived from the influenza HA protein CT. The chimeric CT may comprise a C-terminal sequence derived from the influenza HA protein CT, the C-terminal sequence comprising a sequence corresponding to SEQ ID NO: 18. 126, 127, 128, 129, 130 or 131, and one or more amino acids derived from the N-terminus of the coronavirus S protein CT. The one or more amino acids from the N-terminus of the coronavirus S protein CT may be selected from a conservative substitution of C or C, a conservative substitution of CC or CC, or a conservative substitution of CCM or CCM. The chimeric CT may comprise a sequence corresponding to SEQ ID NO: 18. 126, 128, 129, 130 or 131 amino acids 27-37; or SEQ ID NO:127, amino acids 27-36. In one aspect, the chimeric TMCT may comprise a chimeric TM comprising a sequence corresponding to SEQ ID NO:18 or SEQ ID NO:169, or amino acids 1-20 corresponding to SEQ ID NO:118 or SEQ ID NO:164, or amino acids corresponding to amino acids 1-21 of SEQ ID NO:123, said chimeric CT comprises amino acids corresponding to amino acids 1-22 of SEQ ID NO: 18. 126, 127, 128, 129, 130 or 131 amino acids 27-37; or a combination thereof.

The CT or a portion of the CT may comprise a sequence that hybridizes to SEQ ID NO:15, or with SEQ ID NO: 6. 8, 7, 9, 10, 12, 13 or 14, or amino acids 35-50, or amino acids identical to SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3, or amino acids 553-568, or amino acids corresponding to SEQ ID NO:18, or amino acids 22-37 of SEQ ID NO:19, or amino acids 21-40 of SEQ ID NO:37, or amino acids 21-39 of SEQ ID NO:38, or amino acids 25-36 with SEQ ID NO:39, or amino acids 24-34 with SEQ ID NO: 126. 128, 129, 130 or 131, or amino acids 22-37, or a sequence identical to SEQ ID NO:127 from 80% to 100% identity of the sequence of amino acids 22-36. The TM or a portion of the TM may comprise a sequence that is identical to SEQ ID NO:132 or 133, to 100% identity of the sequences of 132 or 133.

The TMCT may include a sequence having about 80% to about 100% identity to the sequence of seq id no: SEQ ID NO: 18. 19, 37, 38, 39, 64, 126, 127, 128, 129, 130, 131, 118, 119, 120, 123, 124, 125, 134, 135, 164, 165, 166, 169, 170, 171, 172 or 173.

The modified S protein may comprise an S1 subunit and an S2 subunit, wherein the S2 subunit comprises the chimeric TMCT.

The modified S protein may be produced as a precursor protein comprising the modified S protein and a signal peptide. The precursor proteins comprising the modified S protein and signal peptide may comprise a sequence identical to SEQ ID NO:1, or amino acids 1-1234 with SEQ ID NO:5, or amino acids 1-1234 with SEQ ID NO:21 or amino acids 1-1219 of SEQ ID NO:30, and wherein the amino acid sequence of CT comprises 80% to 100% identity to amino acids 1-1243 of SEQ ID NO:15, or with SEQ ID NO: 6. 8, 7, 9, 10, 12, 13 or 14, or amino acids 35-50, or amino acids identical to SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3 to 100% identity of the sequence of amino acids 553-568.

The signal peptide may be native or non-native to the S protein. The non-native signal peptide may be derived from a signal peptide of a Protein Disulfide Isomerase (PDI). The modified S protein may also include plant-specific N-glycans.

The CT or a portion of the CT in the modified S protein may be derived from influenza Hemagglutinin (HA) protein derived from influenza b or influenza subtype H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16. Influenza Hemagglutinin (HA) proteins may be derived from influenza b or influenza of the H1, H3, H5, H6, H7 or H9 subtype.

The extracellular domain of the modified S protein may be derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV or 229E-CoV, said TM or a portion of said TM may be derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV or 229E-CoV, or both said extracellular domain and said TM or a portion of said TM may be derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV or 229E-CoV.

In another aspect, the modified S protein may comprise one or more amino acid substitutions when compared to the wild-type coronavirus amino acid sequence. The one or more substitutions may maintain the S protein in a pre-fusion state.

The one or more amino acid substitutions may include: i) Limiting substitution of processing at the cleavage site between the S1 and S2 subunits; ii) one or more amino acid substitutions to one or more prolines, or iii) substitutions that limit processing at the cleavage site between the S1 and S2 subunits and one or more amino acid substitutions to one or more prolines.

When expressed in a host or host cell, the one or more substitutions maintain the S protein in a pre-fusion state or produce a higher yield of modified S protein when compared to the yield of the corresponding S protein expressed in the host or host cell without the one or more substitutions.

When compared with SEQ ID NO:2, the one or more amino acid substitutions may correspond to the amino acid at positions 667, 668, 670, 802, 923, 927, 971, 972, or a combination thereof.

In one aspect, the polypeptide of SEQ ID NO:2, said one or more amino acid substitutions corresponding to the amino acids at positions 971 and 972 when compared to the reference amino acid sequence. In another aspect, the polypeptide of SEQ ID NO:2, said one or more amino acid substitutions corresponding to amino acids at positions 802, 927, 971 and 972. Furthermore, the sequence corresponding to SEQ ID NO:2 may comprise one or more amino acid substitutions corresponding to amino acids at positions 667, 668, 670, or a combination thereof. Thus, the sequence corresponding to SEQ ID NO:2 may comprise substitutions corresponding to the amino acids at positions 667, 668 and 670 when compared to the reference amino acid sequence.

In one aspect, the polypeptide of SEQ ID NO:2, the one or more substitutions may correspond to the amino acids at positions 667, 668, 670, 971 and 972 when compared to the reference amino acid sequence. Corresponding to the sequence set forth in SEQ ID NO: the amino acid substitution at position 667 of 2 may be glycine or a conservative substitution of glycine, corresponding to SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to amino acid sequence of SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to SEQ ID NO:2 may be proline or a conservative substitution of proline, and corresponds to the amino acid at position 971 of SEQ ID NO: the amino acid substitution at position 972 of 2 may be proline or a conservative substitution of proline. And SEQ ID NO:2 may also include an amino acid substitution corresponding to the amino acid at position 923 when compared to the reference amino acid sequence of S protein as described above.

In another aspect, when compared to SEQ ID NO:2, the one or more amino acid substitutions may correspond to the amino acids at positions 667, 668, 670, 802, 927, 971 and 972. Corresponding to the sequence set forth in SEQ ID NO: the amino acid substitution at position 667 of 2 may be glycine or a conservative substitution of glycine, corresponding to SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to amino acid sequence of SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to amino acid position 670 of SEQ ID NO:2 may be proline or a conservative substitution of proline corresponding to the amino acid at position 802 of SEQ ID NO: the amino acid substitution at position 927 of 2 may be proline or a conservative substitution of proline, corresponding to SEQ ID NO:2 may be proline or a conservative substitution of proline, and corresponds to the amino acid at position 971 of SEQ ID NO: the amino acid substitution at position 972 of 2 may be proline or a conservative substitution of proline.

In another aspect, the polypeptide of SEQ ID NO:2 may also include an amino acid substitution corresponding to the amino acid at position 923 when compared to the reference amino acid sequence of S protein as described above. For amino acid substitutions in the modified S protein, corresponding to SEQ ID NO: the amino acid substitution at position 667 of 2 may be glycine or a conservative substitution of glycine, corresponding to SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to amino acid sequence of SEQ ID NO:2 may be serine or a conservative substitution of serine, corresponding to amino acid position 670 of SEQ ID NO:2, amino acid substitutions of amino acids at positions 802, 927, 971 and 972 may be proline or a conservative substitution of proline, and corresponds to SEQ ID NO: the amino acid substitution at position 923 of 2 may be phenylalanine or a conservative substitution of phenylalanine.

The modified S protein may have 80% to 100% identity to: SEQ ID NO: 5. 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 144, 145, 146, 155, 156, or 157, or a sequence identical to SEQ ID NO:47, amino acids 24-1259, seq ID NO:48, amino acids 25-1259, seq ID NO:49, amino acids 25-1259, seq ID NO:50, amino acids 25-1259, seq ID NO:51, amino acids 25-1259, seq ID NO:52, amino acids 25-1259, seq ID NO:53, amino acids 25-1259, seq ID NO:54, amino acids 25-1259, seq ID NO:55, amino acids 25-1259, seq ID NO:56, amino acids 25-1259, seq ID NO:57, amino acids 25-1259, seq ID NO:58, amino acids 25-1259, seq ID NO:59, amino acids 25-1262, seq ID NO:60, amino acids 25-1261, seq ID NO:61, amino acids 25-1258, or SEQ ID NO:62, amino acids 25-1256, seq ID NO:95, amino acids 25-1243, seq ID NO:96, amino acids 25-1240, seq ID NO:97, amino acids 25-1243, seq ID NO:108, amino acids 25-1341, seq ID NO:109, amino acids 25-1338, seq ID NO:110, or amino acids 25-1341 of SEQ ID NO:144, amino acids 25-1351, seq ID NO:145, amino acids 25-1348, seq ID NO:146, amino acids 25-1351, seq ID NO:155, amino acids 25-1159 of seq ID NO:156, or amino acids 25-1156 of SEQ ID NO:157 from 80% to 100% identity of amino acids 25-1159.

In another aspect, a nucleic acid is provided that includes a nucleotide sequence encoding a modified S protein as described above.

In another aspect, there is provided a composition comprising an effective dose of a modified S protein, a trimer comprising the modified S protein or a VLP comprising a modified S protein as described above, and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. In another aspect, a vaccine for inducing an immune response is provided. The vaccine comprises an effective dose of a modified S protein, a trimer comprising the modified S protein or a VLP comprising a modified S protein as described above.

The composition further comprises a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. In another aspect, a vaccine for inducing an immune response is provided. The vaccine comprises an effective dose of VLPs comprising a modified coronavirus as described above. The vaccine may be a multivalent vaccine comprising a mixture of VLPs.

In another aspect, there is provided a (non-human) host or host cell comprising a modified S protein, trimer or VLP as described above. In another aspect, there is provided a host or host cell comprising a VLP as described above. In another aspect, there is provided a composition comprising an effective dose of a VLP comprising a modified S protein as described above.

In another aspect, an S protein trimer is provided. The trimer comprises a modified coronavirus S protein comprising:

an extracellular domain derived from the coronavirus S protein;

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein. As described above, the modified S protein in the trimer may comprise one or more amino acid substitutions when compared to the wild-type coronavirus amino acid sequence. In another aspect, there is provided a composition comprising an effective dose of a trimer as described above, and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. In another aspect, there is also provided a virus-like particle (VLP) comprising a trimer as described above. The VLP may further comprise a plant lipid. In another aspect, there is provided a composition comprising an effective dose of a VLP comprising a trimer as described above, and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient. In another aspect, a vaccine for inducing an immune response is provided. The vaccine comprises an effective dose of a trimer as described above. In another aspect, a vaccine for inducing an immune response is provided. The vaccine comprises an effective dose of VLPs comprising trimers as described above. The vaccine may be a multivalent vaccine comprising a mixture of VLPs. In another aspect, a non-human host or host cell is provided that includes a trimer or VLP comprising a trimer as described above.

In another aspect, there is provided a method for inducing immunity to a coronavirus infection in a subject, the method comprising administering a composition or vaccine as described above. The composition or vaccine may be administered to the subject at one time, or the composition or vaccine may be administered to the subject multiple times. The composition or vaccine may be administered as an initial dose, and one or more subsequent doses may be administered between 1 day and 6 months from the initial dose. The subsequent dose may be administered 21 days after the initial dose is administered.

In another aspect, there is provided an antibody or antibody fragment prepared using a composition or vaccine as described above.

In another aspect, there is provided: a) A method of producing a virus-like particle (VLP) in a (non-human) host or host cell, comprising:

a) Introducing a nucleic acid comprising a nucleotide sequence encoding a modified S protein as described above into a non-human host or host cell; or a non-human host or host cell comprising a nucleic acid comprising a nucleotide sequence encoding a modified S protein as described above, and

b) Culturing the non-human host or host cell under conditions that allow expression of the nucleic acid, thereby producing the VLP.

In a further step c), the non-human host or host cell may be harvested.

In another aspect, there is provided: b) A method of increasing the production yield of coronavirus S protein in a (non-human) host or host cell comprising:

a) Introducing a nucleic acid comprising a nucleotide sequence encoding a modified S protein as described above into a non-human host or host cell; or providing a non-human host or host cell comprising a nucleic acid comprising a nucleotide sequence encoding a modified S protein as described above; and

b) Culturing the non-human host or host cell under conditions that allow expression of the modified S protein encoded by the nucleic acid, thereby producing the modified S protein in higher yields as compared to a host or host cell that expresses an unmodified S protein under similar or identical conditions.

In a further step c), the non-human host or host cell may be harvested.

In another aspect, there is provided C) a method of increasing the yield of production of virus-like particles (VLPs) in a (non-human) host or host cell, comprising:

a) Introducing a nucleic acid encoding a modified coronavirus S protein into a non-human host or host cell, the modified coronavirus S protein comprising:

An extracellular domain derived from the coronavirus S protein;

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein;

providing a non-human host or host cell comprising a nucleic acid encoding a modified S protein comprising:

an extracellular domain derived from the coronavirus S protein;

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein; and

b) Culturing the non-human host or host cell under conditions that allow expression of the modified S protein encoded by the nucleic acid, thereby producing VLPs comprising the modified S protein in higher yields than VLPs in a host of a host cell that expresses unmodified S protein under similar or identical conditions.

In another aspect, there is provided D) a method of producing a virus-like particle (VLP) in a (non-human) host or host cell, comprising:

an extracellular domain derived from the coronavirus S protein;

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein; or (b)

an extracellular domain derived from the coronavirus S protein;

In another aspect, the VLP of method a), B), C) or D) may also be extracted and purified from the host or host cell. The host or host cell may include a plant, plant cell, fungus, fungal cell, insect cell, animal or animal cell. The host or host cell of method A), B), C) or D) may be a plant, plant part or plant cell.

In another aspect, there is provided a VLP produced by the method of a), B), C) or D).

Furthermore, in another aspect, there is provided a composition comprising an adjuvant and a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified S protein comprising:

an extracellular domain derived from the coronavirus S protein;

a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein, and wherein the amino acid sequence of SEQ ID NO:2, the modified S protein further comprises substitutions at positions 667, 668, 670, 971 and 972 when compared to the reference amino acid sequence shown.

In another aspect, there is provided a composition comprising a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified S protein comprising:

an extracellular domain derived from the coronavirus S protein;

cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from influenza Hemagglutinin (HA) protein; and wherein the modified S protein comprises a glycine substitution at position 667, a serine substitution at position 668, a serine substitution at position 670, a proline substitution at position 971, and a proline substitution at position 972, said positions corresponding to SEQ ID NO:2, and a reference amino acid sequence. The influenza Hemagglutinin (HA) protein may be derived from influenza b or influenza of subtype H1, H3, H5, H6, H7 or H9. The composition may further comprise an adjuvant.

In another aspect, there is provided a composition comprising a virus-like particle (VLP) comprising a modified coronavirus S protein comprising the amino acid sequence of SEQ ID NO: 21. The composition may further comprise an adjuvant.

This summary does not necessarily describe all features of the invention.

Drawings

These and other features of the present invention will become more apparent from the following description, in which reference is made to the accompanying drawings, in which:

FIG. 1 shows a schematic representation of the coronavirus S protein and the positions of the S1/S2 (aa 685/686) and S2' cleavage sites. SP: signal peptide (aa 1-15); NTD: an N-terminal domain (aa 16-306); RBD: receptor binding domain (aa 335-527); FP: fusion peptide (aa 816-833); HR1: heptad repeat 1 (aa 908-991); HR2: heptad repeat 2 (aa 1166-1207); TM: transmembrane domain (aa 1214-1234); CT: cytoplasmic tail (aa 1235-1273). The residue number (aa) of each region corresponds to their position in the S protein of SARS-CoV-2 (2019-nCoV).

Figure 2 shows an alignment of amino acid sequences from an exemplary influenza strain. The C-terminal region of the extracellular domain, the transmembrane domain (TM) and the cytoplasmic tail domain (CT) of Hemagglutinin (HA) are shown below: h1 A/California/07/2009 (SEQ ID NO: 6), H2A/Singapore/1/1957HA (SEQ ID NO: 7), H3A/Minnesota/41/2019 HA (SEQ ID NO: 8), H5A/Indonesia/5/05 HA (SEQ ID NO: 9), H6A/Teal/Hong Kong/W312/97HA (SEQ ID NO: 10), H7A/Guangdong/17 SF003/2016HA (SEQ ID NO: 11), H9A/Hong Kong/1073/99HA (SEQ ID NO: 12), and B/Washington/02/2019HA (SEQ ID NO: 13). The consensus sequence of these sequences is also shown (SEQ ID NO: 14).

Figure 3A shows expression in plants under the control of the following 5' utrs: quantitative fold change differences in accumulation of SARS-CoV-2S protein having a native (wild-type) transmembrane domain and cytoplasmic tail (wtTMCT) of SARS-CoV-2S protein: nbMT78 (construct 8586), nbCSY65 (construct 8589), and nbHEL40 (construct 8591); a modified SARS-CoV-2 protein in which the native (wild-type) transmembrane domain and cytoplasmic tail (wtTMCT) have been replaced by TMCT of influenza Hemagglutinin (HA) of influenza H5A/Indonesia/5/05 (H5 ittmct) under the control of nbMT78 (construct 8592), nbCSY65 (construct 8595) and nbHEL40 (construct 8597); and modified SARS-CoV-2 protein, wherein the natural (wild-type) cytoplasmic tail (wtCT) HAs been replaced by the CT of influenza Hemagglutinin (HA) of influenza H5A/Indonesia/5/05 (H5 iTMCT) under the control of nbMT78 (construct 8610), nbcSY65 (construct 8611) and nbHEL40 (construct 8671). The SARS-CoV-2S protein sequence (called nCOV S (GSAS-2P)) has the following substitutions: relative to SEQ ID NO:2, R667G, R668S, R670S, K971P and V972P. The results have been normalized to SARS-CoV-2S protein accumulation from construct 8591 (which is set to 1). FIG. 3B shows protein separation of clarified crude extract on non-reducing SDS-PAGE gels. The following modified S proteins are expressed in plants: lane 1: under the control of nbMT78, an S protein with a wild-type transmembrane and cytoplasmic tail domain (wt TMCT); lane 2: under control of nbCSY65, an S protein with wild-type transmembrane and cytoplasmic tail domain (wt TMCT); lane 3: under the control of nbHEL40, an S protein with a wild-type transmembrane and cytoplasmic tail domain (wt TMCT); lane 4: a modified S protein having a SARS-CoV-2 extracellular domain and a transmembrane and cytoplasmic tail domain from Hemagglutinin (HA) of H5A/Indonesia/5/05 (H5 i TMCT) under the control of nbMT 78; lane 5: a modified S protein having a SARS-CoV-2 extracellular domain and a transmembrane and cytoplasmic tail domain from Hemagglutinin (HA) of H5A/Indonesia/5/05 (H5 i TMCT) under control of nbCSY 65; lane 6: a modified S protein having a SARS-CoV-2 extracellular domain and a transmembrane and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 i TMCT) under the control of nbHEL 40; lane 7: a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and a cytoplasmic tail domain (CT) of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 i CT) under the control of nbMT 78; lane 8: a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and a cytoplasmic tail domain (CT) of Hemagglutinin (HA) from influenza H5A/Indonesia/5/05 (H5 i CT) under control of nbCSY 65; lane 9: a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and a cytoplasmic tail domain (CT) of Hemagglutinin (HA) from influenza H5A/Indonesia/5/05 (H5 iCT) under the control of nbHEL 40. The modified S protein has a molecular weight of about 150kDa and is indicated by the arrow. FIG. 3C shows immunoblot analysis of the same series of lysates shown in FIG. 3B, with lanes corresponding to those depicted in FIG. 3B. The upper panel shows the detection using an anti-SARS-CoV-2S 1 antibody (40150-R007). The lower panel shows the detection using an anti-SARS-CoV-2S 2 antibody (NB 100-56578). Monomers of the SARS-CoV-2 protein (including the S1 and S2 subunits) have a molecular weight (non-reducing) of about 150 kDa.

FIG. 4A shows the quantitative fold change differences in SARS-CoV-2S protein accumulation in plants expressing: a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo); a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H1A/California/7/2009 (H1 California); a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H3A/Minnesota/41/2019 (H3 Minnesota); modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H6A/Teal/Hong Kong/W312/97 (H6 Hong Kong); a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H7A/Guangdong/17 SF003/2016 (H7 Guangdong); a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from H9A/Hong Kong/1073/99 (H9 Hong Kong); and modified S proteins having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane, and a cytoplasmic tail domain of Hemagglutinin (HA) from B/Washington/02/2019 (B Washington). Results have been normalized to the accumulation of SARS-CoV-2S protein from construct 8671 encoding the modified SARS-CoV-2 protein (which was set to 1), where the natural (wild-type) cytoplasmic tail (wtCT) HAs been replaced by CT of influenza Hemagglutinin (HA) of influenza H5A/Indonesia/5/05 (H5 iCT) under the control of nbHEL40 (H5 Indo). Figure 4B shows immunoblot analysis of crude lysates from plants expressing modified S protein from the following constructs: lane 2, modified S protein with SARS-CoV-2 extracellular domain, SARS-CoV-2 transmembrane and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo); lane 3, modified S protein with SARS-CoV-2 extracellular domain, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from H1A/California/07/2009 (H1 Calif); lane 4, modified S protein with SARS-CoV-2 extracellular domain, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from H3A/Minnesota/41/2019 (H3 Minn); lane 5, modified S protein with the extracellular domain of SARS-CoV-2, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from H6A/Teal/Hong Kong/W312/97 (H6 HK); lane 6, modified S protein with SARS-CoV-2 extracellular domain, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from H7A/Guangdong/17 SF003/2016 (H7 Guan); lane 7, modified S protein with the extracellular domain of SARS-CoV-2, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from H9A/Hong Kong/1073/99 (H9 HK); lane 8, modified S protein with SARS-CoV-2 extracellular domain, SARS-CoV-2 transmembrane, cytoplasmic tail domain of Hemagglutinin (HA) from B/Washington/02/2019 (B Wash). Lane 1 is crude lysate from plants infiltrated with agrobacterium empty. The Sino 400150-R007 antibody was used to detect the S1 subunit of SARS-COV-2S protein. Monomers of the SARS-CoV-2 protein (including the S1 and S2 subunits) have a molecular weight (non-reducing) of about 150 kDa. FIG. 4C shows immunoblot analysis of the same series of lysates shown in FIG. 4B, except that the NB100-56578 antibody was used to detect the S2 subunit of SARS-COV-2S protein.

Fig. 5A shows the following amino acid sequences: the C-terminal region of the native SARS-CoV-2S protein (wtTM/wtCT), the C-terminal region of influenza H5 Hemagglutinin (HA) (H5 iTM/H5 iCT), the C-terminal region of the modified SARS-CoV-2S protein having a wild-type transmembrane domain (TM) and an influenza H5 HA Cytoplasmic Tail (CT) domain (wtTM/H5 iCT), and the C-terminal region of the modified S protein (wtTM/H5 iCT V1-V4) having a variable edge between the SARS-CoV-2 Transmembrane (TM) domain and the H5A/Indenosia/5/05 HA Cytoplasmic Tail (CT) domain. TM domains from coronavirus S protein are underlined and CT domains derived from influenza HA are shown in bold. FIG. 5B shows the quantitative fold change differences in SARS-CoV-2S protein accumulation in plants expressing each of the four variant modified S proteins with chimeric transmembrane domain (TM) and cytoplasmic tail domain (TMCT) relative to modified SARS-CoV-2S protein accumulation in plants expressing modified SARS-CoV-2S proteins with chimeric TMCT with wild-type transmembrane domain (TM) and influenza H5 HA Cytoplasmic Tail (CT), set to 1, as shown in FIG. 5A (wtTM/H5 iCT, V1-V4).

FIG. 6A shows an electron micrograph of a virus-like particle (VLP) comprising SARS-CoV-2S protein having a wild-type transmembrane and cytoplasmic tail domain (wtTMCT; construct 8591). Fig. 6B shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain and an influenza H5 hemagglutinin transmembrane domain and a cytoplasmic tail domain (H5 i TMCT; construct 8597). FIG. 6C shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H5 hemagglutinin cytoplasmic tail domain (H5 iCT; construct 8671). FIG. 6D shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein with an alternative form of SARS-CoV-2 extracellular domain and chimeric transmembrane and cytoplasmic tail domain (TMCT) (H5 i CT V1; construct 8980). FIG. 6E shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein (H5 i CT V2; construct 8981) with an alternative form of SARS-CoV-2 extracellular domain and chimeric transmembrane and cytoplasmic tail domain (TMCT). FIG. 6F shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein (H5 iCT V3; construct 8982) having an alternative form of SARS-CoV-2 extracellular domain with a SARS-CoV-2 extracellular domain and a chimeric transmembrane and cytoplasmic tail domain (TMCT). FIG. 6G shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein (H5 i CT V4; construct 8983) with an alternative form of SARS-CoV-2 extracellular domain and chimeric transmembrane and cytoplasmic tail domain (TMCT). FIG. 6H shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H1 hemagglutinin cytoplasmic tail domain (H1 CT; construct 7390). FIG. 6I shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H3 hemagglutinin cytoplasmic tail domain (H3 CT; construct 7391). FIG. 6J shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H6 hemagglutinin cytoplasmic tail domain (H6 CT; construct 7392). FIG. 6K shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H7 hemagglutinin cytoplasmic tail domain (H7 CT; construct 7393). FIG. 6L shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza H9 hemagglutinin cytoplasmic tail domain (H9 CT; construct 7394). FIG. 6M shows an electron micrograph of a virus-like particle (VLP) comprising a modified S protein having a SARS-CoV-2 extracellular domain, a SARS-CoV-2 transmembrane domain, and an influenza HA B hemagglutinin cytoplasmic tail domain (HA B CT; construct 7395).

Fig. 7A shows a schematic diagram of a receptor carrier 8501. Fig. 7B shows a schematic diagram of a recipient carrier 8500. Fig. 7C shows a schematic diagram of a receptor carrier 8716.

Fig. 8A shows a schematic view of a carrier 8586. Fig. 8B shows a schematic view of a carrier 8589. Fig. 8C shows a schematic view of the carrier 8591.

Fig. 9A shows a schematic view of the carrier 8592. Fig. 9B shows a schematic view of the carrier 8595. Fig. 9C shows a schematic view of the carrier 8597.

Fig. 10A shows a schematic view of a carrier 8610. Fig. 10B shows a schematic view of the carrier 8611. Fig. 10C shows a schematic view of the carrier 8671.

FIG. 11A shows the quantitative fold change accumulated in plants expressing modified SARS-CoV-2S protein (wtTM/H5 iCT) with other substitutions. The modified SARS-CoV-2S protein has the following substitutions: "GSAS-2P": R667G, R668S, R670S, K971P and V972P; "GSAS-4P": R667G, R668S, R670S, K971P, V972P, F802P and a927P; "GSAS-6P": R667G, R668S, R670S, K971P, V972P, F802P, A877P, A884P and A927P (relative to the reference sequence of SEQ ID NO: 2). The results have been normalized to the accumulation of modified SARS-CoV-2 (wtTM/H5 iCT) and GSAS+2P substitutions (which were set to 1). FIG. 11B shows the quantitative fold change accumulated in plants expressing modified SARS-CoV-2S proteins (wtTM/H5 iCT) having GSAS-2P, GSAS-4P and GSAS-6P substitutions, respectively, as described in FIG. 11A, as compared to the cumulative quantitative fold change in which each modified SARS-CoV-2S protein further introduced the L923F substitution. The results have been normalized to the accumulation of modified SARS-CoV-2 (wtTM/H5 iCT) and GSAS+2P substitutions (which were set to 1).

Fig. 12A shows a schematic view of carrier 8980. Fig. 12B shows a schematic view of carrier 8981. Fig. 12C shows a schematic view of carrier 8982. Fig. 12D shows a schematic view of carrier 8983.

Fig. 13A shows a schematic diagram of carrier 7390. Fig. 13B shows a schematic view of carrier 7391. Fig. 13C shows a schematic view of carrier 7392. Fig. 13D shows a schematic view of carrier 7393. Fig. 13E shows a schematic diagram of carrier 7394. Fig. 13F shows a schematic diagram of carrier 7395.

Fig. 14A shows a schematic view of carrier 8953. Fig. 14B shows a schematic view of carrier 8940.

Fig. 15A shows a schematic view of carrier 8933. Fig. 15B shows a schematic view of carrier 8960. Fig. 15C shows a schematic view of carrier 8947.

Figure 16A shows immunoblot analysis of crude lysates from plants expressing modified S protein from the following constructs: lane 1, modified S protein with SARS-CoV-1 extracellular domain, transmembrane and cytoplasmic tail domain ("wtTMCT", construct 9231); lane 2, modified S protein with the extracellular domain from SARS-CoV-1, transmembrane and cytoplasmic tail domain (TMCT) from Hemagglutinin (HA) of H5A/Indonesia/5/05 ("H5 ittct", construct 9232); lane 3, modified S protein with extracellular and transmembrane domains from SARS-CoV-1 and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo) ("H5 iCT", construct 9233); lane 4, modified S protein with extracellular and transmembrane domains from SARS-CoV-1 and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo) (with variable edge between SARS-CoV-1 Transmembrane (TM) domain and H5A/Indonesia/5/05 HA Cytoplasmic Tail (CT) domain) ("H5 iCT (V4)", construct 9234); lane 5, modified S protein with extracellular and transmembrane domains from SARS-CoV-1 and cytoplasmic tail domain of Hemagglutinin (HA) from H1A/California/7/2009 ("H1 cCT", construct 9235). The first antibody used for detection was the SARS-CoV spike S1 subunit antibody from Sino Biologicals (40150-MM 08, 1/5000). The secondary antibody used for detection was goat anti-mouse antibody from JIR (115-035-146,1/10000). The modified S protein has a molecular weight of about 150 kDa.

Fig. 16B, 16C and 16D show immunoblot analysis of fractions F5 (30%), F6 (30%), F7 (25%), F8 (25%), F9 (25%), F10 (15%) and F11 (15%) from discontinuous iodixanol density gradients. Accumulation of proteins in these fractions indicates the formation of higher molecular weight structures, i.e., VLP formation. For immunoblotting of fractions from crude lysates, the first antibody used for detection was SARS-CoV spike S1 subunit antibody from Sino Biologicals, 40150-MM08 (1/5000), and the second antibody used for detection was goat anti-mouse antibody, JIR,115-035-146 (1/10000). Fig. 16B: crude lysates from plants expressing the SARS-CoV-1S protein (with 2P+R667A substitutions) with the native TMCT domain (wtTMCT, construct 9231) were analyzed. Fig. 16C: crude lysate from plants expressing modified SARS-CoV-1S protein (with 2P+R667A substitutions) with TMCT from H5A/Indonesia/5/05HA (H5 iTMCT, construct 9232). Fig. 16D: crude lysate from plants expressing modified SARS-CoV-1S protein (with 2P+R667A substitutions) with cytoplasmic tail from H5A/Indonesia/5/05HA (H5 iCT, construct 9233).

Figure 17A shows an electron micrograph of a virus-like particle (VLP) comprising SARS-COV-1S protein (with 2p+r667a substitutions) with a native TMCT domain (wtTMCT, construct 9231). Figure 17B shows an electron micrograph of a virus-like particle (VLP) comprising a modified SARS-CoV-1S protein (with 2p+r667a substitutions) with TMCT (H5 ittmct, construct 9232) from H5A/Indonesia/5/05 HA. Figure 17C shows an electron micrograph of a virus-like particle (VLP) comprising a modified SARS-CoV-1S protein (with 2p+r667a substitutions) with cytoplasmic tail from H5A/Indonesia/5/05HA (H5 iCT, construct 9233).

Fig. 18A shows a schematic view of carrier 9231. Fig. 18B shows a schematic view of carrier 9232. Fig. 18C shows a schematic view of carrier 9233. Fig. 18D shows a schematic view of carrier 9234. Fig. 18E shows a schematic view of carrier 9235.

Figure 19A shows immunoblot analysis of crude lysates from plants expressing modified S protein from the following constructs: lane 1, modified S protein with MERS-CoV extracellular domain, transmembrane and cytoplasmic tail domain ("wtTMCT", construct 9246); lane 2, modified S protein with extracellular domain from MERS-CoV ("H5 ittmct", construct 9247) from transmembrane and cytoplasmic tail domain (TMCT) of Hemagglutinin (HA) from H5A/Indonesia/5/05; lane 3, modified S protein with extracellular and transmembrane domains from MERS-CoV and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo) ("H5 iCT", construct 9249); lane 4, modified S protein with extracellular and transmembrane domains from MERS-CoV and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo) (with variable edges between MERS-CoV Transmembrane (TM) domain and H5A/Indonesia/5/05HA Cytoplasmic Tail (CT) domain) ("H5 iCT (V4)", construct 9250); lane 5, modified S protein with extracellular and transmembrane domains from MERS-CoV and cytoplasmic tail domain of Hemagglutinin (HA) from H1A/California/7/2009 ("H1 cCT", construct 9251). The primary antibody used for detection was the MERS-CoV spike protein S1 antibody from Sino Biological (N-terminal) (100208-RP 02, 1/5000). The second antibody used for detection was a goat anti-mouse antibody from JIR (115-035-144,1/10000). The modified S protein has a molecular weight of about 175 kDa. Fig. 19B shows an electron micrograph of a virus-like particle (VLP) comprising MERS-COV S protein with native TMCT domain (with asvg+2p substitution) (wtTMCT, construct 9246). Fig. 19C shows an electron micrograph of a virus-like particle (VLP) comprising a modified MERS-CoV S protein (with asvg+2p substitution) with TMCT from H5A/Indonesia/5/05HA (H5 ittmct, construct 9247). Fig. 19D shows an electron micrograph of a virus-like particle (VLP) comprising a modified MERS-CoV S protein with cytoplasmic tails from H5A/Indonesia/5/05HA (with asvg+2p substitutions) (H5 iCT, construct 9249). Fig. 19E shows an electron micrograph of a virus-like particle (VLP) comprising a modified MERS-CoV S protein (with asvg+2p substitutions) (H5 iCT (V4), construct 9250) with cytoplasmic tail from H5A/Indonesia/5/05HA (variable edge between MERS-CoV Transmembrane (TM) domain and H5A/Indonesia/5/05HA Cytoplasmic Tail (CT) domain). Fig. 19F shows an electron micrograph of a virus-like particle (VLP) comprising a modified MERS-CoV S protein (with asvg+2p substitutions) with cytoplasmic tails from H1A/California/7/2009 HA (H1 cCT, construct 9251).

Fig. 20A shows a schematic view of the carrier 9246. Fig. 20B shows a schematic view of the carrier 9247. Fig. 20C shows a schematic view of the carrier 9249. Fig. 20D shows a schematic view of the carrier 9250. Fig. 20E shows a schematic view of the carrier 9251.

Fig. 21 shows a schematic diagram of the receptor carrier 7147.

FIG. 22 shows an alignment of the native SARS-CoV-2, SARS-CoV-1 and MERS-CoV S protein sequences (SEQ ID NOS: 2, 114 and 115) with the native signal peptide removed. Residues corresponding to each of RRAR furin cleavage site (667-670) and F802P, A877P, A884P, A927P, K971P, V972P in the native SARS-CoV-2S protein without signal peptide (SEQ ID NO: 2) are boxed with homologous residues from the native SARS-CoV-1S protein without signal peptide (SEQ ID NO: 114) and the native MERS S protein (SEQ ID NO: 115).

Figure 23A shows immunoblot analysis of crude lysates from plants expressing modified S protein from the following constructs: lane 3, modified S protein with OC43-CoV extracellular domain, transmembrane and cytoplasmic tail domain ("wtTMCT", construct 9269); lane 4, modified S protein with extracellular domain from OC43-CoV ("H5 ittct", construct 9270) from transmembrane and cytoplasmic tail domain (TMCT) of Hemagglutinin (HA) from H5A/Indonesia/5/05; lane 5, modified S protein with extracellular and transmembrane domains from OC43-CoV ("H5 iCT", construct 9272) from cytoplasmic tail domain of Hemagglutinin (HA) of H5A/Indonesia/5/05 (H5 Indo); lane 6, modified S protein with extracellular and transmembrane domains from OC43-CoV and cytoplasmic tail domain of Hemagglutinin (HA) from H5A/Indonesia/5/05 (H5 Indo) (with variable edge between OC43-CoV Transmembrane (TM) domain and H5A/Indonesia/5/05 HA Cytoplasmic Tail (CT) domain) ("H5 iCT (V4)", construct 9273); lane 7, modified S protein with extracellular and transmembrane domains from OC43-CoV and cytoplasmic tail domain of Hemagglutinin (HA) from H1A/California/7/2009 ("H1 cCT", construct 9274). The primary antibody used for detection was anti-coronavirus OC43 spike protein from Antibodies-online (ABIN 2754654, 1/1000). The second antibody used for detection was a goat anti-rabbit antibody from JIR (111-035-144,1/10000). The modified S protein has a molecular weight of about 150 kDa. FIG. 23B shows an electron micrograph of a virus-like particle (VLP) comprising a modified OC43-CoV S protein with TMCT from H5A/Indonesia/5/05 HA (with GGSGS+2P substitution) (H5 iTMCT, construct 9270). Fig. 23C shows an electron micrograph of a virus-like particle (VLP) comprising a modified OC43-CoV S protein (with ggsgs+2p substitution) with cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 iCT, construct 9272). FIG. 23D shows an electron micrograph of a virus-like particle (VLP) comprising a modified OC43-CoV S protein (with GGSGS+2P substitution) (H5 iCT (V4), construct 9273) with cytoplasmic tail from H5A/Indonesia/5/05 HA (variable edge between OC43-CoV Transmembrane (TM) domain and H5A/Indonesia/5/05 HA Cytoplasmic Tail (CT) domain). Fig. 23E shows an electron micrograph of a virus-like particle (VLP) comprising a modified OC43-CoV S protein (with ggsgs+2p substitution) with cytoplasmic tail from H1A/California/7/2009 HA (H1 cCT, construct 9274).

Fig. 24A shows a schematic view of the carrier 9269. Fig. 24B shows a schematic view of the carrier 9270. Fig. 24C shows a schematic view of the carrier 9272. Fig. 24D shows a schematic view of the carrier 9273. Fig. 24E shows a schematic view of the carrier 9274.

FIG. 25A shows an electron micrograph of a virus-like particle (VLP) comprising 229E-CoV S protein with native TMCT domain (with R567A+2P substitution) (wtTMCT, construct 9310). FIG. 25B shows an electron micrograph of a virus-like particle (VLP) comprising a modified 229E-CoV S protein (with R567A+2P substitution) with TMCT from H5A/Indonesia/5/05 HA (H5 iTMCT, construct 9311). FIG. 25C shows an electron micrograph of a virus-like particle (VLP) comprising a modified 229E-CoV S protein (with R567A+2P substitution) with cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 iCT, construct 9312). FIG. 25D shows an electron micrograph of a virus-like particle (VLP) comprising a modified 229E-CoV S protein (with R567A+2P substitutions) with cytoplasmic tail from H5A/Indonesia/5/05 HA, with a variable edge between the 229E-CoV Transmembrane (TM) domain and the H5A/Indonesia/5/05 HA Cytoplasmic Tail (CT) domain (H5 iCT (V4), construct 9313). Figure 25E shows an electron micrograph of a virus-like particle (VLP) with a modified 229E-CoV S protein (with R567a+2p substitution) from the cytoplasmic tail of H1A/California/7/2009 HA (H1 cCT, construct 9314).

Fig. 26A shows a schematic diagram of the carrier 9310. Fig. 26B shows a schematic view of the carrier 9311. Fig. 26C shows a schematic diagram of the carrier 9312. Fig. 26D shows a schematic view of the carrier 9313. Fig. 26E shows a schematic diagram of the carrier 9314.

Detailed Description

The following description is of the preferred embodiments.

As used herein, the terms "comprises," "comprising," "has," "including," "contains," "containing" and grammatical variations thereof are inclusive or open-ended and do not exclude other, unrecited elements and/or method steps. When used in connection with a method or process herein, the term "consisting essentially of … …" means that other elements and/or process steps may be present, but that such additions do not materially affect the recited method or manner of operation. The term "consisting of … …" when used in conjunction with a use or method herein excludes the presence of other elements and/or method steps. In certain embodiments, the use or method described herein as comprising certain elements and/or steps may also consist essentially of, and in other embodiments consist of, those elements and/or steps, whether or not such embodiments are specifically mentioned. In addition, the use of the singular includes the plural and unless otherwise indicated, "or" means "and/or". The term "plurality" as used herein means more than one, e.g., two or more, three or more, four or more, etc. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. As used herein, the term "about" refers to a deviation of about +/-10% from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically mentioned. When used herein in connection with the term "comprising," the use of the word "a" or "an" may mean "one" but it is also consistent with the meaning of "one or more," at least one, "and" one or more than one.

The present invention relates to modified viral structural proteins and their production in a host or host cell. The modified viral structural proteins include, in order, an extracellular domain, a transmembrane domain (TM) or a portion of TM, and a Cytoplasmic Tail (CT) domain or a portion of CT, wherein the extracellular domain and the portion of TM or TM are derived from the family coronaviridae and the portion of CT or CT is derived from influenza Hemagglutinin (HA) protein.

The modified viral structural protein may be a modified coronavirus structural protein in which the cytoplasmic tail domain or a portion of the cytoplasmic tail domain HAs been replaced with the cytoplasmic tail domain or a portion of the cytoplasmic tail domain of an influenza Hemagglutinin (HA) protein. For example, the modified viral structural protein may be a modified coronavirus spike or surface (S) protein, wherein the cytoplasmic tail domain or a portion of the cytoplasmic tail domain of the S protein HAs been replaced with the cytoplasmic tail domain or a portion of the cytoplasmic tail domain of an influenza Hemagglutinin (HA) protein.

The present disclosure provides modified viral structural proteins, wherein the extracellular domain and transmembrane domain of the modified viral structural protein may be derived from the extracellular domain and transmembrane domain of a coronavirus S protein, and wherein the cytoplasmic tail domain is derived from the cytoplasmic tail domain of an influenza Hemagglutinin (HA) protein.

The modified S protein may be a chimeric modified S protein or a chimeric S protein. "chimeric S protein" refers to a protein or polypeptide that includes amino acid sequences and/or protein domains or portions of protein domains from two or more sources fused as a single polypeptide. For example, but not limited to, the extracellular domain and transmembrane domain (TM) or a portion of TM of the chimeric S protein may be derived from a first viral structural protein, e.g., coronavirus S protein, and the Cytoplasmic Tail (CT) or a portion of CT may be derived from a second viral structural protein, e.g., CT may be derived from influenza HA. Furthermore, the extracellular domain may be derived from a first viral structural protein, e.g., a first coronavirus S protein, the TM or a portion of the TM may be derived from a second viral structural protein, e.g., a second coronavirus S protein, and CT or a portion of the CT may be derived from a third viral structural protein, e.g., the CT may be derived from influenza HA. Thus, the modified S protein or chimeric S protein may include chimeric transmembrane and cytoplasmic tail domains (TMCT).

The modified coronavirus S protein may in turn comprise

An extracellular domain derived from the coronavirus S protein;

Transmembrane and cytoplasmic tail domain (TMCT), wherein the TMCT may be a chimeric TMCT, which may comprise:

a transmembrane domain (TM), wherein said TM or a portion of said TM may be derived from a coronavirus S protein, and

The TM or a portion of TM may be directly fused or joined to the CT or portion of CT, or the TM or portion of TM may be fused or joined to the CT or portion of CT via an intervening peptide sequence.

Furthermore, the TM may be a chimeric TM that may comprise an N-terminal sequence derived from the coronavirus S protein TM and a C-terminal sequence derived from the influenza HA protein TM. The CT may be a chimeric CT that may comprise an N-terminal sequence derived from the coronavirus S protein CT and a C-terminal sequence derived from the influenza HA protein CT.

Thus, chimeric TMCT may include native coronavirus S protein TM, chimeric coronavirus S protein/influenza HA TM, native influenza HA CT, chimeric influenza HA/coronavirus S protein CT, or a combination thereof. Chimeric coronavirus S protein/influenza HA TM comprises the sequence of a TM derived from coronavirus S protein and the sequence of a TM derived from influenza HA. Similarly, chimeric influenza HA/coronavirus S protein CT comprises the sequence of CT derived from influenza HA and the sequence of CT derived from coronavirus S protein.

"chimeric transmembrane and cytoplasmic tail domain" or "chimeric TMCT" refers to TMCT that is not native to the coronavirus S protein TMCT. Chimeric TMCT includes sequences that are not found in nature. Thus, TMCT may include sequences heterologous to the extracellular domain of the coronavirus S protein. The term "heterologous" refers to a sequence or domain derived from a different biological or synthetic source. For example, chimeric TMCT may comprise a TM or a portion of a TM derived from the same coronavirus S protein as the extracellular domain, i.e., the TM may be homologous to the extracellular domain of the S protein, or a portion of a TM or a TM may be derived from a different viral TM, e.g., a TM derived from a coronavirus S protein that is different from the extracellular domain, i.e., the TM may be heterologous to the extracellular domain of the S protein. The CT or a portion of the CT may be derived from CT heterologous to the extracellular domain, TM or both the extracellular domain and TM of the modified S protein.

The coronavirus S protein, modified S protein, or extracellular domain and transmembrane domain or portion of a transmembrane domain of modified coronavirus S protein may be derived from any member of the coronaviridae family of viruses. For example, the coronavirus S protein, modified S protein, or extracellular domain and transmembrane domain of modified coronavirus S protein (for example) may be derived from a coronavirus, such as an alpha-coronavirus (alpha-CoV), beta-coronavirus (beta-CoV), gamma-coronavirus (gamma-CoV), or delta-coronavirus (delta-CoV). For example, the coronavirus may be an alpha-coronavirus (alpha-CoV) or a beta-coronavirus (beta-CoV). The alpha-coronavirus may be a Duvinacorus subgenera virus, such as, for example, HCoV-229E (229E-CoV), or may be a Setracovirus subgenera virus, such as, for example, HCoV-NL63. In a preferred embodiment, the coronavirus is a β -coronavirus (β -CoV). The beta coronavirus may be a lineage Abeta coronavirus, such as, for example, HCoV-OC43 (OC 43-CoV) or HCoV-HKU1 (HKU 1-CoV), a lineage Abeta coronavirus, such as, for example, SARS-CoV (also known as SARS-CoV-1) or SARS-CoV-2, and variants thereof, or a lineage Cbeta coronavirus, such as, for example, MERS-CoV.

The coronavirus S protein, modified S protein or extracellular domain, and the transmembrane domain or portion of the transmembrane domain of the modified coronavirus S protein may also be derived from variants of the SARS-CoV-2 lineage, including, but not limited to, strain B.1.1.7 ("alpha" variants) (20I/501Y.V1, MW531680.1), strain B.1.351 ("beta" variants) (20H/501Y.V2), strain P.1 ("gamma" variants) (20J/501Y.V3), strain B1.617.2 ("delta" variants), strain B.1.525, strain B.1.429 ("ETA" variants), or other variants including naturally occurring mutant strains in the coronavirus S protein, or naturally occurring recombinant strains thereof.

In one embodiment, the extracellular domain and the transmembrane domain or a portion of the transmembrane domain of the modified viral structural protein are derived from spike proteins of coronaviruses of the SARS-CoV-2 lineage (also known as SARS-CoV-2 variants). In other embodiments, the extracellular domain and the transmembrane domain or a portion of the transmembrane domain of the modified viral structural protein are derived from the spike protein (S) of SARS-CoV-1, MERS-CoV, OC43-CoV or 229E-CoV or variants thereof.

For the modified viral structural protein, the term "modified" as used herein may refer to the replacement of a cytoplasmic tail domain (CT) or a portion of CT in a structural protein from the family coronaviridae with a CT or a portion of CT of a heterologous virus. For example, the modified viral structural protein may be a coronavirus S protein, wherein CT or a portion of CT of the S protein HAs been replaced with CT or a portion of CT of influenza Hemagglutinin (HA).

Thus, the modified viral structural protein may be a modified coronavirus spike (S) protein comprising a transmembrane domain (TM) or a portion of TM and a Cytoplasmic Tail (CT) or a portion of CT, wherein the CT or portion of CT may be derived from influenza Hemagglutinin (HA) protein, and wherein the TM or portion of TM is heterologous to the CT or portion of CT. Furthermore, the modified S protein comprises a transmembrane domain (TM) or a portion of TM and a Cytoplasmic Tail (CT) or a portion of CT, wherein the CT or portion of CT may be derived from influenza Hemagglutinin (HA) protein, and wherein the CT or portion of CT is heterologous to the TM or portion of TM.

Thus, in one aspect, a modified coronavirus spike (S) protein is provided comprising a transmembrane domain (TM) or a portion of TM and a Cytoplasmic Tail (CT) or a portion of CT, wherein the CT or portion of CT may be derived from influenza Hemagglutinin (HA) protein, and wherein the TM or portion of TM is heterologous to the CT or portion of CT. The modified coronavirus spike (S) protein is also referred to as modified S protein.

The cytoplasmic tail domain may also be referred to as "cytoplasmic tail", "cytosolic tail domain", "CT", "CTD", "cytoplasmic domain", "CP", "CPD" or "C-terminal domain" and the like. The cytoplasmic tail domain may also encompass a portion of the cytoplasmic tail domain.

It has been found that the modified viral structural proteins, such as the modified S proteins disclosed herein, have improved characteristics compared to wild-type or unmodified viral structural proteins (e.g., S proteins). Examples of improved characteristics of the modified viral structural proteins (e.g., modified S proteins) include, but are not limited to, increased yields of modified viral structural proteins when expressed in a host or host cell as compared to wild-type or unmodified viral structural proteins; the integrity, stability, or both the integrity and stability of the viral structural protein are improved when expressed in a host or host cell as compared to the wild-type or unmodified viral structural protein; the integrity, stability, or both of the integrity and stability of a virus-like particle (VLP) comprised of a modified viral structural protein is improved compared to the integrity, stability, or both of a VLP comprising a VLP that does not comprise a modified viral structural protein as described herein; the yield of VLPs comprising modified viral structural proteins is increased when expressed in a host cell as compared to the yield of VLPs not comprising modified viral structural proteins expressed in the same or substantially similar host cell.

In addition, methods of producing virus-like particles (VLPs) comprising modified viral structural proteins (e.g., modified S proteins) in a host or host cell are described. It was observed that when VLPs comprising modified viral structural proteins, such as modified S proteins, wherein native or wild-type CT HAs been replaced with CT of influenza HA as described herein, production yield of VLPs in the host is increased compared to the yield of VLPs comprising viral structural proteins i) comprising native CT or ii) comprising modified viral structural proteins wherein transmembrane domains (TM) and CT have been replaced with TM and CT of influenza HA.

The transmembrane domain may also be referred to as "TM" or "TMD". The transmembrane and cytoplasmic tail domains may be referred to as TMCT or TM/CT.

Fig. 3A shows that when modified S protein (e.g., modified SARS-CoV-2S protein) is expressed in a plant, the yield or protein accumulation (expressed as fold change) of modified S protein provides about 2-fold compared to the yield or protein accumulation of S protein with native TMCT (constructs 8586, 8589 and 8591) when native transmembrane and cytoplasmic tail (TMCT) are replaced with TMCT (constructs 8592, 8595 and 8597) from influenza HA. Furthermore, when the modified S protein (e.g., modified SARS-CoV-2S protein) is expressed in plants, where only the Cytoplasmic Tail (CT) is replaced with CT of influenza HA (constructs 8610, 8611, and 8671), protein accumulation (expressed as fold change) of the modified S protein with CT of influenza HA is further increased by between about 1.74 to 2.14 fold compared to accumulation of the modified S protein where TMCT HAs been replaced with TMCT of influenza HA. Accordingly, protein accumulation of the modified S protein of CT with influenza HA is increased between about 3.57 to 4.40 fold compared to accumulation of S protein with native transmembrane and cytoplasmic tail (wtTMCT).

FIG. 3B shows that a higher protein accumulation was observed for the modified S protein (modified SARS-CoV-2S protein) with cytoplasmic tail (H5 i CT) from influenza HA compared to protein accumulation for the S protein with wild-type TMCT (wt TMCT) or for the modified S protein with TMCT (H5 i TMCT) from influenza HA from crude plant extracts. Modified S protein with cytoplasmic tail (H5 i CT) from influenza HA was only visible by coomassie brilliant blue staining. The band of the modified S protein with cytoplasmic tail (H5 iCT) from influenza HA is more pronounced and thicker than the band of the S protein with wild-type TMCT (wt TMCT) or the modified S protein with TMCT (H5 iTMCT) of influenza HA-see band of about 150kDa labeled S protein. The thickness of the bands corresponds to the amount of protein present, indicating that the H5i CT S protein accumulates more protein. This higher protein accumulation was observed regardless of the expression enhancer used.

Similar results were obtained, as discussed further below in more detail, wherein the modified S protein included SARS-CoV-1S protein with cytoplasmic tail from influenza HA (see fig. 16A) or MERS CoV S protein with cytoplasmic tail from influenza HA (see fig. 19A).

FIG. 3C shows accumulation of S protein (SARS-CoV-2S protein) by immunoblotting analysis of crude plant extracts. Higher accumulation of modified S protein was observed when the modified S protein with cytoplasmic tail from influenza HA (H5 i CT) was expressed in plants, compared to S protein with wild-type TMCT (wt TMCT) and modified S protein in which both the transmembrane domain and cytoplasmic tail (TMCT) domain have been replaced with TMCT (H5 i TMCT) from influenza HA. The immunoblot analysis in FIG. 3C further shows that the SARS CoV-2S protein comprises both an S1 domain/subunit (upper panel, detected with anti-SARS-CoV-2S 1 antibody) and an S2 domain/subunit (lower panel, detected with anti-SARS-CoV-2S 2 antibody) and has a molecular weight of about 150 kDa.

The present specification provides modified viral structural proteins, wherein the modified viral structural proteins may be modified coronavirus spikes or surface proteins (S proteins). The modified S protein comprises, in order, an extracellular domain, a transmembrane domain (TM) or a portion of TM, and a Cytoplasmic Tail (CT) domain or a portion of CT, wherein the extracellular domain and transmembrane domain are derived from coronavirus and the CT or a portion of CT is derived from CT of influenza Hemagglutinin (HA) protein. The extracellular domain and the transmembrane domain or a portion of the TM may be derived from the same coronavirus. Thus, the extracellular domain and the transmembrane domain or a portion of the TM of the modified structural protein are homologous (i.e., non-heterologous) to each other, while CT or a portion of CT is heterologous to the extracellular domain and the transmembrane domain.

Furthermore, the transmembrane domain (TM) or a portion of TM of the modified S protein may be derived from a coronavirus that is different from the extracellular domain. Thus, the TM or a portion of the TM in the modified S protein may be heterologous (non-homologous) to both the extracellular domain of the modified S protein and the CT domain or a portion of the CT. Similarly, the extracellular domain may be heterologous (non-homologous) to the TM or a portion of TM and the CT domain or portion of CT of the modified S protein. For example, the extracellular domain of the modified S protein may be derived from a first coronavirus, TM or a portion of TM may be derived from a second coronavirus, and CT or a portion of CT may be derived from influenza HA. The first coronavirus and the second coronavirus may belong to different coronavirus families, subgroups, types, subtypes, lineages or strains. Thus, the first coronavirus and the second coronavirus may be heterologous to each other and may also be heterologous to the virus family derived from CT or a part of CT, respectively.

For example, the first coronavirus from which the S protein extracellular domain is derived may be from any coronavirus, such as, for example, an alpha coronavirus (alpha-CoV) or a beta coronavirus (beta-CoV). Non-limiting examples of first coronaviruses from which the extracellular domain of the S protein may be derived are Duvinacoviruses, such as, for example, HCoV-229E, setracoviruses, such as, for example, HCoV-NL63. A lineage Abeta coronavirus, such as, for example, HCoV-OC43 or HCoV-HKU1, a lineage Abeta coronavirus, such as, for example, SARS-CoV or SARS-CoV 2, or a lineage Abeta coronavirus, such as, for example, MERS-CoV. The second coronavirus from which the TM is derived may belong to a family, subgroup, type, subtype, lineage or strain of coronavirus that is different from the first coronavirus from which the extracellular domain is derived. For example, the second coronavirus from which the S protein TM is derived may be from any coronavirus, such as, for example, an alpha coronavirus (alpha-CoV) or a beta coronavirus (beta-CoV), so long as the second coronavirus is heterologous to the first coronavirus. Non-limiting examples of secondary coronaviruses from which the TM of S protein may be derived are Duvinacovirus, such as, for example, HCoV-229E (also known as 229E-CoV), setracovirus, such as, for example, HCoV-NL63 (NL 63-CoV), lineage Abeta coronavirus, such as, for example, HCoV-OC43 (also known as OC 43-CoV) or HCoV-HKU1 (HKU 1-CoV), lineage Abeta coronavirus, such as, for example, SARS-CoV (also known as SARS-CoV 1) or SARS-CoV 2, or lineage Abeta coronavirus, such as, for example, MERS-CoV (also known as "MERS").

The domains in the coronavirus S protein, such as the SARS-CoV-1S protein, the SARS-CoV-2S protein, the MERS CoV S protein, the OC43-CoV S protein or the 229E-CoV S protein, can be readily identified by methods known in the art. For example, domains such as transmembrane domains can be identified by determining the degree of hydrophobicity of the amino acid sequence of the protein, e.g., using a transmembrane prediction program (e.g., expert Protein Analysis System; swiss Institute of Bioinformatics running expasy. Org; or the Dense Alignment Surface Method, cserzo m., et al 1997, prot. Eng.10, vol. 6, pages 673-676; lovkema j.s.1998, FEMS Microbiol rev.22,4, stages 305-322), by determining the hydrophilicity profile of the amino acid sequence of the protein (e.g., kyte-Doolittle hydrophilicity profile), by determining the three-dimensional protein structure and identifying structures that are thermodynamically stable in the membrane (e.g., single alpha helices, stable complexes of some transmembrane alpha helices, transmembrane beta barrel, beta helices, or any other structure that is thermodynamically stable in the membrane).

Furthermore, the domains within the coronavirus S protein may be determined by comparison with known protein sequences, for example by sequence alignment. Sequence alignment methods for comparison are well known in the art and will be described further below.

The domains and domain organization of coronavirus S proteins are well known and described. All coronavirus spike proteins (S proteins) share the same organization in two subunits or domains: the N-terminal subunit (or domain) named S1, which is responsible for receptor binding, and the C-terminal S2 subunit (or domain), which is responsible for viral attachment, membrane fusion, and viral entry.

FIG. 1A shows a schematic representation of the position of the S protein and its subunits and domains and S1/S2 and S2' cleavage sites of coronaviruses. The S1 subunit is located distally to the viral membrane and comprises a Receptor Binding Domain (RBD) that mediates viral attachment to its host receptor. The S2 subunit comprises a fusion protein mechanism, e.g., a fusion peptide, two heptad repeats (HR 1 and HR 2), the central helical and transmembrane domains typical of fusion glycoproteins, and the cytoplasmic tail domain (see, e.g., kirchdoerfer et al, nature, 3/v. In 2016; 531 (7592): 118-2, supra).

The transmembrane domain (TM) and cytoplasmic tail domain (CT) are located at the C-terminal end of the S2 subunit. Although these domains are maintained in all coronaviruses (see FIG. 1A and Corver et al, virol J.2009;6:230, incorporated herein by reference), different references, teams and authors mention different amino acid numbering for these domains.

For example, amino acid (aa): 1214-1234 may be assigned to TM and aa 1235-1273 may be assigned to CT in the S protein of SARS-CoV-2 (see, e.g., uniProtKB-P0DTC2 (spike_SARS 2)). When the SARS-CoV-2 sequence (SEQ ID NO: 1) is aligned with the SARS-CoV-1 sequence of Kirchdoerfer et al (Nature 2016, 3 months; 531 (7592): 118-2), SARS-CoV-2TM corresponds to amino acids 1214-1236, and SARS-CoV-2CT corresponds to amino acids: 1237-1273.

For the purposes of the present disclosure, the TM and CT of the native (unmodified) S protein correspond to the following amino acids when aligned with the coronavirus S protein reference sequence (SEQ ID NO: 1): TM: amino acids 1214-1234 and CT: amino acid: 1235-1273.

When 15 amino acids including the Signal Peptide (SP) are removed from the S protein, TM corresponds to the reference sequence SEQ ID NO:2, and CT corresponds to amino acids 1199-1219 of SEQ ID NO:2 (see also table 1 for reference sequences and numbers).

The TM of the coronavirus S protein has a highly conserved N-terminal aromatic-rich extension followed by a hydrophobic sequence (see fig. 22 and core et al, virology Journal 6, 230 (2009)). The consensus sequence of the coronavirus S protein TM domain is: WYYXWLGFIAGLXAXXX { X } VXXL (SEQ ID NO: 132), (wherein { X } may not be present).

For example, the coronavirus S protein TM domain consensus sequence may be: WY [ I/V ] WLGFIAGL [ V/I ] A [ L/I ] [ A/V ] [ L/M ] { X } V [ F/T ] [ F/I ] XL (SEQ ID NO: 133), (wherein { X } may be C or absent).

Table 1. Non-limiting examples of the positions of TM and CT domains in the modified S protein and the corresponding amino acid positions in the reference sequence.

¹ Numbering excludes signal peptide, CT is derived from influenza HA

² Numbering includes signal peptide, CT is natural

³ Numbering excludes signal peptides, CT is native

Despite the differences in the residue numbers assigned to the TM and CT domains, one skilled in the art will be able to determine the edges or boundaries of these domains in the coronavirus S protein using, for example, known methods as described below.

In modified coronavirus S proteins, a heterologous CT or portion of CT that may be derived from influenza HA may be fused directly to the C-terminus of the TM or portion of the TM of coronavirus S protein, or a heterologous CT or portion of CT may be fused to the C-terminus of the TM or portion of the TM of coronavirus S protein having an intermediate peptide sequence (also referred to as a linker or linker sequence). Thus, the modified S protein may comprise an intermediate peptide, wherein the intermediate peptide sequence fuses CT or a portion of CT to the C-terminus of TM or a portion of TM.

A heterologous CT, a portion of a CT, or an intermediate peptide sequence with a heterologous CT may be fused to an amino acid in the C-terminal portion of the TM domain (e.g., within 4 amino acids of the C-terminal end of the TM domain defined in table 1, reference SEQ ID NO:1, 2, 21, 114, 115, 160, or 161) or the N-terminal portion of the CT domain (e.g., within 4 amino acids of the N-terminal end of the CT domain defined in table 1, reference SEQ ID NO:1, 2, 21, 114, 115, 160, or 161).

For example, the coronavirus TM may be encoded in a sequence corresponding to SEQ ID NO:1, any one of amino acid residues 1230-1238. Thus, the C-terminus of coronavirus TM may be a sequence corresponding to SEQ ID NO:1 from amino acids 1230 to 1238. In one example, coronavirus TM may be found in a nucleic acid sequence corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1230 in 1. In another example, coronavirus TM may be found in a nucleic acid sequence corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1231. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1232 in 1. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at amino acid residue of amino acid 1233. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1234 in 1. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1235 in 1. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1236 in 1. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1237 in 1. In another example, TM may be found at a position corresponding to SEQ ID NO:1, and amino acid residue 1238 in seq id no. In a preferred embodiment, the TM may be represented in a sequence corresponding to SEQ ID NO:1, and ends at the amino acid residue of amino acid 1234 in 1.

In another example, coronavirus TM or a portion of TM may be found in a nucleic acid sequence corresponding to SEQ ID NO:2 or 21, and amino acid residues of any of amino acids 1215-1219. Thus, the C-terminus of coronavirus TM or a portion of TM may be a sequence corresponding to SEQ ID NO:2 or 21, amino acids 1215-1224 of any one of amino acids 2 or 21. In one example, coronavirus TM or a portion of TM may be found in a nucleic acid sequence corresponding to SEQ ID NO:2 or 21 at amino acid residue 1215 in amino acid 2 or 21. In another example, TM or a portion of TM may be found in the sequence corresponding to SEQ ID NO:2 or 21, and ending at amino acid residue 1216 in amino acid 2 or 21. In another example, TM or a portion of TM may be found in the sequence corresponding to SEQ ID NO:2 or 21 at amino acid residue 1217 in amino acid 2 or 21. In another example, TM or a portion of TM may be found in the sequence corresponding to SEQ ID NO:2 or 21, and at amino acid residue 1218 in amino acid 2 or 21. In another example, TM or a portion of TM may be found in the sequence corresponding to SEQ ID NO:2 or 21 at amino acid residue 1219 in amino acid 2 or 21.

The intermediate peptide sequence that can fuse heterologous CT to the C-terminus of TM or a portion of TM from the coronavirus S protein can have a length of 0-10 amino acids. Thus, the intermediate peptide sequence may have a length of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids. The intermediate peptide sequence may be derived from a coronavirus protein, e.g., the intermediate peptide sequence may be derived from the C-terminus of the TM of the coronavirus S protein or the N-terminus of the CT of the coronavirus S protein, or both. The intermediate peptide sequence may also be derived from an influenza HA protein, e.g., the intermediate peptide sequence may be derived from the C-terminus of TM of the influenza HA protein or from the N-terminus of CT of the influenza HA protein, or both. Furthermore, the intermediate peptide sequence may be heterologous to the HA portion of the coronavirus and/or modified S protein, or the intermediate peptide sequence may be an artificial sequence.

Non-limiting examples of sequences of the TM/CT domain (also referred to as chimeric TMCT) of the modified S protein are shown below. The sequence of the TM domain from the coronavirus S protein is underlined and the CT domain derived from influenza HA is shown in bold. The italic and bold sequences are derived from the sequence of TM of influenza HA. The italic and underlined sequences are derived from the CT sequences of the coronavirus S protein.

SARS-CoV-2

-WYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQCRICI(SEQ ID NO:18)(wtTM/H5iCT)

-WYIWLGFIAGLIAIVMVTIM (SEQ ID NO：19)(wtTM/H5iCT V1)

-WYIWLGFIAGLIAIVMVTIM (SEQ ID NO：37)(wtTM/H5iCT V2)

-WYIWLGFIAGLIAIVMVTIMLCCMCSNGSLQCRICI(SEQ ID NO：38)(wtTM/H5iCT V3)

-WYIWLGFIAGLIAIVMVTIMLCCSNGSLQCRICI(SEQ ID NO：39)(wtTM/H5iCT V4)

-WYIWLGFIAGLIAIVMVTIMLSFWMCSNGSLQCRICI(SEQ ID NO：126)(wtTM/H1iCT)

-WYIWLGFIAGLIAIVMVTIMLMWACQKGNIRCNICI(SEQ ID NO:127)(wtTM/H3iCT)

-WYIWLGFIAGLIAIVMVTIMLGLWMCSNGSMQCRICI(SEQ ID NO:128)(wtTM/H6iCT)

-WYIWLGFIAGLIAIVMVTIMLVFICVKNGNMRCTICI(SEQ ID NO:129)(wtTM/H7iCT)

-WYIWLGFIAGLIAIVMVTIMLLFWAMSNGSCRCNICI(SEQ ID NO:130)(wtTM/H9iCT)

-WYIWLGFIAGLIAIVMVTIMLVVYMVSRDNVSCSICL(SEQ ID NO:131)(wtTM/BiCT)

SARS-CoV-1

-WYVWLGFIAGLIAIVMVTILLSLWM CSNGSLQCRICI(SEQ ID NO：118)(wtTM/H5iCT)

-WYVWLGFIAGLIAIVMVTILLCCSNGSLQCRICI(SEQ ID NO：119)(wtTM/H5iCT V4)

-WYVWLGFIAGLIAIVMVTILLSFWM CSNGSLQCRICI(SEQ ID NO：120)(wtTM/H1cCT)

MERS-CoV

-WYIWLGFIAGLVALALCVFFILSLWMCSNGSLQCRICI(SEQ ID NO：123)(wtTM/H5iCT)

-WYIWLGFIAGLVALALCVFFILCCSNGSLQCRICI(SEQ ID NO：124)(wtTM/H5iCT V4)

-WYIWLGFIAGLVALALCVFFILSFWMCSNGSLQCRICI(SEQ ID NO：125)(wtTM/H1cCT)

OC43-CoV

-WYVWLLICLAGVAMLVLLFFISLWMCSNGSLQCRICI(SEQ ID NO：164)(wtTM/H5iCT)

-WYVWLLICLAGVAMLVLLFFICCSNGSLQCRICI(SEQ ID NO：165)(wtTM/H5iCT V4)

-WYVWLLICLAGVAMLVLLFFISFWMCSNGSLQCRICI(SEQ ID NO：166)(wtTM/H1cCT)

229E-CoV

-WWVWLCISVVLIFVVSMLLLSLWMCSNGSLQCRICI(SEQ ID NO：169)(wtTM/H5iCT)

-WWVWLCISVVLIFVVSMLLLCCSNGSLQCRICI(SEQ ID NO：170)(wtTM/H5iCT V4)

-WWVWLCISVVLIFVVSMLLLSFWMCSNGSLQCRICI(SEQ ID NO：171)(wtTM/H1cCT)

The modified coronavirus S protein may comprise chimeric TMCT. For example, chimeric TMCT may include an N-terminal sequence derived from the coronavirus S protein and a C-terminal sequence derived from the influenza HA protein, as shown in table 1B. TM may include sequences as shown in the column labeled "S protein TM sequence" and CT may include sequences as shown in the column labeled "HA protein CT sequence". CT and TM may be linked by the sequences shown in the columns labeled "S protein CT sequence" and/or "HA protein TM sequence" (also referred to as an intermediate sequence or linker, as described further below).

Table 1B: non-limiting examples of TM and CT sequences in modified S proteins. Amino acid positions within the reference sequence are indicated.

For example, the N-terminal sequence derived from coronavirus S protein TM may include at least the following:

Corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, at least 19 amino acids 1-19;

corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, at least 20 amino acids 1-20;

corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, at least 21 amino acids 1-21;

corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, at least 22 amino acids 1-22;

corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, at least 23 amino acids 1-23;

corresponding to SEQ ID NO: 18. 19, 37, 38, 39, 118, 119, 123, 124, 164, 165, 169, or 170, and at least 24 amino acids 1-24.

The N-terminal sequence derived from coronavirus S protein TM may comprise a sequence corresponding to SEQ ID NO:18 or 169, or at least 20 amino acids corresponding to amino acids 1-20 of SEQ ID NO:118 or 164, or at least 21 amino acids corresponding to amino acids 1-21 of SEQ ID NO:123 at least 22 amino acids 1-22; and one or more amino acids from the C-terminus of influenza HA protein TM. The N-terminal sequence derived from coronavirus S protein TM may comprise a sequence corresponding to SEQ ID NO:18 or 169, or at least 20 amino acids corresponding to amino acids 1-20 of SEQ ID NO:118 or 164, or at least 21 amino acids corresponding to amino acids 1-21 of SEQ ID NO:123 at least 22 amino acids 1-22; and one or more amino acids from the C-terminus of influenza HA protein TM. The one or more amino acids from the C-terminus of influenza HA protein TM may comprise 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids. For example, the one or more amino acids may be 2, 3 or 4 amino acids. One or more amino acids from the C-terminal end of influenza HA protein TM may be a conservative substitution of A, C, G, L, S, M, W or A, C, G, L, S, M, W, or a combination thereof. In one example, the one or more amino acids from the C-terminus of influenza HA protein TM may be selected from a conservative substitution of AG or AG, an conservative substitution of AGL or AGL, a conservative substitution of MAGL or MAGL.

The modified coronavirus S protein may further comprise a chimeric CT comprising an N-terminal sequence derived from the coronavirus S protein CT and a C-terminal sequence derived from the influenza HA protein CT.

The N-terminal sequence derived from coronavirus S protein CT may comprise one or more amino acids. The one or more amino acids from the N-terminus of coronavirus S protein CT may comprise 0, 1, 2, 3, 4 or 5 amino acids. For example, one or more than one amino acid may be 1, 2, or 3 amino acids. One or more amino acids from the N-terminus of the coronavirus S protein CT may be a conservative substitution of C or M or C or M. In one example, the one or more amino acids from the N-terminus of the coronavirus S protein may be selected from a conservative substitution of C or C, a conservative substitution of CC or CC, or a conservative substitution of CCM or CCM.

The C-terminal sequence derived from influenza HA protein CT may comprise a sequence corresponding to SEQ ID NO:18 from amino acids 27 to 37 of 18. The N-terminal sequence derived from influenza HA protein CT may also include a sequence corresponding to SEQ ID NO:18, at least 12 amino acids 26-37 corresponding to SEQ ID NO:18, at least 13 amino acids 25-37 corresponding to SEQ ID NO:18, at least 14 amino acids of amino acids 24-37, corresponding to SEQ ID NO:18, or at least 15 amino acids corresponding to amino acids 23-37 of SEQ ID NO:18 of amino acids 22-37.

In another example, the C-terminal sequence derived from influenza HA protein CT may include at least the following:

corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131, amino acids 27-37;

corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131, amino acids 26-37;

corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131, amino acids 25-37;

corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131 amino acids 24-37;

corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131 amino acids 23-37; or alternatively

Corresponding to SEQ ID NO: 126. 127, 128, 129, 130 or 131, or at least 16 amino acids 22-37.

For example, CT may include sequences as shown in table 1B (HA protein CT sequences). For example, CT may comprise SEQ ID NO: 18. 126, 128, 129, 130, 131, 118, 120, 164 or 166, amino acids 22-37; or SEQ ID NO:19 amino acids 25-40; or SEQ ID NO:37 amino acids 24-39; or SEQ ID NO:38 from amino acids 25 to 36; or SEQ ID NO:39 or 119, amino acids 24-34; or SEQ ID NO:127 from amino acids 22 to 36; or SEQ ID NO:118 or 164 amino acids 22-37; or SEQ ID NO: amino acids 23-38 of 123 or 125; or SEQ ID NO:124 amino acids 25-35; or SEQ ID NO:165 amino acids 24-34; or SEQ ID NO:169 amino acids 21-36; or SEQ ID NO:170 amino acids 23-33; or SEQ ID NO: 21-36.

Influenza CT or a portion of CT may be fused or conjugated to TM or a portion of TM of S protein with an intermediate peptide sequence. For example, the intermediate peptide sequence may be derived from influenza CT, S protein TM, or a combination thereof, or the intermediate peptide sequence may be an artificial sequence. The intermediate peptide sequences may be of different lengths. For example, the intermediate peptide sequence may be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids long, preferably the intermediate peptide sequence is between 2 and 8 amino acids long. In one example, the intermediate peptide sequence is 2 amino acids long and may, for example, include the sequence LC. In another example, the intermediate peptide sequence is 4 amino acids long and may, for example, include the sequence LCCM. In another example, the intermediate peptide sequence may be 5 amino acids long and may, for example, include the sequence LSLWM. In another example, the intermediate peptide sequence may be 7 amino acids long and may, for example, include the sequence agllwm. In another example, the intermediate peptide sequence may be 8 amino acids long and may, for example, include the sequence maglswm.

For example, TMCT of the modified S protein may include or have 90-100% or any amount of sequence identity or sequence similarity to:

-WYIWLGFIAGLIAIVMVTIM-(X)n-CSNGSXXCXICI(SEQ ID NO：64)、

-WYVWLGFIAGLIAIVMVTIL- (X) n-CSNGSXXCXICI (SEQ ID NO: 134) or

-WYIWLGFIAGLVALALCVFFIL-(X)n-CSNGSXXCXICI(SEQ ID NO：135)、

-WYVWLLICLAGVAMLVLLFFI-(X)n-CSNGSXXCXICI(SEQ ID NO：172)、

-WWVWLCISVVLIFVVSMLLL-(X)n-CSNGSXXCXICI(SEQ ID NO：173)，

Wherein (X) _n Is an intermediate peptide sequence, wherein the intermediate peptide sequence may have a length of 0 to n amino acid residues, wherein n may be any length of 0-10, such as 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids, and wherein X may comprise any amino acid, e.g., X may be a conservative substitution of A, C, G, F, L, S, M, W or A, C, G, F, L, S, M, W, or a combination thereof.

Non-limiting intermediate peptide sequences (X) _n The following may be included:

-(X) ₀ the intermediate peptide sequence is absent;

-(X) ₁ including, for example, the sequences L or C, or conservative substitutions of L or C;

-(X) ₂ including, for example, the sequence LC, or conservative substitutions of LC;

-(X) ₃ including, for example, the sequence LCC, or conservative substitutions of LCC;

-(X) ₄ including, for example, conservative substitutions of the sequence LCCM or LCCM, conservative substitutions of SLWM or SLWM, or conservative substitutions of SFWM or SFWM;

-(X) ₅ including, for example, the sequence LSLWM or conservative substitutions of LSLWM, or conservative substitutions of LSFWM or LSFWM;

-(X) ₆ including, for example, the sequence GLSLWM, or conservative substitutions of GLSLWM;

-(X) ₇ including, for example, the sequence AGLSLWM, or conservative substitutions of AGLSLWM, or

-(X) ₈ Including, for example, the sequence MAGLSLWM, or conservative substitutions of MAGLSLWM.

FIG. 5B shows the fold change in protein accumulation of a modified S protein with a variable edge (intermediate peptide sequence) between the SARS-COV-2 Transmembrane (TM) domain and the H5A/Indonesia/5/05 HA Cytoplasmic Tail (CT) domain, wtTM/H5iCT V1 (SEQ ID NO:19, product of construct 8980), wtTM/H5iCT V2 (SEQ ID NO:37, product of construct 8981), wtTM/H5iCT V3 (SEQ ID NO:38, product of construct 8982) and wtTM/H5iCT 4 (product of construct 8983) when expressed in a plant, compared to protein accumulation of a modified S protein in which the cytoplasmic tail of the coronavirus S protein HAs been replaced with the H5A/Indonesia/5/05 HA wtTM/H5iCT (SEQ ID NO:18, product of construct 8671). All the modified S proteins tested showed protein accumulation with no statistically significant differences between the alternative form and wtTM/H5iCT reference control.

Similarly, modified S proteins comprising SARS-CoV-1S protein in wtTM/H5iCT V4 form with TMCT (FIG. 16A) or MERS S protein in wtTM/H5iCT V4 form with TMCT (FIG. 19A) showed increased protein accumulation when expressed in plants compared to protein accumulation of wild-type S protein (wtTMCT) or S protein in which TMCT HAs been replaced with TMCT of H5A/Indonesia/5/05 HA (H5 iTMCT). Furthermore, OC43 CoV S protein in wtTM/H5iCT V4 form with TMCT showed increased protein accumulation when expressed in plants compared to protein accumulation of OC43 CoV S protein with wild-type TMCT (wtTMCT) (fig. 23A).

Thus, the modified S protein may comprise TM and CT domains (TM/CT), wherein a portion of CT or CT is fused to the C-terminus of a portion of TM or TM via an intermediate peptide sequence, wherein the intermediate peptide sequence comprises the sequence X _n 。

Furthermore, the modified S protein may comprise TM and CT domains (TM/CT) comprising a sequence identical to SEQ ID NO: 18. 19, 37, 38, 39, 64, 126, 127, 128, 129, 130, 131, 118, 119, 120, 123, 124, 125, 134, 135, 164, 165, 166, 169, 170, 171, 172, or 173, has a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

The modified S protein may comprise CT or a portion of CT comprising a sequence identical to SEQ ID NO:18, amino acids 22-37 of SEQ ID NO:19, amino acids 21-40 of SEQ ID NO:37, amino acids 21-39 of SEQ ID NO:38 or amino acids 25-36 of SEQ ID NO:39, amino acids 24-34, SEQ ID NO:126, amino acids 22-37, SEQ ID NO:127, amino acids 22-36, SEQ ID NO:128, amino acids 22-37 of SEQ ID NO:129, amino acids 22-37, SEQ ID NO:130 or amino acids 22-37 of SEQ ID NO:131 has a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

The modified S protein may comprise a TM or a portion of a TM, which comprises a sequence identical to SEQ ID NO:18, amino acids 1-20, SEQ ID NO:19, amino acids 1-20, SEQ ID NO:37, amino acids 1-20 of SEQ ID NO:38, amino acids 1-24, SEQ ID NO:39, amino acids 1-23, SEQ ID NO:118, amino acids 1-21, SEQ ID NO:119, amino acids 1-23, SEQ ID NO:123, amino acids 1-22, SEQ ID NO:124, amino acids 1-24, SEQ ID NO:164, amino acids 1-21, SEQ ID NO:165, amino acids 1-23, SEQ ID NO:169 or amino acids 1-20 of SEQ ID NO:170 has a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween. Furthermore, a modified S protein as described herein may comprise TM or a portion of TM comprising a sequence that is identical to SEQ ID NO:132 or 133 has from 80% to 100% identity.

Furthermore, the modified S protein may comprise a sequence identical to SEQ ID NO: 5. 59, 60, 61, 62, 95, 96, 97, 108, 109 or 110, has 70% to 100% sequence identity or sequence similarity, e.g., the modified S protein may comprise a sequence identical to SEQ ID NO: 5. 59, 60, 61, 62, 95, 96, 97, 108, 109, or 110 has a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

Viral structural proteins, such as, for example, the cytoplasmic tail domain (CT) or a portion of CT of the coronavirus S protein, may be replaced with CT or a portion of CT from influenza Hemagglutinin (HA), as described below, and the resulting protein is referred to as a modified viral structural protein. Thus, a coronavirus S protein in which the native CT or a portion of the native CT HAs been replaced with CT or a portion of CT from HA may be referred to as a modified coronavirus S protein or modified S protein. As described above, HA CT or a portion of HA CT may be fused directly to the N-terminus of the coronavirus TM domain, or may be fused via an intervening peptide sequence to the N-terminus of coronavirus TM or a portion of the TM. Thus, HA CT or a portion of HA CT may be fused to the C-terminus of S protein TM or a portion of S protein TM via an intermediate peptide sequence.

Influenza "hemagglutinin" or "HA" is a homotrimeric membrane type I glycoprotein, typically comprising a signal peptide, an HA1 domain, and an HA2 domain, which includes a transmembrane anchor site at the C-terminus and a small cytoplasmic tail (see, e.g., fig. 1C and 2). The amino acid sequences of HA from various influenza strains are well known in the art. Furthermore, the amino acid sequences and nucleotide sequences encoding HA are well known and available, for example, see BioDefence Public Health base (influenza; see URL: biohealthbase. Org) or national center for biotechnology information (see URL: ncbi. Nlm. Nih. Gov), both of which are incorporated herein by reference. Exemplary amino acid sequences of the cytoplasmic tail domains of HA from different influenza strains are shown in figure 2.

Although different references and study groups assigned different lengths for the CT of HA, the N-terminal sequence of CT HAs been shown to be conserved among HA from different influenza subtypes and strains, and at least 5 residues have sequence identity for at least 10 of the 13 HA subtypes (Simpson and Lamb 1992,Journal of Virology,790-803). FIG. 2 shows an alignment of amino acid sequences from exemplary influenza strains with conserved sequences in the N-terminal portion of HA proteins. The consensus sequence of the influenza Cytoplasmic Tail (CT) domain is: XXWMCSNGSXXCXICI (SEQ ID NO: 15) (see also FIG. 2, C-terminal end of SEQ ID NO: 14)

The CT sequence corresponding to the HA cytoplasmic tail domain consensus sequence may be fused to the C-terminus of the TM of the coronavirus S protein directly or via an intermediate peptide sequence (linker sequence) as discussed above.

Furthermore, amino acid residues located at the N-or C-terminus of the native influenza HA TM/CT border may also be included in the CT sequence, fused to the TM or part of the TM of the modified coronavirus S protein, either directly or via an intermediate peptide sequence.

Thus, the sequence of CT or a portion of CT may, for example, start with a sequence corresponding to SEQ ID NO:14 from amino acid 30 to 40. Thus, the N-terminus of the CT sequence may be a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or any one of amino acids 30-40. In one example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, amino acid residue of amino acid 30. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid residue 31. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or an amino acid residue of amino acid 32. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid 33. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid residue 34. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid residue of amino acid 35. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: amino acid residues 6-13 or 14, amino acid 36. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid residue of amino acid 37. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: amino acid residues 6-13 or 14 of amino acid 38. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid 39. In another example, the CT sequence may start with a sequence corresponding to SEQ ID NO: 6. 7, 8, 9, 10, 11, 12, 13 or 14, or amino acid residue 40.

The Cytoplasmic Tail (CT) or a portion of CT of the modified S protein may be derived from CT or a portion of CT of Hemagglutinin (HA) of any influenza type, subtype, or strain. For example, CT may be derived from HA of influenza a or influenza b. For example, CT may be derived from HA of influenza subtypes H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, or H16. CT may be, for example, HA derived from subtypes H1, H2, H3, H5, H6, H7 or H9. In addition, CT or a portion of CT may be derived from HA of influenza b. Influenza B can be derived from the B/Yamagata or B/Victoria lineages.

For example, CT or a portion of CT of the modified S protein may be derived from CT of Hemagglutinin (HA) influenza H1, H3, H5, H6, H7, H9 or B strain. Non-limiting examples of influenza strains from which HA CT can be derived are influenza H1 California/7/2009, H2A/Singapore/1/1957, H3A/Minnesota/41/2019, H5A/Indonesia/5/05, H6A/Teal/Hong Kong/W312/97, H7A/Guangdong/17 SF003/2016, H9A/Hong Kong/1073/99 or B/Washington/02/2019. A non-limiting example of the amino acid sequence of HA CT is shown in FIG. 2.

As shown in FIG. 4A, when the natural Cytoplasmic Tail (CT) of the SARS-CoV-2S protein was replaced by SARS-CoV-2S with CT from influenza HA H1 California/7/2009 (H1 Calif.), H3A/Minnesota/41/2019 (H3 Minn), H6A/Teal/Hong Kong/W312/97 (H6 HK), H7A/Guangdong/17 SF003/2016 (H7 Guan), H9A/Hong Kong/1073/99 (H9 HK) or B/Washington/02/2019 (B Wash), similar fold changes in protein accumulation were observed for these modified SARS-CoV-2S proteins as compared to SARS-CoV-2S with CT from H5A/Indoneia/5/05 (H5 Ind). Immunoblot analysis confirmed these observations (see fig. 4B and 4C).

Similar results were obtained when the natural Cytoplasmic Tail (CT) of SARS-CoV-1S protein, the natural CT of MERS S protein, or the natural CT of OC43 CoV S protein was replaced with CT from influenza HA H1 California/7/2009 (H1 cCT) (see fig. 16A, 19A and 23A).

Thus, the cytoplasmic tail domain (CT) or a portion of CT can hybridize to a polypeptide having the amino acid sequence of SEQ ID NO:15, or a sequence having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 30-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 31-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, amino acids 32-50, or having the amino acid sequence of SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 33-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 34-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 35-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 36-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 37-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 38-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 39-50 having SEQ ID NO: 6. 7, 8, 9, 10, 12, 13, 14, or amino acids 40-50 having SEQ ID NO:11, or amino acids 31-49 having SEQ ID NO:11, or amino acids 32-49 having SEQ ID NO:11, or amino acids 33-49 having SEQ ID NO:11, or amino acids 34-49 having SEQ ID NO:11, or amino acids 35-49 having SEQ ID NO:11, or amino acids 36-49 having SEQ ID NO:11, or amino acids 37-49 having SEQ ID NO:11, or amino acids 38-49 having SEQ ID NO:11, or amino acids 39-49 having SEQ ID NO:3, or amino acids 548-568 having SEQ ID NO:3, or amino acids 549-568 having SEQ ID NO:3, or amino acids 550-568 having SEQ ID NO:3 or amino acids 551-568 of SEQ ID NO:3, or amino acids 552-568 having SEQ ID NO:3, or amino acids 553-568 having SEQ ID NO:3, or amino acids 554-568 having SEQ ID NO:3, or amino acids 555-568 having SEQ ID NO:3 or amino acids 556-568 having SEQ ID NO:3, or amino acids 557-568 having SEQ ID NO:3, amino acids 558-568 have about 70, 75, 80, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount sequence identity or sequence similarity therebetween.

Furthermore, the modified S protein may comprise a sequence having the amino acid sequence of SEQ ID NO: 5. 53, 54, 55, 56, 57 or 58 has 70% to 100% sequence identity or sequence similarity, e.g., the modified S protein may comprise a sequence identical to a sequence having SEQ ID NO: 5. 53, 54, 55, 56, 57 or 58 or a sequence having the sequence of SEQ ID NO:53, amino acids 25-1259, SEQ ID NO:54, amino acids 25-1259, SEQ ID NO:55, amino acids 25-1259, SEQ ID NO:56, amino acids 25-1259, SEQ ID NO:57 or amino acids 25-1259 of SEQ ID NO:58, amino acids 25-1259 have a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

In other embodiments, the modified S protein extracellular domain and/or transmembrane domain may be obtained from a coronavirus S protein other than a SARS-CoV-2S protein, e.g., from a SARS-CoV-1S protein, a MERS-CoV S protein, an OC43-CoV S protein, a 229E-CoV S protein, or the like.

As shown in fig. 16A, when compared to protein accumulation of S protein with wild-type TMCT (wt TMCT) or modified S protein with TMCT (H5 i TMCT) of influenza H5 HA from crude plant extract, higher protein accumulation was observed for the modified SARS-CoV-1S protein with the following: CT from influenza H5 HA (H5 iCT), CT from influenza H1 HA (H1 cCT) or CT from influenza H5 HA, which HAs a variable edge between SARS-CoV-1TM and H5 HA CT ("H5 iCT (V4)"). The modified S proteins assembled into high molecular weight structures (see fig. 16B-16D), which proved to be VLPs (see fig. 17A-17C). Although the protein accumulation amount of the SARS-CoV-1 protein having native TMCT is lower than the detection limit of the immunoblotting analysis, when the SARS-CoV-1S protein having modified TMCT and/or CT is present on the same gel (see FIG. 16A), the signal can be detected by the immunoblotting analysis when only the SARS-CoV-1 protein having native TMCT is present on the gel (see FIG. 16B) and VLP is observed by electron microscopy (see FIG. 17B).

Similar results were obtained for the modified MERS-CoV S protein (see fig. 19A). Higher protein accumulation (see protein band at about 175 kDa) was observed for modified MERS-CoV S proteins with CT (H5 iCT) from influenza H5HA, CT (H1 cCT) from influenza H1 HA, or CT (with variable edge between MERS-CoV TM and H5HA CT) from influenza H5HA when compared to protein accumulation of modified S proteins with wild-type TMCT (wt TMCT) or TMCT (H5 i TMCT) with influenza H5 HA. The highest accumulation was observed for the modified MERS-CoV with influenza H1 HA CT (H1 cCT). The smaller band observed at about 100kDa is likely to be a proteolytically cleaved fragment of the S protein. Without wishing to be bound by theory, it is believed that influenza HA CT substitution of native CT stabilizes MERS S protein and reduces cleavage of S protein.

As further shown in fig. 23A, low protein yields were observed in plants expressing OC43 CoV S protein with the native OC43 CoV S protein TMCT. However, when the native OC43 CoV S protein TMCT is replaced with TMCT from influenza H5HA (H5 iTMCT), CT from influenza H5HA (H5 iCT), CT from influenza H1 HA (H1 cCT) or CT from influenza H5HA (with a variable edge between OC43-CoV TM and H5HA CT) (H5 iCT (V4)), a higher protein accumulation is observed compared to the OC43 CoV S protein with native TMCT (see band at about 150 kDa. The larger band shown in the gel is considered to be a protein trimer). Similar results were observed for the modified 229E-CoV S protein (data not shown).

Furthermore, the MERS-CoV S protein, OC43-CoV S protein and 229E-CoV S protein with TMCT (H5 iTMCT) from influenza H5 HA, CT (H5 iCT) from influenza H5 HA or CT from influenza H1 HA were observed to form VLPs as shown in FIGS. 19B-19F, FIGS. 23B-23E and FIGS. 25A-25E.

Accordingly, the present disclosure provides a "modified viral structural protein", "viral structural fusion protein" or "chimeric viral structural protein", wherein the extracellular domain and transmembrane domain (TM) or a portion of TM of the viral structural protein is derived from coronavirus and the Cytoplasmic Tail (CT) or a portion of CT is derived from influenza protein. For example, the extracellular and transmembrane domains may be derived from coronavirus spike (S) proteins, while the Cytoplasmic Tail (CT) or a portion of CT may be derived from influenza HA proteins. The modified S protein may in turn comprise i) an extracellular domain derived from a coronavirus S protein (including FP, HR1 and HR2 domains of the S1 and S2 subunits), ii) a coronavirus transmembrane domain (TM) or a portion of a coronavirus TM, and iii) an influenza HA cytoplasmic tail domain (CT) or a portion of HA CT. Thus, in modified S proteins CT or a portion of CT is heterologous to the TM of the extracellular domain. Similarly, the TM (and extracellular domain) of the modified S protein is heterologous to CT. The ectodomain and transmembrane domain (TM) may be derived from the same coronavirus (i.e., the ectodomain and TM may be homologous to each other) or the ectodomain may be derived from a first coronavirus and the TM may be derived from a second coronavirus (i.e., the ectodomain and TM are heterologous to each other).

"chimeric protein" or "chimeric polypeptide" also referred to as a "fusion protein" refers to a protein or polypeptide comprising amino acid sequences from two or more sources, such as, but not limited to, extracellular and transmembrane domains derived from a first viral structural protein (e.g., derived from the coronavirus S protein) and Cytoplasmic Tails (CTs) derived from a second viral structural protein, e.g., CTs from influenza HA, fused to a single polypeptide.

The modified coronavirus S protein may include a transmembrane and cytoplasmic tail domain (TMCT), wherein TMCT is chimeric TMCT. Chimeric TMCT may include a transmembrane domain (TM), wherein TM or a portion of TM is derived from coronavirus S protein and Cytoplasmic Tail (CT), wherein CT or a portion of CT is derived from influenza Hemagglutinin (HA) protein. Furthermore, the chimeric TMCT may include native coronavirus S protein TM, chimeric coronavirus S protein/influenza HA TM, native influenza HA CT, chimeric influenza HA/coronavirus S protein CT, or a combination thereof. For example, the modified coronavirus S protein may include chimeric TMCT having native influenza HA CT and chimeric TM, wherein the chimeric TM comprises an N-terminal sequence of TM derived from the coronavirus S protein and a C-terminal sequence of TM derived from the influenza HA protein. In another example, the modified coronavirus S protein may comprise a chimeric TMCT having a native coronavirus S protein TM and a chimeric CT, wherein the chimeric CT comprises an N-terminal sequence derived from the coronavirus S protein and a C-terminal sequence derived from the influenza HA protein. In other examples, the modified coronavirus S protein may include chimeric TMCT with chimeric TM, wherein the chimeric TM includes an N-terminal sequence of TM derived from coronavirus S protein and a C-terminal sequence of TM derived from influenza HA protein, and chimeric CT, wherein the chimeric CT includes an N-terminal sequence derived from coronavirus S protein and a C-terminal sequence derived from influenza HA protein.

When reference is made in the present disclosure to a modified S protein or modified coronavirus spike (S) -protein, it refers to a modified coronavirus spike (S) -protein comprising a transmembrane domain (TM) or a portion of the S protein TM and a Cytoplasmic Tail (CT) or a portion of CT, wherein CT is derived from influenza Hemagglutinin (HA) protein, and wherein TM and CT are heterologous.

The modified S protein may comprise a sequence identical to SEQ ID NO: 5. 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 144, 145, 146, 155, 156, or 157, for example, the modified S protein may comprise a sequence identity or sequence similarity of about 70% to 100% to the sequence of SEQ ID NO: 5. 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 144, 145, 146, 155, 156 or 157 or a sequence identical to SEQ ID NO:47, amino acids 25-1259, SEQ ID NO:48, amino acids 25-1259, SEQ ID NO:49, amino acids 25-1259, SEQ ID NO:50, amino acids 25-1259, SEQ ID NO:51, amino acids 25-1259, SEQ ID NO:52, amino acids 25-1259, SEQ ID NO:53, amino acids 25-1259, SEQ ID NO:54, amino acids 25-1259, SEQ ID NO:55, amino acids 25-1259, SEQ ID NO:56, amino acids 25-1259, SEQ ID NO:57, amino acids 25-1259, SEQ ID NO:58, amino acids 25-1259, SEQ ID NO:59, amino acids 25-1262, SEQ ID NO:60, amino acids 25-1261, SEQ ID NO:61, amino acids 25-1258, SEQ ID NO:62, amino acids 25-1256, SEQ ID NO:95, amino acids 25-1243, SEQ ID NO:96, amino acids 25-1240, SEQ ID NO:97, amino acids 25-1243, SEQ ID NO:108, amino acids 25-1341, SEQ ID NO:109, amino acids 25-1338, SEQ ID NO:110, amino acids 25-1341, SEQ ID NO:144, amino acids 25-1351, SEQ ID NO:145, amino acids 25-1348, SEQ ID NO:146, amino acids 25-1351, SEQ ID NO:155, amino acids 25-1159, SEQ ID NO:156 or amino acids 25-1156 of SEQ ID NO:157 from amino acids 25 to 1159 have a sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% or any amount of sequence identity or sequence similarity therebetween.

The modified S protein may also be produced or synthesized as a modified S protein precursor (also referred to as a precursor S protein), wherein the S protein precursor comprises a modified S protein and a signal peptide, wherein the signal peptide is native to the coronavirus (i.e., homologous to the extracellular domain) or the signal peptide may be non-native or heterologous to the extracellular domain. In a non-limiting example, the native signal peptide may be replaced with a signal peptide from a protein disulfide isomerase (protein disulfide isomerase; PDI).

The modified S protein precursor may include a signal peptide that is non-native or heterologous to the extracellular domain. The non-native signal peptide may replace the entire native signal peptide or may replace a portion of the native signal peptide of the coronavirus S protein. Furthermore, the non-native or heterologous signal peptide may be fused directly to the N-terminus of the modified S protein, or the non-native or heterologous signal peptide may be fused to the N-terminus of the modified S protein via an intermediate peptide sequence.

The signal peptide (also known as a signal sequence, targeting signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide present at the N-terminus of most newly synthesized proteins, which is directed to the secretory pathway. The signal peptide is responsible for targeting proteins to the endomembrane system, including the endoplasmic reticulum and golgi apparatus, where it is co-translated by signal peptidase enzymes located in the lumen of the Endoplasmic Reticulum (ER) and produces the mature protein. Since the experimental methods for identifying targeting sequences are time consuming and laborious, different computational methods for predicting targeting signals have been developed and are well known in the art. Signal peptides generally have low sequence similarity but share some characteristic features. In order to predict Signal sequences and their cleavage sites, various prediction Methods have been developed that take these characteristic features into account, such as, for example, signalP (Bendtsen et al, J Mol biol.200 Jul 16;340 (4): 783-95; petersen et al, nature Methods8, pp 785-786 (2011)), signal-CF (Chou and Shen, biochem Biophys Res Commun.2007, 8, 6 th day; 357 (3): 633-40) and Signal-BLAST (Frank and Sippl, bioinformation, 2008Oct 1;24 (19): 2172-6), which are incorporated herein by reference.

Using the SignalP prediction program, the sequence corresponding to SEQ ID NO:1, and a signal peptide cleavage site of SARS-CoV-2S protein is predicted between positions 15 and 16 of the sequence. However, the signal peptide cleavage site of the SARS-CoV-2S protein can be predicted or present at a position corresponding to the sequence of SEQ ID NO:1 between other consecutive positions of the sequence of sequences 1. For example, the signal peptide cleavage site of the SARS-CoV-2S protein is also predicted or may occur at a position corresponding to SEQ ID NO:1 between positions 13 and 14 of the sequence of 1.

The N-terminal region of the native SARS-CoV-2S protein (including the native signal peptide sequence) is as follows:

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNS(SEQ ID NO：63)

the predicted signal peptide Sequence (SP) is underlined. The sequence of grey shades corresponds to the sequence shown in table 2. The first amino acid residue of the mature SARS-CoV-2S protein can be valine (V), designated by position 1 (+1), which corresponds to V16 of the precursor S protein (the natural SARS-CoV-2S protein with the natural signal peptide). The first amino acid residue of the mature SARS-CoV-2S protein can be found in SEQ ID NO:1 or SEQ ID NO:63, as shown in table 2. For example, the first amino acid residue of the mature SARS-CoV-2S protein can be glutamine (Q), whose position is designated 14 (-2).

Table 2: SARS-CoV-2S protein sequence portion around the cleavage site of the Signal Peptide (SP). Residue numbering comes from the N-terminus containing the native signal peptide (# with SP), or from the predicted cleavage site at position V1 (# without SP), which corresponds to V16 (precursor S protein) in the sequence containing the signal peptide.

* Mature protein

Signal peptides or peptide sequences for directing the localization of expressed proteins or polypeptides to the apoplast include, but are not limited to, native (in the case of proteins) signal or leader sequences, or heterologous signal sequences such as, but not limited to, rice amylase signal peptide (mccomick 1999,Proc Natl Acad Sci USA 96:703-708) or Protein Disulfide Isomerase (PDI) signal peptides. Thus, as described herein, the modified S protein may be produced as a precursor protein comprising the modified S protein and a heterologous amino acid signal peptide sequence. For example, the modified S protein precursor may include a signal peptide from a protein disulfide isomerase (PDI SP; nucleotides 32-103 of accession number Z11499).

Accordingly, the present disclosure also provides proteins comprising modified S proteins and precursors of modified S proteins of natural or unnatural signal peptides, as well as nucleic acids encoding the proteins.

The modified viral structural protein may be a modified S protein, wherein the modified S protein is a monomeric or single chain modified S protein. The monomeric or single chain modified S protein may comprise an S1 domain (subunit) and an S2 domain (subunit), wherein the S2 domain (subunit) HAs been modified to replace the native CT of the S protein with the CT of the influenza HA protein, and wherein the modified S protein is a single continuous polypeptide chain. Monomeric or single chain modified S proteins can be trimerized to form trimers, referred to as trimer modified S proteins. Trimer is a macromolecular complex formed from three proteins that are usually non-covalently bound.

The S protein is cleaved into 2 polypeptide chains, the S1 subunit and the S2 subunit, at conserved activation cleavage sites, which remain bound as S1/S2 protomers in homotrimers. Without wishing to be bound by theory, cleavage of the S protein Cheng Yaji may be important for viral infectivity, but may not be necessary for protein trimerization.

The modified S protein may also include one or more substitutions, substitutions or mutations. For example, the modified S protein may include one or more substitutions, or mutations in the extracellular domain to increase expression, yield, stability, or to increase the expression, yield, and stability of the modified S protein in a suitable expression system.

For example, the modified S protein may include substitutions or mutations to the S1/S2 and/or S2' protease cleavage sites to prevent protease cleavage at these sites. Thus, when produced in a host or host cell, the modified S protein is not cleaved into separate S1 and S2 subunits or polypeptide chains.

Modified viral structural proteins, such as modified S proteins, may also be assembled into trimers of the modified viral structural proteins. Thus, coronavirus protein trimers comprising a modified S protein as described herein are also provided. The trimer may comprise a single chain modified S protein, wherein the single chain modified S protein comprises an S1 subunit and an S2 subunit, wherein CT of the S2 subunit HAs been replaced with CT of influenza Hemagglutinin (HA).

Trimers may also be stable in the pre-fusion conformation. Modified viral structural proteins, such as modified S proteins, may thus also include one or more substitutions, substitutions or mutations to inhibit conformational changes in the S protein from the pre-fusion conformation to the post-fusion conformation, and thereby stabilize the S protein or S protein trimer in the pre-fusion conformation.

"amino acid substitution" or "substitution" refers to the replacement of an amino acid in the amino acid sequence of a protein with a different amino acid. The terms amino acid, amino acid residue or residues are used interchangeably in the present disclosure. One or more amino acids may be substituted or replaced with one or more amino acids other than the original or wild-type amino acid at that position without changing the overall length of the amino acid sequence of the protein.

For example, modified viral structural proteins, such as modified S proteins, may be stabilized by proline substitutions, substitutions that allow disulfide bond and salt bridge formation, and/or cavity filling substitutions.

Hsieh et al (Science 2020,369 pages 1501-1505, which is incorporated herein by reference) designed and expressed a variety of SARS-CoV-2 spike protein variants in mammalian cells. An S protein variant with six proline substitutions, called HexaPro, expressed 9.8-fold higher than the S protein compared to the variant with only biproline substitutions, increased Tm by about 5 ℃ and maintained the pre-trimeric fusion conformation in mammalian cell lines. Hsieh et al considered the HexaPro variant to be the best variant.

In the present disclosure, for a polypeptide corresponding to SEQ ID NO: the highest yields were observed for the combination of four proline substitutions at positions 802, 927, 971 and 972 ("4P") of 2 and the additional single amino acid substitution at position 923. In addition, higher yields were also observed for the combination of six proline substitutions corresponding to positions 802, 877, 884, 927, 971 and 972 ("6P") and the additional single amino acid substitution at position 923.

As provided herein, a modified S protein may also include one or more substitutions, or mutations to increase stability, yield, or stability and yield of the modified protein in a host or host cell, such as, for example, in a plant or plant cell.

A modified S protein as described herein may include one or more mutations, modifications or substitutions in its amino acid sequence at any one or more amino acids corresponding to amino acids in a reference sequence as described below.

"corresponding amino acid", "corresponding to an amino acid" or "corresponding to a sequence" and the like refer to an amino acid (or nucleotide) that corresponds to an amino acid (or nucleotide) in a sequence alignment with a reference coronavirus sequence, as described below. The corresponding amino acid positions in the coronavirus sequence can be determined by alignment with the known sequence of the coronavirus S protein. Methods for alignment of sequences for comparison are well known in the art and are described further below. Examples of the corresponding amino acids are shown in table 3.

Table 3: the position of the corresponding amino acid/residue position in the coronavirus S protein. (reference sequences are shown).

1 number exclusion Signal Peptide (SP)

2 number includes a Signal Peptide (SP)

For example, the modified S protein may have one or more (e.g., two consecutive) proline substitutions at or near the boundary between the HRl domain and the central helical domain that stabilize the S ectodomain trimer in the pre-fusion conformation, as described, for example, in WO 2018/081318, which is incorporated herein by reference. Furthermore, one or more substitutions may limit and/or may prevent processing or cleavage at the cleavage site between the S1 and S2 subunits.

The modified S protein may include one or more substitutions at positions as shown in table 3. For example, the modified S protein may be found in a polypeptide corresponding to SEQ ID NO:2 (SARS-CoV-2) comprises one or more substitutions at positions 667, 668, 670, 802, 877, 884, 923, 927, 971, 972, or combinations thereof. The corresponding positions in the S proteins of SARS-CoV-1, MERS-CoV, OC43-CoV and 229E-CoV are shown in Table 3. The corresponding amino acid positions in the S proteins from other coronaviruses can be determined by methods known in the art.

GSAS-2P (971 and 972)

For example, the modified S protein may have one or more substitutions at one or more amino acids corresponding to SEQ ID NO:2, amino acid at position 667, 668, 670, 971 or 972 of the amino acid sequence.

In one aspect, the modified S protein may include substitutions, modifications or mutations corresponding to positions 667, 668, 670 or combinations thereof (numbered according to SEQ ID NO: 2). For example, the amino acid corresponding to position 667 can be substituted with glycine (G) or a conservative substitution of glycine (G), the amino acid corresponding to position 668 can be substituted with serine (S) or a conservative substitution of serine (S), and the amino acid corresponding to position 670 can be substituted with serine (S) or a conservative substitution of serine (S).

The modified S protein may also include substitutions, modifications or mutations corresponding to positions 971, 972 or at positions 971 and 972 (numbered according to SEQ ID NO: 2). For example, the amino acid corresponding to position 971 and/or 972 may be a substitution of proline (P) or a conservative substitution of proline (P).

The modified S protein may comprise one or more substitutions, wherein the one or more substitutions comprise a sequence corresponding to SEQ ID NO:2, or consists of one or more amino acid substitutions of amino acids at positions 667, 668, 670, 971, 972. Modified S proteins with one or more substitutions may be stable in the pre-fusion conformation. In addition, the modified S protein may form a trimer that is stable in the pre-fusion conformation.

For example, the modified S protein may include the following substitutions (numbered according to SEQ ID NO: 2): R667G, R668S, R670S (referred to herein as "GSAS"). The modified S protein may also have the following substitutions (numbered according to SEQ ID NO: 2): K971P and V972P (referred to herein as "2P"). Furthermore, the modified S protein may have the following substitutions (numbered according to SEQ ID NO: 2): R667G, R668S, R670S, K971P and V972P (referred to herein as "GSAS-2P").

For example, the modified S protein may have a sequence identical to SEQ ID NO:47 or an amino acid sequence identical to SEQ ID NO:47, wherein the amino acid sequence has an amino acid sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, wherein the amino acid sequence has a glycine (G) or a conservative substitution of glycine (G) at position 667, a serine (S) or a serine (S) at position 668, a serine (S) or a conservative substitution of serine (S) at position 670, a proline (P) or a conservative substitution of proline (P) at positions 971 and 972, wherein the modified S protein forms VLP upon expression.

In another example, the modified S protein may have one or more substitutions at one or more amino acids corresponding to SEQ ID NO:114 or an amino acid at position 654, 955 or 956 of the amino acid sequence corresponding to SEQ ID NO:115, amino acids at positions 730, 733, 1043 or 1044 of the amino acid sequence.

For example, the modified S protein may include the following substitutions: R654A (numbering according to SEQ ID NO: 114) or R730A and/or R733G (numbering according to SEQ ID NO: 115). The modified S protein may also have the following substitutions: K955P and/or V956P (numbering according to SEQ ID NO: 114) or V1043P and/or L1044P (numbering according to SEQ ID NO: 115). Furthermore, the modified S protein may have the following substitutions: R654A, K955P and V956P (numbered according to SEQ ID NO: 114) or R730A, R733, G, V, 1043, P, L, 1044P (numbered according to SEQ ID NO: 115).

GSAS-4P (802, 927, 971 and 972)

The modified S protein may also have substitutions at amino acids corresponding to amino acids at positions 667, 668 and 670, and further have one or more substitutions at one or more residues corresponding to positions 802, 927, 971 and 972 (numbered according to SEQ ID NO: 2). For example, the amino acids corresponding to positions 802, 927, 971 and 972 may be replaced by proline (P) or a conservative substitution of proline (P).

As shown in fig. 11A, a modified S protein with a "GSAS" modification and the following modifications: F802P, A927P, K971P, V972P (referred to as "GSAS-4P", expressed by construct 8953) showed a 2.47 fold increase in the yield of modified S protein compared to the yield of "GSAS-2P" S protein (expressed from construct 8671).

Thus, the modified S protein may comprise one or more substitutions, wherein the one or more substitutions comprise a sequence corresponding to the sequence set forth in SEQ ID NO:2, and one or more substitutions of or consisting of amino acids at positions 667, 668, 670, 802, 927, 971 and 972.

For example, the modified S protein may have a sequence identical to SEQ ID NO:48 or amino acid sequence corresponding to SEQ ID NO:48, wherein the amino acid sequence has an amino acid sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, wherein the amino acid sequence has a glycine (G) or a conservative substitution of glycine (G) at position 667, a serine (S) or a serine (S) at position 668, a serine (S) or a conservative substitution of serine (S) at position 670, a proline (P) or a conservative substitution of proline (P) at positions 802, 927, 971 and 972, wherein the modified S protein forms VLPs upon expression.

In another example, the modified S protein may have one or more substitutions at one or more amino acids corresponding to the amino acid sequence set forth in SEQ ID NO:14 or an amino acid corresponding to position 654, 786, 911, 955 or 956 of the amino acid sequence of SEQ ID NO:115, amino acid at position 730, 733, 872, 999, 1043 or 1044 of the amino acid sequence.

For example, the modified S protein may include the following substitutions: R654A (numbering according to SEQ ID NO: 114) or R730A and/or R733G (numbering according to SEQ ID NO: 115). The modified S protein may also have the following substitutions: F786P, S911P, K955P and/or V956P (numbering according to SEQ ID NO: 114) or A872P, N999P, V1043P and/or L1044P (numbering according to SEQ ID NO: 115). Furthermore, the modified S protein may have the following substitutions: R654A, F786P, S911P, K955P and V956P (numbered according to SEQ ID NO: 114) or R730A, R733G, A872, P, N999P, V1043P, L1044P (numbered according to SEQ ID NO: 115). GSAS-6P (802, 877, 884, 927, 971 and 972)

The modified S protein may also have substitutions at amino acids corresponding to amino acids at positions 667, 668 and 670, and further have one or more substitutions at one or more residues corresponding to positions 802, 877, 884, 927, 971 and 972 (numbered according to SEQ ID NO: 2). For example, the amino acids corresponding to positions 802, 877, 884, 927, 971 and 972 may be replaced by proline (P) or a conservative substitution of proline (P) (numbered according to SEQ ID NO: 2).

As shown in fig. 11A, a modified S protein with a "GSAS" modification and the following modifications: F802P, A877P, A884P, A927P, K971P, V972P (referred to as "GSAS-6P", expressed from construct 8940) showed a 2.11 fold increase in S protein yield compared to that of "GSAS-2P" S protein (expressed from construct 8671).

Thus, the modified S protein may comprise one or more substitutions, wherein the one or more substitutions comprise a sequence corresponding to SEQ ID NO:2, and one or more substitutions of or consisting of amino acids at positions 667, 668, 670, 802, 877, 884, 927, 971, and 972.

For example, the modified S protein may have a sequence identical to SEQ ID NO:49 or amino acid sequence identical to SEQ ID NO:48 having an amino acid sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, wherein the amino acid sequence has glycine (G) or a conservative substitution of glycine (G) at position 667, serine (S) or a conservative substitution of serine (S) at position 668, serine (S) or a conservative substitution of serine (S) at position 670, proline (P) or a conservative substitution of proline (P) at positions 802, 877, 884, 927, 971 and 972, wherein the modified S protein forms VLP upon expression.

In another example, the modified S protein may have one or more substitutions at one or more amino acids corresponding to the amino acid sequence set forth in SEQ ID NO:114 at position 654, 786, 861, 868, 911, 955 or 956 of the amino acid sequence of SEQ ID NO:115, amino acids at positions 730, 733, 872, 949, 956, 999, 1043 or 1044 of the amino acid sequence.

For example, the modified S protein may include the following substitutions: R654A (numbering according to SEQ ID NO: 114) or R730A and/or R733G (numbering according to SEQ ID NO: 115). The modified S protein may also have the following substitutions: F786P, A861, P, A868P, S911P, K955P and/or V956P (numbered according to SEQ ID NO: 114) or A872P, S949P, A956P, N999P, V1043P and/or V1044P (numbered according to SEQ ID NO: 115). Furthermore, the modified S protein may have the following substitutions: R654A, F786P, A861P, A868P, S911P, K P and V956P (numbered according to SEQ ID NO: 114) or R730A, R733G, A872P, S949P, A956P, N999P, V1043P and L1044P (numbered according to SEQ ID NO: 115).

Replacement at location 923

The modified S protein as described herein may also include a substitution, modification or mutation corresponding to position 923 (numbered according to SEQ ID NO: 2). For example, the amino acid corresponding to position 923 can be substituted with phenylalanine (F) or a conservative substitution of phenylalanine (F).

As shown in fig. 11B, the modified S protein with the "GSAS-2P" modification and the L923F substitution (expressed from construct 8933) showed a 1.36 fold increase in the yield of S protein compared to the yield of the "GSAS-2P" S protein without the L923F substitution (expressed from construct 8671). The modified S protein with the "GSAS-4P" modification and the L923F substitution (expressed from construct 8960) showed a 2.88 fold increase in the yield of the modified S protein compared to the yield of the "GSAS-2P" S protein without the L923F substitution (expressed from construct 8671). The modified S protein with the "GSAS-6P" modification and the L923F substitution (expressed from construct 8947) showed a 2.47 fold increase in the yield of the modified S protein compared to the yield of the "GSAS-2P" S protein without the L923F substitution (expressed from construct 8671).

Thus, the modified S protein may comprise one or more substitutions, wherein the one or more substitutions comprise a sequence corresponding to the sequence set forth in SEQ ID NO:2, or a combination thereof, at positions 667, 668, 670, 927, 971, 972, 802, 877, 884, 923. For example, the modified S protein may comprise or consist of one or more substitutions, wherein the one or more substitutions comprise or consist of one or more amino acid substitutions corresponding to the amino acid sequence of SEQ ID NO:2 (GSAS-2P-923), amino acids 667, 668, 670, 971, 972, 923, or combinations thereof, SEQ ID NO:2 (GSAS-4P-923), or amino acids of positions 667, 668, 670, 927, 971, 972, 802, 923 or combinations thereof, or SEQ ID NO:2 (GSAS-6P-923), 667, 668, 670, 927, 971, 972, 802, 877, 884, 923, or combinations thereof.

For example, the modified S protein may comprise or consist of one or more substitutions comprising or consisting of an amino acid corresponding to an amino acid at the following positions:

-SEQ ID NO: 667, 668, 670, 971, 972 and 923 of 2 (GSAS-2P-923)

-SEQ ID NO: 667, 668, 670, 927, 971, 972, 802 and 923 of 2 (GSAS-4P-923), or

-SEQ ID NO: 667, 668, 670, 927, 971, 972, 802, 877, 884 and 923 of 2 (GSAS-6P-923).

For example, the modified S protein may have an amino acid sequence that has about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween to the amino acid sequence of seq id no: SEQ ID NO:50 or SEQ ID NO:50, wherein the amino acid sequence has a glycine (G) or a conservative substitution of glycine (G) at position 667, a serine (S) or a conservative substitution of serine (S) at positions 668 and 670, a proline (P) or a conservative substitution of proline (P) at positions 971 and 972, and a phenylalanine (F) or a phenylalanine (F) at position 923; SEQ ID NO:51 or SEQ ID NO:51, wherein the amino acid sequence has glycine (G) or a conservative substitution of glycine (G) at position 667, serine (S) or a conservative substitution of serine (S) at positions 668 and 670, proline (P) or a conservative substitution of proline (P) at positions 927, 971, 972 and 802, and phenylalanine (F) or a conservative substitution of phenylalanine (F) at position 923; or SEQ ID NO:52 or SEQ ID NO:52, wherein the amino acid sequence has a glycine (G) or a conservative substitution of glycine (G) at position 667, a serine (S) or a conservative substitution of serine (S) at positions 668 and 670, a proline (P) or a conservative substitution of proline (P) at positions 927, 971, 972, 802, 877 and 884, and a phenylalanine (F) or a conservative substitution of phenylalanine (F) at position 923, wherein the modified S protein forms a VLP upon expression.

Thus, a modified coronavirus S protein is provided, which may include:

1. chimeric transmembrane and cytoplasmic tail domains (TMCT);

2. one or more substitutions of amino acids corresponding to positions 667, 668 and/or 670 (numbered according to SEQ ID NO: 2) as compared to the corresponding wild-type coronavirus S protein;

3. one or more substitutions corresponding to amino acids at positions 802, 877, 884, 927, 971 and/or 972 (numbered according to SEQ ID NO: 2) compared to the corresponding wild-type coronavirus S protein;

4. substitutions at position 923 (numbered according to SEQ ID NO: 2) as compared to the corresponding wild-type coronavirus S protein;

or, 5. Combinations of modifications and/or substitutions as described in 1-4.

As used herein, the terms "conservative substitutions" or "conservative substitutions" and grammatical variations thereof refer to amino acids that differ from a reference amino acid (substitutions) but that belong to the same class as the recited substitutions or recited residues (i.e., nonpolar residues replace nonpolar residues, aromatic residues replace aromatic residues, polar uncharged residues, charged residues replace charged residues). Other information about conservative substitutions can be found, for example, in Sahin-Toth et al (Protein ScL,3:240-247,1994), hochuli et al (Bio/Technology, 6:1321-1325,1988), henikoff S, and Henikoff JG (Proc. Natl. Acad. Sci. USA 89:10915-10919,1992), and widely used textbooks of genetics and molecular biology.

The modified viral structural proteins may also be further glycosylated. The coronavirus S protein, coronavirus M protein and coronavirus E protein are glycosylated, with N-linked glycosylation and O-linked glycosylation occurring simultaneously.

The modified viral structural protein may include a type of glycosylation unique to the host or host cell in which the modified viral structural protein is expressed. For example, when expressed in a plant or plant cell, the modified viral structural protein may comprise a plant-specific N-glycan. Thus, modified viral structural proteins having plant-specific N-glycans are also provided.

As described herein, the cytoplasmic tail domain (CT) of the modified viral structural protein can be replaced with CT from influenza Hemagglutinin (HA). The extracellular domain and transmembrane domain (TM) of the viral structural proteins described above are fused to the influenza HA cytoplasmic tail domain (CT) such that the CT is heterologous with respect to the extracellular domain and transmembrane domain of the viral structural proteins (e.g., S protein). The modified S protein can self-assemble into virus-like particles (VLPs).

Thus, the present description further relates to virus-like particles (VLPs). More specifically, the present description relates to VLPs comprising modified viral structural proteins (e.g., modified S proteins) and methods of producing VLPs having modified viral structural proteins (e.g., modified S proteins) in a host or host cell. VLPs include modified viral structural proteins, such as modified S proteins described herein.

As shown in fig. 6C, 17A, 17B and 17C, the modified viral structural proteins are illustrated by modified S proteins (modified SARS-CoV-2 or modified SARS-CoV-1S proteins), wherein natural or wild-type CT HAs been replaced with CT from self-assembly of influenza HA proteins into VLPs when expressed in plants. VLPs are similar to VLPs produced in the same plant expression system with either an S protein with native TM/CT sequence (see fig. 6A and 17A) or a modified S protein with H5 influenza TM/CT sequence (see fig. 6B and 17B).

In addition, as shown in fig. 6D, 6E, 6F and 6G, modified S proteins with variable edges or boundaries (intermediate peptide sequences) between TM and influenza CT domains also self-assemble into VLPs when expressed in plants.

Furthermore, as shown in fig. 6H, 6I, 6J, 6K, 6L and 6M, the modified S protein also self-assembles into VLPs when expressed in plants, where natural or wild-type CT HAs been replaced with CT of influenza HA proteins from H1, H3, H6, H7, H9 and B influenza, respectively.

In addition, as shown in FIGS. 19B-19F, 23B-23E, and 25A-25E, modified S proteins derived from MERS-CoV, OC43-CoV, and 229E-CoV also form VLPs, where the modified S proteins have TMCT from influenza H5 HA (H5 iTMCT), CT from influenza H5 HA (H5 iCT), or CT from influenza H1 HA.

The term "virus-like particle" (VLP) or "plurality of virus-like particles" or "VLPs" refers to virus-like structures that are generally similar in morphology and antigenicity to the virus particles produced in an infection, but lack sufficient genetic information to replicate and are therefore non-infectious. VLPs are self-assembled structures and include one or more structural proteins, such as, for example, modified viral structural proteins, such as, but not limited to, modified S proteins. Thus, VLPs may comprise modified S proteins. VLPs may also include viral structural proteins, wherein the viral structural proteins consist of modified S proteins. Thus, in some embodiments, VLPs may lack or be free of coronavirus M protein and/or coronavirus E protein. In some embodiments, VLPs produced from modified viral structural proteins as described herein therefore do not include coronavirus M protein, coronavirus E protein, or coronavirus M protein and coronavirus E protein. Furthermore, in some embodiments, the VLP does not include structural or nonstructural proteins from viruses heterologous to the coronaviridae or influenza viruses, e.g., the VLP does not include structural and nonstructural proteins from viruses other than from the coronaviridae.

In another embodiment, VLPs may include coronavirus E proteins, coronavirus M proteins, and modified coronavirus S proteins. In another embodiment, the VLP may include coronavirus E proteins and modified coronavirus S proteins. In another embodiment, VLPs may include coronavirus M proteins and modified coronavirus S proteins. Furthermore, VLPs may include coronavirus E proteins, modified coronavirus M proteins, and modified coronavirus S proteins. VLPs may also include modified coronavirus E proteins, modified coronavirus M proteins, and modified coronavirus S proteins. In another embodiment, the VLP may include a modified coronavirus E protein and a modified coronavirus S protein. In another embodiment, the VLP may include a modified coronavirus M protein and a modified coronavirus S protein.

VLPs may be produced in a suitable host or host cell (including plants and plant cells). After extraction from the host or host cell and isolation and further purification under appropriate conditions, VLPs may be recovered as intact structures.

VLPs may be purified or extracted using any suitable method, such as chemical or biochemical extraction. VLPs are relatively sensitive to drying, heat, pH, surfactants and detergents. Thus, methods are used to maximize yield, minimize contamination of VLP fractions by cellular proteins, maintain the integrity of the protein or VLP, and, if desired, the associated lipid envelope or membrane Methods of loosening the cell wall to release the protein or VLP may be useful. Minimizing or eliminating the use of detergents or surfactants, such as, for example, SDS or Triton ^TM X-100 may be advantageous for improving VLP extraction yield. The structure and size of VLPs can then be assessed, for example, by electron microscopy (see fig. 4B) or by size exclusion chromatography.

For enveloped viruses, such as coronaviruses, it may be advantageous for the lipid layer or membrane to be preserved by the virus. The composition of the lipids can vary systematically (e.g., plant-produced enveloped viruses will contain plant lipids or plant sterols in the envelope) and can help improve the immune response.

Thus, VLPs produced in a host or host cell may comprise lipids from the plasma membrane of the host or host cell. For example, VLPs produced in plants may include plant-derived lipids ("plant lipids"), VLPs produced in insect cells may include lipids from the plasma membrane of insect cells (commonly referred to as "insect lipids"), and VLPs produced in mammalian cells may include lipids from the plasma membrane of mammalian cells (commonly referred to as "mammalian lipids").

The plant lipids or plant-derived lipids may be in the form of lipid bilayers and may also include an envelope surrounding the VLP. The plant-derived lipids may include lipid components of the plasma membrane of the plant that produces the VLP, including phospholipids, triglycerides, diglycerides, and monoglycerides, as well as fat-soluble sterols or metabolites comprising sterols. Examples include Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol, phosphatidylserine, glycosphingolipids, phytosterols, or combinations thereof. Examples of phytosterols include campesterol, stigmasterol, ergosterol, brassicasterol, delta-7-stigmasterol, delta-7-aveterol, daunosterol, sitosterol, 24-methylcholesterol, cholesterol, or beta-sitosterol. As will be appreciated by those skilled in the art, the lipid composition of the cytoplasmic membrane may vary depending on the culture or growth conditions of the cell or organism or species from which the cell is obtained. In general, β -sitosterol is the most abundant phytosterol.

Without wishing to be bound by theory, plant-produced VLPs comprising plant-derived lipids may elicit a stronger immune response than VLPs produced in other production systems, and these plant-produced VLPs may elicit a stronger immune response than those elicited by live or attenuated whole virus vaccines.

Furthermore, in addition to the potential adjuvant effect of plant lipids, the ability of plant N-glycans to promote capture of glycoprotein antigens by antigen presenting cells may be beneficial for VLP production in plants.

VLPs produced within plants may include modified viral structural proteins, including plant-specific N-glycans. Accordingly, the present disclosure also provides VLPs comprising modified viral structural proteins with plant-specific N-glycans. Furthermore, VLPs comprising plant lipids and modified viral structural proteins with plant-specific N-glycans are provided.

Methods of producing virus-like particles (VLPs) comprising modified structural proteins in a host or host cell are also provided. In addition, methods of increasing the production yield of virus-like particles (VLPs) comprising modified structural proteins in a host or host cell are provided. These methods comprise introducing a nucleic acid comprising a sequence encoding a modified structural protein into a host or host cell and culturing the host or host cell under conditions that allow expression of the nucleic acid, thereby producing the VLP. The modified viral structural proteins may be produced in higher yields than a host or host cell expressing the unmodified viral structural proteins.

For example, as shown in fig. 3A, the yield of VLPs expressed in a plant may be increased when the Cytoplasmic Tail (CT) of the viral structural protein is replaced with CT of influenza HA to produce a modified viral structural protein, such as, for example, a modified S protein. As further shown in fig. 11A and 11B, when the modified S protein further comprises one or more substitutions, wherein the one or more substitutions comprise a sequence corresponding to SEQ ID NO:2, or one or more substitutions or consists of amino acids at positions 667, 668, 670, 802, 923, 927, 971 and/or 972, the yield of VLPs comprising modified S protein may be further increased when expressed in a plant.

The yield of a modified viral structural protein (such as a modified S protein) or VLP comprising a modified viral structural protein produced in a host or host cell, such as, for example, a plant or plant cell, may be increased by a factor of 1.1-10, or any amount in between, when compared to the yield of the corresponding unmodified viral structural protein or VLP comprising the corresponding unmodified viral structural protein. For example, when compared to the yield of the corresponding unmodified viral structural protein or the yield of VLPs wherein the VLP comprises the corresponding unmodified viral structural protein when produced in the host or host cell under the same conditions, the yield of a modified viral structural protein (e.g., modified S protein) or VLP (including modified viral structural protein) in a host or host cell may be increased by 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6 4.7, 4.8, 4.9, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 8, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 9, 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8, 9.9, 10 times or any amount therebetween.

The modified viral structural proteins described herein include modified S proteins having an amino acid sequence that hybridizes to SEQ ID NO: 1. 2, 5, 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 112, 113, 114, 115, 144, 145, 146, 155, 156, 157, 158, 159, 160 or 161, or an amino acid sequence identical to SEQ ID NO:47, amino acids 25-1259, SEQ ID NO:48, amino acids 25-1259, SEQ ID NO:49, amino acids 25-1259, SEQ ID NO:50, amino acids 25-1259, SEQ ID NO:51, amino acids 25-1259, SEQ ID NO:52, amino acids 25-1259, SEQ ID NO:53, amino acids 25-1259, SEQ ID NO:54, amino acids 25-1259, SEQ ID NO:55, amino acids 25-1259, SEQ ID NO:56, amino acids 25-1259, SEQ ID NO:57, amino acids 25-1259, SEQ ID NO:58, amino acids 25-1259, SEQ ID NO:59, amino acids 25-1262, SEQ ID NO:60, amino acids 25-1261, SEQ ID NO:61, amino acids 25-1258, SEQ ID NO:62, amino acids 25-1256, SEQ ID NO:95, amino acids 25-1243, SEQ ID NO:96, amino acids 25-1240, SEQ ID NO:97, amino acids 25-1243, SEQ ID NO:108, amino acids 25-1341, SEQ ID NO:109, amino acids 25-1338, SEQ ID NO:110, amino acids 25-1341, SEQ ID NO:144, amino acids 25-1351, SEQ ID NO:145, amino acids 25-1348, SEQ ID NO:146, amino acids 25-1351, SEQ ID NO:155, amino acids 25-1159, SEQ ID NO:156 or amino acids 25-1156 of SEQ ID NO:157 has about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, and wherein the modified S protein forms a VLP when expressed in a host or host cell. The amino acid sequences of the extracellular domain and the transmembrane domain of the modified S protein correspond to the amino acid sequences of SEQ ID NO:1, amino acids 1-1234, amino acid sequence corresponding to SEQ ID NO:2, amino acids 1-1219, and SEQ ID NO:5, amino acids 1-1234, amino acid sequence identical to SEQ ID NO:21, amino acids 1-1219, and SEQ ID NO:30, amino acids 1-1243, amino acids corresponding to SEQ ID NO:47, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:48, amino acids 25-1243, amino acids corresponding to SEQ ID NO:49, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:50, amino acids 25-1243, amino acids corresponding to SEQ ID NO:51, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:52, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:53, amino acids 25-1243, and SEQ ID NO:54, amino acids 25-1243, amino acids corresponding to SEQ ID NO:55, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:56, amino acids 125-1243, SEQ ID NO:57, amino acids 25-1243, SEQ ID NO:58, amino acids 25-1243, amino acids corresponding to SEQ ID NO:59, amino acids 25-1242, and SEQ ID NO:60, amino acids 25-1242, amino acid sequence corresponding to SEQ ID NO:61, amino acids 25-1246, or amino acid sequence corresponding to SEQ ID NO:62, amino acids 25-1245, SEQ ID NO:95, amino acids 25-1227, SEQ ID NO:96, amino acids 25-1227, SEQ ID NO:97, amino acids 25-1227, SEQ ID NO:108, amino acids 25-1325, SEQ ID NO:109, amino acids 25-1325, SEQ ID NO:110, amino acids 25-1325, SEQ ID NO:144, amino acids 25-1335, SEQ ID NO:145, amino acids 25-1335, SEQ ID NO:146, amino acids 25-1335 of SEQ ID NO:155, amino acids 25-1143, SEQ ID NO:156 or amino acids 25-1143 of SEQ ID NO:157 from amino acids 25 to 1143 of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, and the amino acid sequence of the cytoplasmic tail domain (CT) of the modified S protein is identical to SEQ ID NO:15 or a sequence identical to SEQ ID NO: 6. 8, 7, 9, 10, 12, 13, 14 or amino acids 35-50 or amino acids identical to SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3, and wherein the modified S protein forms VLPs when expressed in a host or host cell, has 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

Furthermore, the modified viral structural protein may be encoded by a nucleotide sequence that hybridizes to a sequence according to SEQ ID NO: 22. 26, 29, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 90, 91, 92, 95, 96, 97, 103, 104, 105, 139, 140, 141, 150, 151 or 152, and wherein the nucleotide sequence encodes a modified S protein that forms a VLP when expressed in a host or host cell has about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount sequence identity or sequence similarity therebetween.

Also provided are nucleotide sequences encoding modified S proteins having a nucleotide sequence that matches SEQ ID NO: 1. 2, 5, 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 144, 145, 146, 155, 156, or 157 has an amino acid sequence of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, and wherein the modified S protein forms a VLP when expressed in a host or host cell. The nucleotide sequence may encode the amino acid sequences of the extracellular domain and transmembrane domain of the modified S protein, which hybridizes with the amino acid sequence of SEQ ID NO:1, amino acids 1-1234, amino acid sequence corresponding to SEQ ID NO:2, amino acids 1-1219, and SEQ ID NO:5, amino acids 1-1234, amino acid sequence identical to SEQ ID NO:21 or amino acids 1-1219 or amino acid sequence corresponding to SEQ ID NO:30, amino acids 1-1243, amino acids corresponding to SEQ ID NO:47, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:48, amino acids 25-1243, amino acids corresponding to SEQ ID NO:49, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:50, amino acids 25-1243, amino acids corresponding to SEQ ID NO:51, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:52, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:53, amino acids 25-1243, and SEQ ID NO:54, amino acids 25-1243, amino acids corresponding to SEQ ID NO:55, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:56, amino acids 25-1243, amino acid sequence corresponding to SEQ ID NO:57, amino acids 25-1243, amino acids corresponding to SEQ ID NO:58, amino acids 25-1243, amino acids corresponding to SEQ ID NO:59, amino acids 25-1242, and SEQ ID NO:60, amino acids 25-1242, amino acid sequence corresponding to SEQ ID NO:61, amino acids 25-1246, amino acid sequence corresponding to SEQ ID NO:62, amino acids 25-1245, amino acid sequence corresponding to SEQ ID NO:95, amino acids 25-1227, amino acid sequence corresponding to SEQ ID NO:96, amino acids 25-1227, amino acids corresponding to SEQ ID NO:97, amino acids 25-1227, amino acid sequence corresponding to SEQ ID NO:108, amino acids 25-1325, and SEQ ID NO:109, amino acids 25-1325, amino acid sequence of SEQ ID NO:110, amino acids 25-1325, and SEQ ID NO:144, amino acids 25-1335, and SEQ ID NO:145, amino acids 25-1335, amino acids corresponding to SEQ ID NO:146, amino acids 25-1335, and SEQ ID NO:155, amino acids 25-1143, amino acid sequence corresponding to SEQ ID NO:156, amino acids 25-1143, amino acid sequence corresponding to SEQ ID NO:157 from amino acids 25 to 1143 of about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, and the amino acid sequence of the cytoplasmic tail domain of the modified S protein is identical to SEQ ID NO:15, or a sequence identical to SEQ ID NO: 6. 8, 7, 9, 10, 12, 13, 14, or amino acids 35-50, or amino acids identical to SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3, and wherein the modified S protein forms a VLP when expressed in a host or host cell, has about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween.

Also provided are nucleotide sequences encoding modified S proteins having a nucleotide sequence that matches SEQ ID NO: 5. 21, 30 or 47-62, or an amino acid sequence that hybridizes with SEQ ID NO:47, amino acids 24-1259, seq ID NO:48, amino acids 25-1259, seq ID NO:49, amino acids 25-1259, seq ID NO:50, amino acids 25-1259, seq ID NO:51, amino acids 25-1259, seq ID NO:52, amino acids 25-1259, seq ID NO:53, amino acids 25-1259, seq ID NO:54, amino acids 25-1259, seq ID NO:55, amino acids 25-1259, seq ID NO:56, amino acids 25-1259, seq ID NO:57, amino acids 25-1259, seq ID NO:58, amino acids 25-1259, seq ID NO:59, amino acids 25-1262, seq ID NO:60, amino acids 25-1261, seq ID NO:61, amino acids 25-1258, seq ID NO:62, amino acids 25-1256, seq ID NO:95, amino acids 25-1243, seq ID NO:96, amino acids 25-1240, seq ID NO:97, amino acids 25-1243, seq ID NO:108, amino acids 25-1341, seq ID NO:109, amino acids 25-1338, seq ID NO:110, amino acids 25-1341, seq ID NO:144, amino acids 25-1351, seq ID NO:145, amino acids 25-1348, seq ID NO:146, amino acids 25-1351, seq ID NO:155, amino acids 25-1159 of seq ID NO:156, amino acids 25-1156, seq ID NO:157 has about 70, 75, 80, 85, 87, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% or any amount of sequence identity or sequence similarity therebetween, and wherein the modified S protein forms a VLP when expressed in a host or host cell.

When referring to a particular sequence, the terms "percent similarity", "sequence similarity", "percent identity" or "sequence identity" are used, for example, as described in the university of wisconsin GCG software program, or by manual alignment and visual inspection (see, e.g., current Protocols in Molecular Biology, supplement to Ausubel et al, main edition 1995). Sequence alignment methods for comparison are well known in the art. The optimal sequence alignment for comparison may be implemented using, for example, the following algorithm: the Smith & Waterman algorithm (1981, adv. Appl. Math. 2:482), the Needleman & Wunsch alignment algorithm (1970, J. Mol. Biol. 48:443), the Pearson & Lipman search similarity method (1988,Proc.Natl.Acad.Sci.USA 85:2444), computerized implementation of these algorithms (e.g., GAP, BESTFIT, FASTA and TFASTA, genetics Computer Group (GCG) in Wisconsin Genetics packages, 575Science Dr., madison, wis.).

Examples of algorithms suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al (1977,Nuc.Acids Res.25:3389-3402) and Altschul et al (1990, J. Mol. Biol. 215:403-410), respectively. The percent sequence identity of the nucleic acids and proteins disclosed herein are determined using BLAST and BLAST 2.0 and with the parameters described herein. For example, the BLASTN program (for nucleotide sequences) can use a 11 word length (W), a 10 expected value (E), m=5, n= -4, and default values for two strand comparisons. For amino acid sequences, the BLASTP program can use the word length=3, the expected value (E) =10, and the deletion values of the BLOSUM62 scoring matrix (see Henikoff & Henikoff,1989,Proc.Natl.Acad.Sci.USA 89:10915), the alignment (B) =50, the expected value (E) =10, m=5, n= -4, and the deletion values of the two strand comparisons. The software for performing BLAST analysis is publicly available through the national center for Biotechnology information (National Center for Biotechnology Information) (see URL: ncbi.nlm.nih.gov /).

A nucleic acid sequence or nucleotide sequence referred to in the present disclosure may be "substantially homologous", "substantially similar" or "substantially identical" to a sequence or complement of a sequence, if the sequence hybridizes to one or more than one nucleotide sequence or complement of a sequence as defined herein under stringent hybridization conditions. Sequences are "substantially homologous," "substantially similar," or "substantially identical" when at least about 70%, or between 70% and 100%, or any amount therebetween, e.g., 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100%, or any amount therebetween, of nucleotides match over a defined length of nucleotide sequence, so long as the homologous sequences exhibit one or more characteristics of the sequences or encoded products as described herein.

A variety of organisms exhibit a preference for using specific codons to encode the insertion of specific amino acids in a growing peptide chain. Codon preference or codon bias (differences in codon usage between organisms) is provided by the degeneracy of the genetic code and is well documented in a variety of organisms. Codon bias is generally related to the efficiency of translation of messenger RNA (mRNA), which in turn is believed to depend on the nature of the codon being translated, availability of particular transfer RNA (tRNA) molecules, and the like. The dominance of the selected tRNA in the cell generally reflects codons most commonly used in peptide synthesis. Thus, based on codon optimisation, genes can be regulated for optimal gene expression in a given organism. The optimization of nucleotide sequences encoding heterologous expressed proteins may be an important step in improving expression yields. The optimization requirements may include a step of improving the ability of the host to produce the exogenous protein.

Different codon optimization techniques are known in the art for improving the translational kinetics of protein coding regions where translation is inefficient. These techniques rely primarily on the use of codons to identify certain host organisms. If a gene or sequence should be expressed in the organism, the coding sequences for these genes and sequences will be modified so that one will replace the codons of the sequence of interest with codons more commonly used in the host organism.

"codon optimization" is defined as modifying a nucleic acid sequence to enhance expression in a host or host cell of interest by replacing at least one, more than one, or a large number of codons of the native sequence, which codons may be more or most commonly used in genes of another organism or species. Various species show a specific bias for a particular codon for a particular amino acid.

The present disclosure includes synthetic polynucleotide sequences that have been codon optimized, e.g., sequences that have been optimized for human codon usage or plant codon usage. The codon optimized polynucleotide sequence can then be expressed in a host, such as a plant. More specifically, sequences optimized for human codon usage or plant codon usage may be expressed in plants. Without wishing to be bound by theory, it is believed that the sequence optimized for human codons increases the guanine-cytosine content (GC content) of the sequence and improves expression yield when the plant is used as a host.

As used herein, the term "construct," "vector," or "expression vector" refers to a recombinant nucleic acid for transferring an exogenous nucleotide sequence (e.g., a nucleotide sequence encoding a modified viral structural protein as described herein) to a host cell (e.g., a plant cell) and directing expression of the exogenous nucleic acid sequence in the host cell. An "expression cassette" refers to a nucleic acid comprising a nucleotide sequence of interest under the control of and operably linked to a suitable promoter or other regulatory element for transcription of the nucleic acid of interest in a host cell. As will be appreciated by those of skill in the art, an expression cassette may comprise a terminator sequence, which is any sequence active in a host cell (e.g., a plant host). For example, in plants, the termination sequence may be derived from an RNA-2 genomic segment of a binary RNA virus, e.g., cowpea mosaic virus, the termination sequence may be a NOS terminator, or the termination sequence may be derived from the 3' utr of the alfalfa plastocyanin gene.

As described herein, a nucleic acid comprising a nucleotide sequence encoding a modified viral structural protein may also comprise a sequence that enhances expression of the viral structural protein in a host, a portion of a host, or a host cell. The expression enhancing sequence may comprise a 5' utr enhancer element, or a plant-derived expression enhancer, which is operably linked to a nucleic acid encoding the modified viral structural protein. The sequences encoding the modified viral structural proteins can also be optimized to increase expression, for example, by optimizing human codon usage, increasing GC content, or a combination thereof.

"regulatory region", "regulatory element" or "promoter" means the portion of nucleic acid that is usually, but not always, upstream of the protein coding region of a gene, and which may consist of DNA or RNA, or of both DNA and RNA. When the regulatory region is active and operably associated or operably linked to a nucleotide sequence of interest, this may result in expression of the nucleotide sequence of interest. Regulatory elements may be capable of mediating organ specificity, or controlling development or temporal gene activation. "regulatory region" includes promoter elements, core promoter elements exhibiting basal promoter activity, inducible elements responsive to external stimuli, elements mediating promoter activity, such as negative regulatory elements or transcriptional enhancers. As used herein, a "regulatory region" also includes elements that are active post-transcriptionally, e.g., regulatory elements that regulate gene expression, such as translation and transcription enhancers, translation and transcription repressors, upstream activating sequences, and mRNA instability determinants. Several of these latter elements may be located near the coding region.

In the context of the present disclosure, the term "regulatory element" or "regulatory region" generally refers to a DNA sequence that is generally, but not always, upstream (5') of the coding sequence of a structural gene that controls expression of the coding region by providing for the recognition of RNA polymerase and/or other factors required to initiate transcription at a particular site. However, it will be appreciated that other nucleotide sequences located within an intron or at the 3' end of the sequence may also be useful in regulating expression of the coding region of interest. An example of a regulatory element that provides for the recognition of RNA polymerase or other transcription factors to ensure initiation at a particular site is a promoter element. Most, but not all, eukaryotic promoter elements contain a TATA box, which is a conserved nucleic acid sequence consisting of adenosine and thymidine nucleotide base pairs, typically located about 25 base pairs upstream of the transcription initiation site. The promoter element may comprise a basic promoter element responsible for transcription initiation and other regulatory elements that alter gene expression.

There are several types of regulatory regions, including developmental regulatory, inducible or constitutive regulatory regions. At a particular time during development of certain organs or tissues, regulatory regions of developmental regulation or control of differential expression of genes under their control are activated within the organ or tissue. However, some of the developmentally regulated regulatory regions may be preferentially active in certain organs or tissues at a particular developmental stage, they may also be active in a developmentally regulated manner, or may also be at basal levels in other organs or tissues within the plant. Examples of tissue-specific regulatory regions (e.g., seed-specific regulatory regions) include the napin promoter and the cresselin promoter (Rask et al 1998,J.Plant Physiol.152:595-599; bilodeau et al 1994,Plant Cell 14:125-130). Examples of leaf-specific promoters include the plastocyanin promoter (see US 7,125,978, incorporated herein by reference).

Inducible regulatory regions are regulatory regions capable of directly or indirectly activating one or more DNA sequences or genes in response to an inducer. In the absence of an inducer, the DNA sequence or gene will not be transcribed. In general, a protein factor that specifically binds to an inducible regulatory region to activate transcription may exist in an inactive form and then be converted directly or indirectly to an active form by an inducer. However, protein factors may also be absent. The inducer may be a chemical agent such as a protein, metabolite, growth regulator, herbicide or phenolic compound, or a physiological stress applied directly by heat, cold, salt or toxic elements or indirectly by the action of a pathogen or disease agent, such as a virus. Plant cells comprising the inducible regulatory region may be exposed to the inducer by externally applying the inducer to the cell or plant, for example by spraying, watering, heating or the like. The inducible regulatory element may be derived from a plant or non-plant gene (e.g., gatz, C.and Lenk, I.R.P.,1998,Trends Plant Sci.3,352-358). Examples of potential inducible promoters include, but are not limited to, tetracycline-inducible promoters (Gatz, C.,1997,Ann.Rev.Plant Physiol.Plant Mol.Biol.48,89-108), steroid-inducible promoters (Aoyama, T.and Chua, N.H.,1997,Plant J.2,397-404) and ethanol-inducible promoters (Salter, M.G., et al, 1998,Plant Journal16,127-132; cadrick, M.X., et al, 1998,Nature Biotech.16,177-180), cytokinin-inducible IB6 and CKI1 genes (Brandstatter, I.and Kieber, J.J.,1998,Plant Cell 10,1009-1019; kakimoto, T.,1996,Science 274,982-985), and an auxin-inducible element DR5 (Ulmasov, T., et al, 1997,Plant Cell 9,1963-1971).

The constitutive regulatory regions direct gene expression at different parts of a plant and continue to be expressed during plant development. Examples of known constitutive regulatory elements include promoters associated with CaMV 35S transcripts. (p 35S; odell et al, 1985, nature,313:810-812; this document is incorporated herein by reference), rice actin 1 (Zhang et al, 1991,Plant Cell,3:1155-1165), actin 2 (An et al, 1996, plant J., 10:107-121) or tms 2 (U.S. 5,428, 147) and triose phosphate isomerase 1 (Xu et al, 1994,Plant Physiol.106:459-467) genes, maize ubiquitin 1 gene (Cornejo et al, 1993,Plant Mol.Biol.29:637-646), arabidopsis ubiquitin 1 and 6 genes (Holtorf et al, 1995,Plant Mol.Biol.29:637-646), tobacco translation initiation factor 4A gene (Mandel et al, 1995Plant Mol.Biol.29:995-1004), cassava vein mosaic virus promoter AS (Verdaguer et al, 1996); the ribulose bisphosphate carboxylase small subunit promoter pRbcS: (Outchkourov et al, 2003), pUbi (for monocots and dicots).

The term "constitutive" as used herein does not necessarily mean that the nucleotide sequence is expressed at the same level in all cell types under the control of constitutive regulatory regions, but that the sequence is expressed in a wide range of cell types even if changes in abundance are often observed.

The one or more genetic constructs disclosed herein may also include other enhancers, i.e., translational or transcriptional enhancers, as desired. Enhancers may be located 5 'or 3' to the transcribed sequence. Enhancer regions are well known to those skilled in the art and may include the ATG start codon, adjacent sequences, and the like. The initiation codon, if present, may be in-phase with the reading frame of the coding sequence ("in-frame") to provide for proper translation of the transcribed sequence.

The term "5'UTR" or "5' untranslated region", "5 'leader sequence" or "5' UTR enhancer element" refers to an untranslated mRNA region. The 5' UTR typically starts at the transcription initiation site and ends before the translation initiation site or start codon of the coding region. The 5' utr may regulate stability and/or translation of mRNA transcripts.

As used herein, the term "plant-derived expression enhancer" refers to a nucleotide sequence derived from a plant, a nucleotide sequence encoding a 5' utr. Examples of plant-derived expression enhancers are described in U.S. provisional patent application No.62/643,053 (filed on day 14 of 3.2018) and International application No. PCT/CA2019/050319 (filed on day 14 of 3.2019), which are incorporated herein by reference, or in Diamond A.G et al (2016,Front Plt Sci.7:1-15; which is incorporated herein by reference). Plant-derived expression enhancers may be selected from the group consisting of nbEPI42, nbSNS46, nbCSY65, nbHEL40, nbSEP44, nbMT78, nbATL75, nbDJ46, nbCSHP 79, nbEN42, atHSP69, atGRP62, atPK65, atRP46, nb30S72, nbGT61, nbPV55, nbPPI43, nbPM64 and nbH A86 as described in U.S. Pat. No.62/643,053 and PCT/CA 2019/050319. The plant-derived expression enhancers can be used within a plant expression system that includes a regulatory region operably linked to the plant-derived expression enhancer sequence and a nucleotide sequence of interest (e.g., a nucleotide sequence encoding a modified S protein).

The stability and/or translation efficiency of RNA can be further improved by including a 3 'untranslated region (3' UTR). Thus, one or more genetic constructs of the present description may also include a 3' utr.

The 3' untranslated region may contain polyadenylation signals and any other regulatory signals capable of affecting mRNA processing or gene expression. Polyadenylation signals are generally characterized by affecting the addition of polyadenylation chains to the 3' end of the mRNA precursor. Polyadenylation signals are generally recognized by the presence of homology to the canonical form 5'AATAAA-3', although variations are not uncommon. Non-limiting examples of suitable 3 'regions are untranslated regions containing the following 3' transcripts: agrobacterium (Agrobacterium) tumor-inducing (Ti) plasmid genes, such as nopaline synthase (Nos gene) and plant genes, such as polyadenylation signals of soybean storage protein genes, ribulose-1, 5-bisphosphate carboxylase small subunit genes (ssRUBISCO; U.S. Pat. No. 4,962,028; incorporated herein by reference), promoters for use in regulating the expression of plastid bluein, are described in U.S. Pat. No. 5, 7,125,978 (incorporated herein by reference); 3' UTR (SEQ ID NO: 40) from Arracach virus B segregation gene (AvB), 3' UTR (SEQ ID NO: 41) from beet necrotic yellow vein virus (trBNYVV), 3' UTR (SEQ ID NO: 42) from Southern Bean Mosaic Virus (SBMV), 3' UTR (SEQ ID NO: 43) from turnip round spot virus (TuRSV), 3' UTR (SEQ ID NO: 44) from cowpea mosaic virus (CPMV), 3' UTR (SEQ ID NO: 45) from broad bean eukaryotic mosaic virus (BBTMV) or 3' UTR (SEQ ID NO: 46) from European melon virus (trOUMV). The 3'UTR may be used in combination with a 5' UTR derived from a heterologous sequence to regulate expression levels.

Thus, provided are "constructs," "vectors," "expression vectors," or "expression cassettes," which include nucleic acids comprising a nucleotide sequence of interest (e.g., a modified viral structural protein) under the control of and operably linked to a 3' utr. In addition, the nucleic acid can include a 3' UTR operably linked (or operably linked) to a nucleotide sequence of interest (e.g., a modified viral structural protein).

The modified viral structural protein may be targeted to any intracellular or extracellular space, organelle or tissue of the host of a host cell (e.g., plant or plant cell), as desired. In order to localize the expressed protein to a specific location, the nucleic acid encoding the protein may be linked to a nucleic acid sequence encoding a signal peptide or leader sequence. The signal peptide may alternatively be referred to as a transit peptide, signal sequence, leader sequence, targeting signal, localization sequence, transit peptide or leader peptide.

One or more modified genetic constructs of the present description may be expressed in any suitable host or host cell transformed with a nucleic acid, or nucleotide sequence, or construct or vector, as disclosed herein. The host or host cell may be from any source, including plants, fungi, bacteria, insects, and animals, e.g., mammals. Thus, the host or host cell may be selected from plants or plant cells, fungi or fungal cells, bacteria or bacterial cells, insect or insect cells, and animal or animal cells. The mammal or animal may not be a human. In a preferred embodiment, the host or host cell is a plant, a part of a plant or a plant cell.

As used herein, the terms "plant", "part of a plant", "plant part", "plant matter", "plant biomass", "plant material", "plant extract" or "plant leaf" may include whole plants, tissues, cells or any parts thereof, intracellular plant components, extracellular plant components, liquid or solid extracts of plants or combinations thereof, which are capable of providing transcriptional, translational and posttranslational mechanisms for expression of one or more of the nucleic acids described herein, and/or from which expressed proteins or VLPs may be extracted and purified. Plants may include, but are not limited to, herbaceous plants. The herb may be an annual, biennial or perennial plant. Plants may also include, but are not limited to, crops including, for example, canola, brassica spp, corn, nicotiana spp (tobacco), such as Nicotiana benthamiana Nicotiana benthamiana, nicotiana tabacum Nicotiana rustica, nicotiana Nicotiana tabacum, nicotiana tabacum, arabidopsis thaliana Arabidopsis thaliana, alfalfa, potato, sweet potato, ginseng, pea, oat, rice, soybean, wheat, barley, sunflower, cotton, corn, rye (Secale cereale), sorghum (Sorghum bicolor), sorghum (Sorghum vulgare), safflower (Carthamus tinctorius).

As used herein, the term "plant part" refers to any plant part including, but not limited to, leaves, stems, roots, flowers, fruits, plant cells from leaves, stems, roots, flowers, fruits, plant extracts from leaves, stems, roots, flowers, fruits, or combinations thereof. In one embodiment, the plant part refers to an aerial part of a plant, such as (for example) leaves, stems, flowers and fruits. As used herein, the term "plant extract" refers to a plant-derived product obtained after treatment of a plant, plant part, plant cell, or combination thereof, either physically (e.g., by freezing, then extracting in a suitable buffer), mechanically (e.g., by grinding or homogenizing the plant or plant part, then extracting in a suitable buffer), enzymatically (e.g., using a cell wall degrading enzyme), chemically (e.g., using one or more chelating agents or buffers), or by a combination thereof. The plant extract may be further treated to remove undesirable plant components, such as cell wall debris. Plant extracts may be obtained to aid in the recovery of one or more components from a plant, plant part, or plant cell, for example, recovery of proteins (including protein complexes, protein superstructures, and/or VLPs), nucleic acids, lipids, carbohydrates, or combinations thereof from a plant, plant part, or plant cell. If the plant extract comprises a protein, it may be referred to as a protein extract. The protein extract may be a crude plant extract, a partially purified plant or protein extract, or a purified product comprising one or more proteins from plant tissue, protein complexes, such as, for example, protein trimers, protein superstructures, and/or VLPs. If desired, the protein extract or plant extract may be partially purified using techniques known to those skilled in the art, e.g., the extract may be subjected to salt or pH precipitation, centrifugation, gradient density centrifugation, filtration, chromatography, e.g., size exclusion chromatography, ion exchange chromatography, affinity chromatography, or combinations thereof. The protein extract may also be purified using techniques known to those skilled in the art.

The constructs disclosed herein can be introduced into plant cells using Ti plasmids, ri plasmids, plant viral vectors, direct DNA transformation, microinjection, electroporation, and the like. For a review of these techniques see, e.g., weissbach and Weissbach, methods for Plant Molecular Biology, academy Press, new York VIII, pages 421-463 (1988); geierson and Corey, plant Molecular Biology, version 2 (1988); and Miki and Iyer Fundamentals of Gene Transfer in plants in Plant Metabolism, 2 nd edition DT. Dennis, DH Turpin, DD Lefebvre, DB Layzell (Main works), addison Wesley, langmans Ltd. London, pages 561-579 (1997). Other methods include direct DNA introduction, use of liposomes, electroporation, e.g., using protoplasts, microinjection, microparticles or whiskers, and vacuum infiltration. See, for example, bilang et al (Gene 100:247-250 (1991)), scheid et al (mol. Gen. Genet.228:104-112, 1991), guerche et al (Plant Science 52:111-116,1987), neuhuse et al (Theor. Appl Genet.75:30-36,1987), klein et al (Nature 327:70-73 (1987)); howell et al (Science 208:1265, 1980), horsch et al (Science 227:1229-1231,1985), deBlock et al (Plant Physiology 91:694-701,1989), methods for Plant Molecular Biology (Weissbach and Weissbach Main plaited, academic Press Inc., 1988), methods in Plant Molecular Biology (Schuler and Zielinski Main plaited, academic Press Inc., 1989), liu and Lomonossoff (J Virol Meth,105:343-348,2002), U.S. Pat.No.4,945,050;5,036,006; and U.S. patent application Ser. No.08/438,666, filed 5,792, 5/10/1992, and U.S. patent application Ser. No.07/951,715, filed 9/25/1992, all of which are incorporated herein by reference.

As described below, transient expression methods may be used to express the disclosed constructs (see Liu and Lomonossoff,2002,Journal of Virological Methods,105:343-348; incorporated herein by reference). Alternatively, a vacuum-based transient expression method may be used, as described in Kapila et al, 1997, which is incorporated herein by reference. Such methods may include, for example, but are not limited to, methods of Agrobacterium inoculation or Agrobacterium infiltration, syringe infiltration, although other transient methods as described above may also be used. The mixture of Agrobacteria (Agrobacteria) comprising the desired nucleic acid is introduced into the interstitial space of the tissue by agroinoculation, agroinfiltration or syringe infiltration, for example the leaves, aerial parts (including stems, leaves and flowers) of the plant, other parts of the plant (stems, roots, flowers) or the whole plant. After passage through the epidermis, agrobacterium (Agrobacterium) infects and transfers copies of t-DNA into the cells. The t-DNA is transcribed as an episome and its mRNA translated, resulting in the production of the protein of interest in the infected cell, however, t-DNA is transient into the nucleus.

To aid in the identification of transformed plant cells, the constructs disclosed herein may also be manipulated to include plant selectable markers. Useful selectable markers include enzymes that provide resistance to chemicals such as antibiotics, e.g., gentamicin, hygromycin, kanamycin, or herbicides such as glufosinate, glyphosate, chlorsulfuron, and the like. Similarly, enzymes for producing compounds recognizable by a color change, such as GUS (β -uridylase), or by fluorescence, e.g., luciferase or GFP, may be used.

Transgenic plants, plant cells or seeds containing the disclosed genetic constructs are also considered part of the disclosure, which may be used as a platform plant suitable for transient protein expression as described herein. Methods for regenerating whole plants from plant cells are also known in the art (see, e.g., guerineau and Mullineaux (1993,Plant transformation and expression vectors.In:Plant Molecular Biology Labfax (Croy RRD ed) Oxford, BIOS Scientific Publishers, pages 121-148)). Typically, the transformed plant cells are cultured in a suitable medium, which may contain a selection agent, such as an antibiotic, wherein a selectable marker is used to facilitate recognition of the transformed plant cells. Once callus is formed, shoot formation can be promoted by using appropriate plant hormones according to known methods and the shoots transferred to rooting medium for plant regeneration. Plants can then be used to establish repeated generations from seeds or using vegetative propagation techniques. Transgenic plants can be produced without the use of tissue culture. Methods for stably transforming and regenerating these organisms are established in the art and are known to those skilled in the art. Available techniques are reviewed by Vasil et al (Cell Culture and Somatic Cell Genetics of Plants, volumes I, II and III, laboratory Procedures and Their Applications, academic Press, 1984) and Weissbach and Weissbach (Methods for Plant Molecular Biology, academic Press, 1989). The method of obtaining the transformed and regenerated plants is not critical to the present disclosure.

If a plant, plant part or plant cell is to be transformed or co-transformed with two or more nucleic acid constructs, the nucleic acid constructs may be introduced into Agrobacterium (Agrobacterium) in a single transfection event, thereby mixing the nucleic acids and transfecting the bacterial cells. Alternatively, the constructs may be introduced sequentially. In this case, as described, the first construct is introduced into Agrobacterium, and the cells are grown under selective conditions (e.g., in the presence of antibiotics) where only a single transformed bacterium can grow. After this first selection step, a second nucleic acid construct is introduced into Agrobacterium (agrobacteria) as described, and the cells are grown under dual selective conditions in which only dual transformed bacteria can grow. The doubly transformed bacteria may then be used to transform a plant, plant part or plant cell as described herein, or further transformation steps may be performed to house the third nucleic acid construct.

Alternatively, if a plant, plant part or plant cell is to be transformed or co-transformed with two or more nucleic acid constructs, the nucleic acid constructs may be introduced into the plant by co-infiltrating Agrobacterium cells (agrobacteria) with a mixture of plants, plant parts or plant cells, each Agrobacterium (agrobacteria) cell may comprise one or more constructs to be introduced into the plant. To alter the relative expression level of the nucleotide sequence of interest within the construct within the plant, plant part or plant cell, the concentration of the various Agrobacterium (Agrobacterium) populations comprising the desired construct may be altered during the infiltration step.

The modified viral surface proteins or VLPs comprising the modified viral surface proteins as described herein may be used to elicit an immune response in a subject.

An "immune response" generally refers to a response of the adaptive immune system of a subject. The adaptive immune system generally includes humoral immune responses and cell-mediated responses. Humoral immune responses are aspects of immunity mediated by secreted antibodies produced in cells of the B lymphocyte lineage (B cells). Secreted antibodies bind to antigens on the surface of invading microorganisms (e.g., viruses or bacteria), labeling them for destruction. Humoral immunity is generally used to represent antibody production and its accompanying processes, as well as effector functions of antibodies, including Th2 cell activation and cytokine production, memory cell production, opsonin promotion of phagocytosis, pathogen clearance, and the like. The term "modulate" and like terms refer to an increase or decrease in a particular response or parameter, as determined by any of several assays generally known or used, some of which are exemplified herein.

The cell-mediated response is an immune response that does not involve antibodies, but rather involves activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and release of multiple cytokines in response to the antigen. Cell-mediated immunity is generally used to represent certain Th cell activation, tc cell activation and T cell-mediated responses. Cell-mediated immunity may be particularly important in responding to viral infections.

For example, induction of antigen-specific CD 8-positive T lymphocytes can be measured using an ELISPOT assay; stimulation of CD4 positive T lymphocytes can be measured using proliferation assays. Anti-coronavirus antibody titers can be quantified using ELISA assays; isotypes of antigen-specific or cross-reactive antibodies can also be measured using anti-isotype antibodies (e.g., anti IgG, igA, igE or IgM). Methods and techniques for performing these assays are well known in the art.

The presence or level of an cytokine may also be quantified. For example, a T helper cell response (Th 1/Th 2) will be characterized by measurement of IFN-. Gamma.and IL-4 secreting cells by ELISA (e.g., BD Biosciences OptEIA kit). Peripheral Blood Mononuclear Cells (PBMCs) or spleen cells obtained from a subject may be cultured and the supernatant analyzed. T lymphocytes can also be quantified by Fluorescence Activated Cell Sorting (FACS) using marker specific fluorescent markers and methods known in the art.

A trace neutralization assay can also be performed to identify immune responses in a subject, see, e.g., the method of Rowe et al, 1973. Virus neutralization titers can be quantified in a number of ways, including: lysis plaques were counted after crystal violet fixation/staining of the cells (plaque assay); microscopic observation of cell lysis in vitro culture; and 2) ELISA and spectrophotometric detection of coronaviruses.

As used herein, the term "epitope" or "epitopes" refers to the structural portion of an antigen to which an antibody specifically binds.

Methods of producing antibodies or antibody fragments are provided, the methods comprising administering a modified viral structural protein, trimer or a modified viral structural protein of a trimer or a VLP comprising a modified viral structural protein as described herein to a subject, or host animal, thereby producing antibodies or antibody fragments. Antibodies or antibody fragments produced by the methods are also provided.

Thus, the present disclosure also provides for the use of a viral structural protein or VLP comprising a modified viral structural protein as described herein for inducing immunity to a coronavirus infection in a subject. Also disclosed herein are antibodies or antibody fragments prepared by administering a modified viral structural protein or VLP comprising the modified viral structural protein to a subject or host animal.

Also provided are compositions comprising an effective dose of a modified viral structural protein as described herein or a VLP comprising the modified viral structural protein, and a pharmaceutically useful carrier, adjuvant, vehicle or excipient for inducing an immune response in a subject. Also provided are vaccines for inducing an immune response to a coronavirus in a subject, wherein the vaccine comprises an effective dose of a modified viral structural protein or VLPs comprising the modified viral structural protein.

Also provided are compositions, which may include a mixture of VLPs, provided that at least one VLP within the composition comprises a modified coronavirus S protein as described herein. For example, each coronavirus S protein from each of one or more coronavirus families, subgroups, types, subtypes, lineages or strains comprising one or more than one modified S protein may be expressed and the corresponding VLP purified. Virus-like particles obtained from two or more than two coronavirus families, subgroups, types, subtypes, lineages or strains (e.g., two, three, four, five, six, seven, eight, nine, ten or more coronavirus families, subgroups, types, subtypes, lineages or strains) can be combined as desired to produce a mixture of VLPs, so long as one or more of the mixture of VLPs comprises a modified S protein as described herein. VLPs may be combined or produced in a desired ratio, e.g., in about comparable proportions, or in a manner such that one coronavirus family, subgroup, type, subtype, lineage or strain comprises a majority of VLPs in the composition. Also provided are compositions of VLPs comprising one or more modified S proteins having an extracellular domain and/or a TM or portion of a TM derived from each of one or more than one coronavirus family, subgroup, type, subtype, lineage or strain, whereby a mixture of different modified S proteins as provided in the present disclosure may be present in any individual VLP of the composition.

The composition or vaccine may comprise VLPs comprising modified viral structural proteins, such as modified S proteins from one type of coronavirus family, subgroup, type, subtype, lineage or strain, or the composition or vaccine may comprise multiple VLP types, wherein each VLP type comprises a modified S protein, wherein the modified S proteins in the same VLP are derived from one type of coronavirus family, subgroup, type, subtype, lineage or strain, i.e. the composition or vaccine may comprise a mixture of different coronavirus VLPs, wherein each may comprise modified S proteins from the same coronavirus family, subgroup, type, subtype, lineage or strain. For example, the composition or vaccine may include a first VLP comprising a first modified S protein from a first coronavirus family, subgroup, type, subtype, lineage, or strain, and a second VLP comprising a second modified S protein from a second coronavirus family, subgroup, type, subtype, lineage, or strain. In addition, the composition may further comprise a third VLP comprising a third modified S protein from a third coronavirus family, subgroup, type, subtype, lineage or strain, and/or the composition or vaccine may comprise a fourth VLP comprising a fourth modified S protein from a fourth coronavirus family, subgroup, type, subtype, lineage or strain. Thus, the present description also provides monovalent (monovalent) or multivalent (multivalent) compositions or vaccines. The monovalent composition or vaccine may immunize a subject against a single type of coronavirus strain, while the multivalent composition or vaccine may immunize a subject against more than one coronavirus strain. For example, the composition or vaccine may be a bivalent composition or vaccine that upon administration can immunize a subject against two different types of coronavirus families, subgroups, types, subtypes, lineages, or strains. Furthermore, the composition or vaccine may be a trivalent composition, or the vaccine or composition may be a tetravalent or tetravalent composition or vaccine.

In addition, the multivalent composition may comprise VLPs comprising one or more than one modified S protein with different HA cytoplasmic tails. For example, the multivalent composition can comprise a VLP or a VLP comprising two or more modified S proteins, each comprising an S protein extracellular domain, an S protein transmembrane domain, and a cytoplasmic tail derived from HA of influenza H1, H3, H5, H6, H7, H9, or B strain. Non-limiting examples of influenza strains are, for example, H1California/7/2009, H3A/Minnesota/41/2019, H5A/Indonesia/5/05, H6A/Teal/Hong Kong/W312/97, H7A/Guangdong/17 SF003/2016, H9A/Hong Kong/1073/99 or B/Washington/02/2019.

Multivalent compositions or vaccines having multiple types of VLPs may also include pharmaceutically acceptable carriers, adjuvants, vehicles, or excipients for eliciting an immune response in a subject.

Adjuvant systems for enhancing the immune response of a subject to a vaccine antigen are well known and may be used in combination with a vaccine or pharmaceutical composition as described herein. Various types of adjuvants may be used. Common adjuvants for human use are aluminum hydroxide, aluminum phosphate and calcium phosphate. There are also some adjuvants based on oil emulsions (oil-in-water or water-in-oil emulsions, such as Freund's Incomplete Adjuvant (FIA), montanide ^TM Adjuvant 65 and Lipovant ^TM ) Products from bacteria (or synthetic derivatives thereof), endotoxins, fatty acids, paraffin oils or vegetable oils, cholesterol and fatty amines or natural organic compounds such as, for example, squalene. Non-limiting adjuvants that may be used include, for example, an oil-in-water emulsion of squalene oil (e.g., MF-59 or AS 03), an adjuvant consisting of synthetic TLR4 agonist Glucopyranosyl Lipid A (GLA) incorporated into a Stable Emulsion (SE) (GLA-SE), or CpG 1018 (toll-like receptor (TLR 9) agonist adjuvant).

Thus, a vaccine or pharmaceutical composition may include one or more than one adjuvant. For example, the vaccine or pharmaceutical composition may comprise aluminium hydroxide, aluminium phosphate, calcium phosphate, an oil-in-water or water-in-oil emulsion, an emulsion comprising squalene (e.g. MF-59 or AS 03), an emulsion comprising GLA-SE, or a CpG 1018 adjuvant.

The pharmaceutical compositions, vaccines or formulations in the present description may be prepared in a manner known per se, for example by conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tabletting processes.

The pharmaceutical composition, vaccine or formulation may be produced by mixing or premixing any of the constituent components prior to administration, for example, by manually or mechanically assisted mixing of two or more vaccine suspensions, pharmaceutically acceptable carriers, adjuvants, vehicles or excipients, as a step carried out prior to administration of the final formulation, vaccine or pharmaceutical composition.

The pharmaceutical composition, vaccine or formulation may be administered to a subject orally, intradermally, intranasally, intramuscularly, intraperitoneally, intravenously or subcutaneously.

The injection may be prepared in conventional form as a liquid solution or suspension, as a solid form suitable for solution or suspension in a liquid prior to injection, or as an emulsion. Suitable excipients are, for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, sodium glutamate, cysteine hydrochloride and the like. In addition, the injectable pharmaceutical composition may contain small amounts of non-toxic auxiliary substances, such as wetting agents, pH buffers, etc., if desired. Physiologically compatible buffers include, but are not limited to, hank's solution, ringer's solution, or physiological saline buffer. Absorption enhancing agents (e.g., liposomes) may be used if desired.

The composition or vaccine may be administered to the subject at one time (single dose). Furthermore, the vaccine or composition may be administered to the subject multiple times (multiple doses). Thus, the composition, formulation or vaccine may be administered to the subject in a single dose to elicit an immune response, or the composition, formulation or vaccine may be administered multiple times (multiple doses). For example, a dose of the composition or vaccine may be administered 2, 3, 4, or 5 times. Thus, the composition or vaccine may be administered to the subject in an initial dose, followed by one or more doses. The administration of the doses may be separated in time from each other. For example, after administration of an initial dose, one or more subsequent doses may be administered at 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, or from any time between administration of initial doses. Furthermore, the composition or vaccine may be administered once a year. For example, the composition or vaccine may be administered as a seasonal vaccine.

The present disclosure also provides the following sequences.

Table 4: SEQ ID NO and sequence illustration

The invention will be further illustrated in the following examples.

Examples

Example 1: modified structural proteinsPreparation of the constructs

SARS-CoV-2S protein constructs are produced using techniques well known in the art. For example, SARS-COV-2 spike protein with wtTMCT (construct numbers 8586, 8589, 8591, see FIGS. 8A-8C) was cloned as described below. Constructs of SARS-COV-2 spike protein with H5iTMCT (construct numbers 8592, 8595, 8597, see FIGS. 9A-9C) and constructs of SARS-COV-2 spike protein with H5iCT (construct numbers 8610, 8611, 8671, see FIGS. 10A-10C) were obtained using similar techniques and sequence primers, templates and products are described in Table 5.

SARS-COV-2 spike protein with wtTMCT (construct No. 8586, 8589, 8591)

The sequence encoding the mature SARS-CoV-2 spike (S) protein 2 (SEQ ID NO: 23) (with GSAS+K971P+V972P extracellular domain mutation and natural transmembrane domain and natural cytoplasmic tail (wtTMCT) from SARS-CoV-2, fused to alfalfa PDI secretion signal peptide (PDISP)) was cloned into three different expression systems using the following PCR-based method. Fragments containing the coding sequence of SARS-COV-2 spike protein (wtTMCT) were amplified using primers IF (PDI) -CoV (opt 2). C (SEQ ID NO: 24) and IF (AVB) -CoV (opt 2). R (SEQ ID NO: 25) using PDISP-SARS-COV-2 spike protein having wtTMCT gene sequence (SEQ ID NO: 22) as template. The PCR products were cloned into three different expression systems using an In-Fusion cloning system (Clontech, mountain View, calif.).

For the first expression system, construct number 8501 (fig. 7A) was hydrolyzed with aatlii and StuI restriction enzymes, and linearized plastids were used for the first In-Fusion assembly reaction. Construct number 8501 is a acceptor plastid intended for "In-Fusion" cloning of the gene of interest In a 2X35S (+C)/nbMT 78/PDI/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:31 provides the left to right sequence t-DNA border. The resulting construct is given a number 8586 (SEQ ID NO: 32). In SEQ ID NO:23 provides the amino acid sequence of the mature spike protein from SARS-COV-2 fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 8A shows an illustration of a plastid 8586.

For the second expression system, construct number 8500 was also hydrolyzed with AatII and StuI restriction enzymes (fig. 7B), and the linearized plasmid was used for the second In-Fusion assembly reaction. Construct number 8500 is a receptor plastid intended for "In-Fusion" cloning of a gene of interest In a 2X35S (+c)/nbCSY 65/PDI/AvB/NOS-based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:33 provides the left to right sequence t-DNA border. The resulting construct is given a number 8589 (SEQ ID NO: 34). In SEQ ID NO:23 provides the amino acid sequence of the mature spike protein from SARS-COV-2 fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 8B shows an illustration of a plastid 8589.

Construct number 8716 (fig. 7C) was also hydrolyzed with aatlii and StuI restriction enzymes for the third expression system, and the linearized plasmid was used for the third In-Fusion assembly reaction. Construct number 8716 is a receptor plastid intended for "In Fusion" cloning of a gene of interest In a 2X35S (+C)/nbHEL 40/PDI/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:33 provides the left to right sequence t-DNA border. The resulting construct was given the number 8591 (SEQ ID NO: 36). In SEQ ID NO:23 provides the amino acid sequence of the mature spike protein from SARS-COV-2 fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 8C shows a graphical representation of a plastid 8591.

SARS-CoV-2 spike protein with H5iTMCT (construct No. 8592, 8595, 8597)

The sequence encoding the mature spike (S) protein from SARS-CoV-2 with GSAS+K971P+V972P extracellular domain mutation and with transmembrane domain and cytoplasmic tail (H5 iTMCT) from H5A/Indonesia/5/05HA (SEQ ID NO: 27) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same three expression systems described above by a similar PCR-based method (primer see Table 5, for sequence used see example 3). Using techniques similar to those described above, construct No. 8592 (fig. 9A) was derived from receptor construct 8501, construct No. 8595 (fig. 9B) was derived from receptor construct 8500, and construct No. 8597 (fig. 9C) was derived from receptor construct 8716, and primers, templates, and products are provided in table 5 below. SARS-COV-2 spike protein with H5iCT (construct No. 8610, 8611, 8671)

The sequence encoding the mature spike (S) protein from SARS-CoV-2 with GSAS+K971P+V972P extracellular domain mutation and cytoplasmic tail (H5 iCT) from H5A/Indonesia/5/05HA (SEQ ID NO: 30) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same three expression systems described above by a similar PCR-based method (see Table 5 for primers, see example 3 for sequences used). Using techniques similar to those described above, construct No. 8610 (fig. 10A) was derived from receptor construct 8501, construct No. 8611 (fig. 10B) was derived from receptor construct 8500, and construct No. 8671 (fig. 10C) was derived from receptor construct 8716, and primers, templates, and products are provided in table 5 below.

SARS-COV-2 spike protein with alternative TM CT fusion sequence (construct No. 8980, 8981, 8982, 8983)

The sequence encoding the mature spike (S) protein from SARS-CoV-2 with GSAS+K971P+V972P extracellular domain mutation and cytoplasmic tail (H5 iCT) from H5A/Indonesia/5/05HA (SEQ ID NO: 19) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described for construct 8671, resulting in construct 8980 (FIG. 12A). For the sequences encoding the mature spike (S) protein from SARS-CoV-2 with GSAS+K971P+V972P extracellular domain mutation and cytoplasmic tail (H5 iCT) from H5A/Indonesia/5/05HA, a similar construct was generated as shown in SEQ ID NO:37 (construct 8981, fig. 12B), SEQ ID NO:38 (construct 8982, fig. 12C) and SEQ ID NO:39 (construct 8983, FIG. 12D).

SARS-COV-2 spike protein with CT from other HA strains (construct No. 7390, 7391, 7392, 7393, 7394 and 7395)

Sequences encoding the mature spike (S) protein from SARS-CoV-2 with gsas+k971p+v972p extracellular domain mutation and cytoplasmic tail (H1 CT) from H1A/California/7/2009HA were fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described above for construct 8671 by a similar PCR-based method (see table 5 for primers and for sequences used see example 3). The resulting construct 7390 thus encodes a modified S protein comprising the cytoplasmic tail of H1A/California/7/2009HA (H1 CT) (fig. 13A). Similar constructs were produced for H3A/Minnesota/41/2019 (construct 7391, H3 CT) (FIG. 13B), H6A/Teal/Hong Kong/W312/97 (construct 7392, H6 CT) (FIG. 13C), H7A/Guangdong/17SF003/2016 (construct 7393, H7 CT) (FIG. 13D), H9A/Hong Kong/1073/99 (construct 7394, H9H CT) (FIG. 13E), or B/Washington/02/2019 (construct 7395, HA B CT) (FIG. 13F).

SARS-COV-2 spike protein with substitution (construct No. 8933, 8960, 8947)

Modified SARS-CoV-2S protein constructs comprising mutations in the S protein, such as the combination of R667G, R668S, R670S, F802P, A877P, A884P, A927P, K971P, V972P and L923F, were produced using techniques well known in the art and as essentially described above. The construct had the following substitutions: construct 8933: R667G, R668S, R670S, K971P, V972P and L923F ("GSAS-2P-923"); construct 8960: R667G, R668S, R670S, F802P, A927P, K971P, V972P and L923F ("GSAS-4P-923") and construct 8947: R667G, R668S, R670S, F802P, A877P, A884P, A927P, K971P, V972P and L923F ("GSAS-6P-923").

SARS-COV-1 spike protein with wtTMCT and modified TMCT (construct No. 9231, 9232, 9233, 9234, 9235)

The sequence encoding the mature SARS-CoV-1 spike (S) protein having the R650A+K955P+V956P extracellular domain mutation and having the native transmembrane domain and the native cytoplasmic tail (wtTMCT) from SARS-CoV-1 (SEQ ID NO: 88) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the following expression system by a PCR-based method. The fragment containing the coding sequence of PDISP-SARS-COV-1 spike protein (wtTMCT) was amplified using primers IF (nbHEL 40) -PDI.c (SEQ ID NO: 86) and IF (AvB +wtCT). R (SEQ ID NO: 87) using PDISP-SARS-COV-1 spike protein having wtTMCT gene sequence (SEQ ID NO: 88) as template. The PCR product was cloned into the following expression system using an In-Fusion cloning system (Clontech, mountain View, calif.).

Construct No. 7147 (fig. 21) was digested with aatlii and StuI restriction enzymes and the linearized plasmid was used for the first In-Fusion assembly reaction. Construct No. 7147 is a receptor plastid intended for "In-Fusion" cloning of a gene of interest In a 2X35S (+C)/nbHEL 40/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:111 provides the left to right sequence t-DNA border. The resulting construct is given the number 9231. In SEQ ID NO:93 provides the amino acid sequence of the mature spike protein from SARS-COV-1 fused to alfalfa PDI secretion signal peptide (PDISP). Figure 18A shows a schematic representation of a plastid 9231.

Sequences encoding the mature spike (S) protein from SARS-CoV-1 with the r7a+k955p+v956p extracellular domain mutation and i) the transmembrane domain and cytoplasmic tail from H5A/Indonesia/5/05HA (H5 ittct), ii) cytoplasmic tail from H5A/Indonesia/5/05HA (H5 iCT and variant H5iCT (V4)), or iii) cytoplasmic tail from H1A/California/7/2009 HA (H1 cCT) were fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described above for construct 9231 by a similar PCR-based method (primer see table 5 and sequence used see example 3). The resulting constructs 9232, 9233, 9234, 9235 thus encoded a modified S protein comprising H5A/Indonesia/5/05 TMCT (H5 iTMCT) (FIG. 18B, SEQ ID NO: 94), a modified SARS-COV-1S protein comprising H5A/Indonesia/5/05 CT (H5 iCT) (FIG. 18C, SEQ ID NO: 95), a modified S protein comprising H5A/Indonesia/5/05 CT variant (H5 iCT (V4)) (FIG. 18D, SEQ ID NO: 96) or a modified S protein comprising H1A/California/7/2009 CT (H1 cCT) (FIG. 18E, SEQ ID NO: 97).

MERS-CoV spike protein with wtTMCT and modified TMCT (construct numbers 9246, 9247, 9249, 9250, 9251)

The sequence encoding the mature MERS-CoV spike (S) protein with the r730a+r733g+v1043p+l1044p extracellular domain mutation and with the natural transmembrane domain and natural cytoplasmic tail (wtTMCT) from MERS-CoV (SEQ ID NO: 101) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the following expression system by a PCR-based method. Fragments containing the PDISP-MERS-COV spike protein (wtTMCT) coding sequence were amplified using primers IF (nbHEL 40) -PDI.c (SEQ ID NO: 86) and IF (AvB +wtCT-MERS). R (SEQ ID NO: 98) using PDISP-MERS-COV spike protein having wtTMCT gene sequence (SEQ ID NO: 101) as template. The PCR product was cloned into the following expression system using an In-Fusion cloning system (Clontech, mountain View, calif.).

Construct No. 7147 (fig. 21) was digested with aatlii and StuI restriction enzymes and the linearized plasmid was used for the first In-Fusion assembly reaction. Construct No. 7147 is a receptor plastid intended for "In-Fusion" cloning of a gene of interest In a 2X35S (+C)/nbHEL 40/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:111 provides the left to right sequence t-DNA border. The resulting construct was given the number 9246. In SEQ ID NO:106 provides the amino acid sequence of the mature spike protein from MERS-COV fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 20A shows a schematic representation of a plastid 9246.

The sequences encoding the mature spike (S) proteins from MERS-CoV with the R730a+r733g+v1043p+l1044p extracellular domain mutations and i) the transmembrane domain and cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 ittct), ii) cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 iCT and variant H5iCT (V4)), or iii) cytoplasmic tail from H1A/California/7/2009 HA (H1 cCT) were fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described above for construct 9246 by a PCR-based approach (see table 5 for primers and sequences used see example 3). The resulting constructs 9247, 9249, 9250, 9251 thus encoded a modified MERS-COV protein comprising H5A/Indonesia/5/05 TMCT (H5 ittct) (fig. 20B,SEQ ID NO:107), a modified S protein comprising H5A/Indonesia/5/05 CT (H5 iCT) (fig. 20C,SEQ ID NO:108), a modified S protein comprising a H5A/Indonesia/5/05 CT variant (H5 iCT (V4)) or a modified S protein comprising H1A/California/7/2009 CT (H1 cCT) (fig. 20E,SEQ ID NO:110).

OC43-CoV spike protein with wtTMCT and modified TMCT (construct No. 9269, 9270, 9272, 9273 and 9274)

The sequence (SEQ ID NO: 137) encoding the mature OC43-CoV spike (S) protein with the R761G+R762G+R764G+R765S+A1077P+L1078P extracellular domain mutation and with the native transmembrane domain and the native cytoplasmic tail (wtTMCT) from OC43-CoV was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the following expression system by a PCR-based method. Fragments containing the coding sequence of PDISP-OC43-COV spike protein (wtTMCT) were amplified using primers IF (nbHEL 40) -PDI.c (SEQ ID NO: 86) and IF (AvB +wtCT-OC 43). R (SEQ ID NO: 136) using PDISP-OC43-COV spike protein having wtTMCT gene sequence (SEQ ID NO: 137) as template. The PCR product was cloned into the following expression system using an In-Fusion cloning system (Clontech, mountain View, calif.).

Construct No. 7147 (fig. 21) was digested with aatlii and StuI restriction enzymes and the linearized plasmid was used for the first In-Fusion assembly reaction. Construct No. 7147 is a receptor plastid intended for "In-Fusion" cloning of a gene of interest In a 2X35S (+C)/nbHEL 40/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:111 provides the left to right sequence t-DNA border. The resulting construct was assigned number 9269. In SEQ ID NO:142 provides the amino acid sequence of the mature spike protein from OC43-COV fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 24A shows a graphical representation of plastid 9269.

The sequences encoding the mature spike (S) proteins from OC43-CoV with the extracellular domain of r761g+r762 g+r765s+a1077p+l1078p and i) the transmembrane domain and cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 ittct), ii) cytoplasmic tail from H5A/Indonesia/5/05 HA (H5 iCT and variant H5iCT (V4)), or iii) cytoplasmic tail from H1A/California/7/2009 HA (H1 cCT) were fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described above for construct 9269 by a similar PCR-based method (primer see table 5 and for sequences used see example 3). The resulting constructs 9270, 9272, 9273 and 9274 thus encoded a modified OC43-COV protein comprising H5A/Indonesia/5/05 TMCT (H5 ittct) (fig. 24B,SEQ ID NO:143), a modified S protein comprising H5A/Indonesia/5/05 CT (H5 iCT) (fig. 24C,SEQ ID NO:144), a modified S protein comprising a H5A/Indonesia/5/05 CT variant (H5 iCT (V4)) or a modified S protein comprising H1A/California/7/2009 CT (H1 cCT) (fig. 24E,SEQ ID NO:146).

229E-CoV spike protein with wtTMCT and modified TMCT (construct numbers 9310, 9311, 9312, 9313 and 9314)

The sequence encoding the mature 229E-CoV spike (S) protein with the R567A+T871P+I872P extracellular domain mutation and with the native transmembrane domain from 229E-CoV and the native cytoplasmic tail (wtTMCT) (SEQ ID NO: 148) was fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the following expression system by a PCR-based method. Fragments containing the coding sequence of PDISP-229E-COV spike protein (wtTMCT) were amplified using primers IF (nbHEL 40) -PDI.c (SEQ ID NO: 86) and IF (CoV 229 EwtCT). R (SEQ ID NO: 147) using PDISP-OC43-COV spike protein with wtTMCT gene sequence (SEQ ID NO: 148) as template. The PCR product was cloned into the following expression system using an In-Fusion cloning system (Clontech, mountain View, calif.).

Construct No. 7147 (fig. 21) was digested with aatlii and StuI restriction enzymes and the linearized plasmid was used for the first In-Fusion assembly reaction. Construct No. 7147 is a receptor plastid intended for "In-Fusion" cloning of a gene of interest In a 2X35S (+C)/nbHEL 40/AvB/NOS based expression cassette. The receptor plasmid also incorporates a gene construct for co-expression of the silenced TBSV P19 inhibitor gene under the alfalfa plastocyanin gene promoter and terminator. The backbone is pCAMBIA binary plasmid and in SEQ ID NO:111 provides the left to right sequence t-DNA border. The resulting construct is given a number 9310. In SEQ ID NO:153 provides the amino acid sequence of the mature spike protein from 229E-COV fused to alfalfa PDI secretion signal peptide (PDISP). Fig. 26A shows a graphical representation of a plastid 9310.

The sequences encoding mature spike (S) proteins from 229E-CoV with the r567a+t871p+i872p extracellular domain mutation and I) transmembrane domain and cytoplasmic tail from H5A/Indonesia/5/05HA (H5 ittct), ii) cytoplasmic tail from H5A/Indonesia/5/05HA (H5 iCT and variant H5iCT (V4)), or iii) cytoplasmic tail from H1A/California/7/2009 HA (H1 cCT) were fused to alfalfa PDI secretion signal peptide (PDISP) and cloned into the same expression system as described above for construct 9310 by a similar PCR-based method (primer see table 5 and sequence used see example 3). The resulting constructs 9311, 9312, 9313 and 9314 thus encode a modified 229E-COV protein comprising H5A/Indonesia/5/05 TMCT (H5 ittct) (fig. 26B,SEQ ID NO:154), a modified S protein comprising H5A/Indonesia/5/05CT (H5 iCT) (fig. 26C,SEQ ID NO:155), a modified S protein comprising a H5A/Indonesia/5/05CT variant (H5 iCT (V4)) (fig. 26D,SEQ ID NO:156), or a modified S protein comprising H1A/California/7/2009 CT (H1 cCT) (fig. 26E,SEQ ID NO:157).

Example 2: method of

Agrobacterium (Agrobacterium tumefaciens) transfection

Agrobacterium strain (Agrobacterium tumefaciens) AGL1 was transfected with a SARS-CoV-2 modified S protein expression vector by electroporation using the method described by D' Aoust et al, 2008 (Plant Biotech. J. 6:930-40). Transfected Agrobacterium was grown to OD in YEB medium supplemented with 10mM2- (N-morpholinyl) ethanesulfonic acid (MES), 20. Mu.M acetosyringone, 50. Mu.g/ml kanamycin and 25. Mu.g/ml carbenicillin pH 5.6 ₆₀₀ Between 0.6 and 16. Agrobacterium suspension was centrifuged before use and resuspended in infiltration medium (10 mM MgCl) ₂ And 10mM MES pH 5.6).

Preparation of plant biomass, inoculation and agroinfiltration

The present Sambucus sambac (N.benthamiana) plants were grown from seeds in plain land filled with commercial peat moss substrates. Plants were grown in a greenhouse under 16/8 photoperiod and 25℃day/20℃night temperature conditions. 3 weeks after sowing, individual plantlets were picked, transplanted into pots and grown in a greenhouse for another three weeks under the same environmental conditions.

Agrobacterium transfected with each expression vector was grown in YEB medium supplemented with 10mM 2- (N-morpholinyl) ethanesulfonic acid (MES), 20. Mu.M acetosyringone, 50. Mu.g/ml kanamycin and 25. Mu.g/ml carbenicillin pH 5.6 until they reached OD ₆₀₀ Between 0.6 and 16. Agrobacterium suspension was centrifuged before use and resuspended in infiltration medium (10 mM MgCl) ₂ And 10mM MES pH 5.6) and stored overnight at 4 ℃. On the day of infiltration, the culture batch was grownDiluted at 2.5 culture volumes and warmed prior to use. Whole plants of nicotiana benthamiana (n.benthamiana) were inverted in bacterial suspension in an airtight stainless steel tank under vacuum of 20-40 torr for 2 minutes. Plants were returned to the greenhouse for a 6 or 9 day incubation period until harvest.

Leaf harvest and total protein and VLP extraction

After cultivation, the aerial parts of the plants were harvested, frozen at-80℃and crushed. Total soluble proteins were extracted by mechanical homogenization (Polytron) of each frozen crushed plant material sample in 2 volumes of cold 50mM Tris buffer (pH 8.0+500mM NaCl,0.4. Mu.g/ml metabisulfite and 1mM phenylmethanesulfonyl fluoride). After homogenization, the slurry was centrifuged at 10,000g for 10 min at 4 ℃ and these clear crude extracts (supernatants) were retained for analysis.

The total protein content of the clarified crude extract was determined by Bradford assay (Bio-Rad, hercules, california) using bovine serum albumin as a reference standard. Under reducing conditions, criterion is used ^TM TGX Stain-Free ^TM The pre-gels (Bio-Rad Laboratories, hercules, calif.) were used to isolate proteins by SDS-PAGE. Proteins were visualized by staining the gel with coomassie brilliant blue. Alternatively, use Gel Doc ^TM EZ imaging System (Bio-Rad Laboratories, hercules, calif.) visualizes proteins and electrotransfers them to polyvinylidene difluoride (PVDF) membranes (Roche Diagnostics Corporation, indianapolis, indianana) for immunodetection. Prior to immunoblotting, the membranes were blocked with 5% nonfat milk powder and 0.1% tween-20 in Tris-buffered saline (TBS-T) at 4 ℃ for 16-18h.

For VLP purification, proteins were extracted from frozen biomass by mechanical extraction using a mixer with two volumes of extraction buffer (50 mM Tris buffer, pH 7.0+500mM NaCl) and the pH was lowered to 6.1 using 0.5M citric acid. The slurry was filtered through a macroporous nylon filter to remove large debris and centrifuged at 5000g for 5 minutes at 4 ℃. The supernatant was collected and centrifuged again at 5000g for 30 minutes (4 ℃) to remove additional debris and passed through a clarification filter. The supernatant was then loaded onto a discontinuous iodixanol density gradient. Analytical density gradient centrifugation was performed as follows: a38 mL tube (3 mL 35%, 3mL 30%, 3mL 25%, 3mL 15% and 5mL 10% iodixanol) containing a discontinuous iodixanol density gradient in Tris buffer was prepared and covered with 22 mL of extract containing virus-like particles. The gradient was centrifuged at 120,000g for 2 hours (4 ℃ C.). After centrifugation, 1mL fractions were collected from bottom to top and analyzed by SDS-PAGE binding protein staining or immunoblotting. Fractions 6 to 9 were pooled and buffer exchanged using an Amicon centrifuge device. Protein content was determined by Bradford assay.

Protein analysis and immunoblotting

Immunoblots were performed by first incubation with a first mAb (anti-S1, sino Biological, catalog No. 40150-R007 or anti-S2, novus Biological, catalog No. NB 100-56578) diluted in 2% nonfat milk in TBS-Tween 20.1%. Peroxidase conjugated goat anti-rabbit (Jackson Immunoresearch, cat# 115-035-144) was used as a secondary antibody for chemiluminescent detection in 2% nonfat milk powder in TBS-Tween 20.1%. Immunoreactive complexes were detected by chemiluminescence using luminol as substrate (Roche Diagnostics Corporation). By using EZ-LinkThe activated peroxidase-conjugated kit (Pierce, rockford, ill.) performs horseradish peroxidase-enzyme conjugation of human IgG antibodies.

In plants, the clear crude extract was evaluated for yield and analyzed using capillary-based electrophoresis (biotechnology) technology and WES analysis system. Briefly, soluble proteins from the crude extract are separated by molecular weight in capillaries and immobilized to a substrate. Standard curves using purified VLPs were used to determine the amount of S protein and tested using anti-S2 antibodies (Novus bio, cat. No. NB 100-56578) according to the manufacturer' S instructions. The yields were then normalized using the control construct set to 1.

The first antibody used for detection of SARS-CoV S protein was SARS-CoV spike S1 subunit antibody from Sino Biologicals, 40150-MM08 (1/5000), and the second antibody used for detection was goat anti-mouse, JIR,115-035-146 (1/10000). The primary antibody used to detect MERS CoV S protein is MERS-CoV spike protein S1 antibody (N-terminal) from the Sino Biological (100208-RP 02, 1/5000). The second antibody used for detection was a goat anti-mouse antibody from JIR (115-035-144,1/10000). The primary antibody used for detection was anti-coronavirus OC43 spike protein from Antibodies-online (ABIN 2754654, 1/1000). The second antibody used for detection was a goat anti-rabbit antibody from JIR (111-035-144,1/10000).

Electron microscope

To determine whether the expressed S protein assembled into VLPs, the purified VLPs were subjected to Transmission Electron Microscopy (TEM) to immunocapture particles. A glow discharge carbon/copper grid (10 s,0.3 mbar) was placed on 20 μl of purified VLP (100 μg/mL) for 5 minutes, then washed 4 times with sterile distilled water. The grid was floated on 20 μl of 2% uranyl acetate for 1 min, then excess solution was removed by contacting wet filter paper and allowed to dry on filter paper for 24 hours, then observed under TEM (Tecnai Microscope).

Example 3: sequence(s)

The following sequences were used in the above-described embodiments.

Natural SARS-CoV-2S protein wtTM/CT AA (P0 DTC 2) (SEQ ID NO: 1) MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

Natural SARS-CoV-2S protein wtTM/CT AA (P0 DTC 2), NO Signal Peptide (SP) (SEQ ID NO: 2)

VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPIN

LVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAG

AAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVE

KGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRIS

NCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVR

QIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLF

RKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGY

QPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLT

ESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNT

SNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIG

AEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAE

NSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLL

LQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNF

SQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQ

KFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQM

AYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDV

VNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRL

QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHL

MSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVS

NGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELD

SFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES

LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLK

GCCSCGSCCKFDEDDSEPVLKGVKLHYT

H5 A/Indonesia/5/05 Hemagglutinin (HA) AA (A5A 5L 7) (SEQ ID NO: 3)

MEKIVLLLAIVSLVKSDQICIGYHANNSTEQVDTIMEKNVTVTHAQDILE

KTHNGKLCDLDGVKPLILRDCSVAGWLLGNPMCDEFINVPEWSYIVEK

ANPTNDLCYPGSFNDYEELKHLLSRINHFEKIQIIPKSSWSDHEASSGVSS

ACPYLGSPSFFRNVVWLIKKNSTYPTIKKSYNNTNQEDLLVLWGIHHPN

DAAEQTRLYQNPTTYISIGTSTLNQRLVPKIATRSKVNGQSGRMEFFWTI

LKPNDAINFESNGNFIAPEYAYKIVKKGDSAIMKSELEYGNCNTKCQTP

MGAINSSMPFHNIHPLTIGECPKYVKSNRLVLATGLRNSPQRESRRKKR

GLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKESTQKAIDG

VTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKKMEDGFLDVWTYN

AELLVLMENERTLDFHDSNVKNLYDKVRLQLRDNAKELGNGCFEFYH

KCDNECMESIRNGTYNYPQYSEEARLKREEISGVKLESIGTYQILSIYST

VASSLALAIMMAGLSLWMCSNGSLQCRICI

H5 A/Indonesia/5/05 Hemagglutinin (HA) Virus cDNA (EF 541394.1) (SEQ ID NO: 4)

CTGTAAAAATGGAGAAAATAGTGCTTCTTCTTGCAATAGTCAGTCTT

GTTAAAAGTGATCAGATTTGCATTGGTTACCATGCAAACAATTCAAC

AGAGCAGGTTGACACAATCATGGAAAAGAACGTTACTGTTACACAT

GCCCAAGACATACTGGAAAAGACACACAACGGGAAGCTCTGCGATC

TAGATGGAGTGAAGCCTCTAATTTTAAGAGATTGTAGTGTAGCTGGA

TGGCTCCTCGGGAACCCAATGTGTGACGAATTCATCAATGTACCGGA

ATGGTCTTACATAGTGGAGAAGGCCAATCCAACCAATGACCTCTGTT

ACCCAGGGAGTTTCAACGACTATGAAGAACTGAAACACCTATTGAG

CAGAATAAACCATTTTGAGAAAATTCAAATCATCCCCAAAAGTTCTT

GGTCCGATCATGAAGCCTCATCAGGAGTGAGCTCAGCATGTCCATAC

CTGGGAAGTCCCTCCTTTTTTAGAAATGTGGTATGGCTTATCAAAAA

GAACAGTACATACCCAACAATAAAGAAAAGCTACAATAATACCAAC

CAAGAAGATCTTTTGGTACTGTGGGGAATTCACCATCCTAATGATGC

GGCAGAGCAGACAAGGCTATATCAAAACCCAACCACCTATATTTCC

ATTGGGACATCAACACTAAACCAGAGATTGGTACCAAAAATAGCTA

CTAGATCCAAAGTAAACGGGCAAAGTGGAAGGATGGAGTTCTTCTG

GACAATTTTAAAACCTAATGATGCAATCAACTTCGAGAGTAATGGA

AATTTCATTGCTCCAGAATATGCATACAAAATTGTCAAGAAAGGGG

ACTCAGCAATTATGAAAAGTGAATTGGAATATGGTAACTGCAACAC

CAAGTGTCAAACTCCAATGGGGGCGATAAACTCTAGTATGCCATTCC

ACAACATACACCCTCTCACCATCGGGGAATGCCCCAAATATGTGAAATCAAACAGATTAGTCCTTGCAACAGGGCTCAGAAATAGCCCTCAAAGAGAGAGCAGAAGAAAAAAGAGAGGACTATTTGGAGCTATAGCAGGTTTTATAGAGGGAGGATGGCAGGGAATGGTAGATGGTTGGTATGGGTACCACCATAGCAATGAGCAGGGGAGTGGGTACGCTGCAGACAAAGAATCCACTCAAAAGGCAATAGATGGAGTCACCAATAAGGTCAACTCAATCATTGACAAAATGAACACTCAGTTTGAGGCCGTTGGAAGGGAATTTAATAACTTAGAAAGGAGAATAGAGAATTTAAACAAGAAGATGGAAGACGGGTTTCTAGATGTCTGGACTTATAATGCCGAACTTCTGGTTCTCATGGAAAATGAGAGAACTCTAGACTTTCATGACTCAAATGTTAAGAACCTCTACGACAAGGTCCGACTACAGCTTAGGGATAATGCAAAGGAGCTGGGTAACGGTTGTTTCGAGTTCTATCACAAATGTGATAATGAATGTATGGAAAGTATAAGAAACGGAACGTACAACTATCCGCAGTATTCAGAAGAAGCAAGATTAAAAAGAGAGGAAATAAGTGGGGTAAAATTGGAATCAATAGGAACTTACCAAATACTGTCAATTTATTCAACAGTGGCGAGTTCCCTAGCACTGGCAATCATGATGGCTGGTCTATCTTTATGGATGTGCTCCAATGGATCGTTACAATGCAGAATTTGCATTTAAATTTGTGAGTTCAG

Modified SARS-CoV-2 with H5A/Indonesia/5/05 hemagglutinin CT AA (SEQ ID NO: 5)

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

H1 A/California/7/2009 hemagglutinin TM/CT AA (SEQ ID NO: 6)

IDGVKLESTRIYQILAIYSTVASSLVLVVSLGAISFWMCSNGSLQCRICIH 2A/Singapore/1/1957 hemagglutinin TM/CT AA (SEQ ID NO: 7)

IKGVKLSSMGVYQILAIYATVAGSLSLAIMMAGISFWMCSNGSLQCRICIH 3A/Minnesota/41/2019 hemagglutinin TM/CT AA (SEQ ID NO: 8)

IKGVELKSGYKDWILWISFAISCFLLCVALLGFIMWACQKGNIRCNICIH 5A/Indonesia/5/05 hemagglutinin TM/CT AA (SEQ ID NO: 9)

ISGVKLESIGTYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICIH 6A/Teal/Hong Kong/W312/97 hemagglutinin TM/CT AA (SEQ ID NO: 10)

IESVKLENLGVYQILAIYSTVSSSLVLVGLIMAMGLWMCSNGSMQCRICI

H7 A/Guangdong/17SF003/2016 hemagglutinin TM/CT AA (SEQ ID NO: 11)

IDPVKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

H9 A/Hong Kong/1073/99 hemagglutinin TM/CT AA (SEQ ID NO: 12)

IEGVGESEGTYKILTIYSTVASLASLVLAMGGFAAFLWAMSNGSCRCNICIB/Washington/02/2019 hemagglutinin TM/CT AA (SEQ ID NO: 13)

AASLNDDGLDNHTILLYYSTAASSLAVTLMIAIFVVYMVSRDNVSCSICL

Consensus sequence of the C-terminal region of influenza hemagglutinin (SEQ ID NO: 14)

Consensus sequence of CT domain of IXGVGKLXSXXXXILXYSTVASLXXXXXXXwmcssXXCXICI influenza hemagglutinin (SEQ ID NO: 15)

XXwmcsngsXXCXICI

The C-terminal region of the natural SARS-CoV-2S protein wtTM/CT (SEQ ID NO: 16)

WYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

H5 A/Indonesia/5/05 hemagglutinin C-terminal region (SEQ ID NO: 17)

ISGVKLESIGTYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

Modified SARS-CoV-2S protein C-terminal region with H5i hemagglutinin CT (SEQ ID NO: 18)

WYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

Modified SARS-CoV-2S protein C-terminal region with H5i hemagglutinin CT, variation 1 (SEQ ID NO: 19)

WYIWLGFIAGLIAIVMVTIMMAGLSLWMCSNGSLQCRICI

( SP-free) SARS-CoV-2S protein gsas+pp wtTM/CT AA (SEQ ID NO:20 )

VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVR

QIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLF

RKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGY

QPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLT

ESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNT

SNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIG

AEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAE

NSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLL

LQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNF

SQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQ

KFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQM

AYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDV

VNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRL

QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHL

MSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVS

NGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELD

SFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES

LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLK

GCCSCGSCCKFDEDDSEPVLKGVKLHYT

(no SP) modified SARS-CoV-2S protein GSAS+PP with H5i hemagglutinin

CT AA(SEQ ID NO：21)

VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTW

FHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKT

QSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSS

ANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPIN

LVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAG

AAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVE

KGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRIS

NCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVR

QIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLF

RKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGY

QPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLT

ESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNT

SNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIG

AEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAE

NSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLL

LQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNF

SQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQ

KFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQM

AYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDV

VNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRL

QSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHL

MSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVS

NGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELD

SFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNES

LIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQ

CRICI

PDI-SARS-CoV-2S protein GSAS+PP wtTM/CT-DNA (SEQ ID NO: 22)

ATGGCGAAAAACGTTGCGATTTTCGGCTTATTGTTTTCTCTTCTTGTG

TTGGTTCCTTCTCAGATCTTCGCGGTGAATCTTACGACGCGAACACA

GTTACCACCCGCATATACAAATAGCTTCACTCGGGGTGTTTATTACC

CCGACAAAGTGTTCAGGTCCTCCGTGCTCCACTCAACACAGGACCTC

TTTCTTCCTTTCTTTTCTAACGTGACATGGTTTCATGCCATTCATGTAT

CCGGCACTAACGGTACTAAGAGGTTCGATAATCCTGTGCTCCCTTTC

AATGACGGCGTTTACTTTGCAAGCACAGAGAAGAGTAACATCATCC

GAGGTTGGATCTTTGGCACTACCCTCGATTCAAAGACGCAGAGCCTC

CTCATTGTGAACAATGCCACTAACGTGGTGATCAAAGTTTGCGAGTT

TCAGTTCTGCAATGACCCTTTCTTGGGGGTGTACTATCATAAGAACA

ACAAGTCTTGGATGGAATCTGAATTCCGCGTCTATAGCAGCGCCAAC

AACTGCACCTTTGAATACGTGTCCCAGCCCTTCCTTATGGACCTGGA

GGGAAAGCAGGGAAACTTTAAGAATCTGAGAGAGTTCGTGTTTAAA

AATATCGACGGCTATTTTAAGATCTATTCTAAGCACACGCCTATTAA

TCTCGTGCGCGATCTTCCACAAGGCTTCAGCGCCCTGGAACCACTCG

TGGACCTCCCAATTGGTATCAACATCACTAGATTTCAGACTCTGCTT

GCCCTCCACCGATCCTATCTGACACCCGGAGACTCCTCTAGCGGCTG

GACTGCCGGCGCTGCCGCTTATTACGTTGGTTATCTTCAGCCACGCA

CGTTCCTGCTGAAGTATAACGAGAATGGTACTATTACCGATGCCGTG

GATTGTGCCCTTGACCCCCTGTCCGAAACTAAGTGCACACTCAAGTC

ATTCACTGTGGAAAAAGGAATCTACCAGACAAGCAATTTTCGGGTCC

AGCCTACTGAGAGCATTGTGCGCTTTCCTAACATCACAAATCTTTGC

CCCTTCGGAGAGGTTTTCAATGCTACACGGTTTGCCTCCGTGTATGC

CTGGAACCGCAAGAGAATTTCCAATTGCGTGGCCGATTACTCCGTGC

TCTACAATAGTGCAAGCTTTAGCACCTTTAAGTGCTATGGCGTATCC

CCTACTAAGCTTAACGACTTGTGTTTCACAAACGTGTATGCCGACTC

CTTTGTGATACGGGGCGACGAAGTTAGACAGATAGCACCAGGACAG

ACGGGAAAGATAGCTGACTACAACTATAAGCTTCCTGATGACTTCAC

TGGCTGCGTTATCGCGTGGAATTCTAACAACCTGGACTCAAAAGTCG

GCGGCAACTATAACTATCTCTATCGGCTGTTCCGCAAGAGTAACCTT

AAGCCCTTTGAGAGAGATATAAGCACTGAAATCTACCAGGCTGGCA

GTACGCCCTGTAATGGCGTGGAAGGCTTTAATTGTTATTTTCCACTG

CAATCCTATGGTTTTCAGCCAACCAATGGCGTGGGCTACCAACCATA

CCGCGTCGTGGTGCTCTCCTTTGAACTGCTCCACGCTCCCGCGACTGT

CTGCGGCCCCAAGAAGTCCACGAACCTTGTGAAGAATAAGTGCGTT

AATTTTAATTTCAACGGCCTCACTGGAACAGGAGTGCTCACTGAGAG

TAACAAGAAGTTCCTGCCATTTCAACAATTTGGCAGAGACATAGCCG

ATACTACTGACGCCGTTAGGGACCCCCAGACCCTCGAGATTCTCGAT

ATAACGCCCTGCTCCTTCGGTGGAGTTTCCGTGATCACGCCAGGCAC

CAATACCAGTAACCAGGTCGCCGTGCTGTATCAGGATGTCAACTGTA

CTGAGGTGCCCGTAGCCATCCATGCGGATCAGCTCACACCAACTTGG

AGGGTGTACAGCACCGGCTCCAATGTATTCCAGACTCGGGCCGGAT

GCCTTATTGGCGCCGAACACGTGAACAATAGTTACGAATGCGATATT

CCAATTGGCGCCGGAATCTGTGCTAGCTACCAGACTCAGACGAACTC

CCCAGGCAGCGCCAGCAGCGTTGCCAGCCAGTCAATCATCGCTTATA

CAATGTCACTTGGAGCCGAAAACTCCGTGGCTTACTCAAACAACAGC

ATCGCCATCCCCACAAACTTCACCATATCCGTGACAACTGAGATTCT

GCCAGTGTCCATGACTAAGACGTCCGTAGATTGCACTATGTACATAT

GCGGCGACAGCACAGAATGTTCTAATCTGCTGCTGCAATATGGAAG

CTTCTGCACTCAACTGAACAGAGCGCTCACAGGCATCGCCGTGGAGC

AGGATAAGAATACCCAGGAGGTGTTCGCCCAAGTTAAGCAGATCTA

CAAGACCCCACCCATAAAGGATTTCGGTGGATTCAATTTTAGTCAGA

TACTCCCAGACCCATCTAAGCCATCCAAGAGGAGCTTTATCGAGGAT

CTTTTGTTTAACAAAGTTACTCTGGCCGACGCCGGTTTCATCAAGCA

GTACGGAGATTGCCTCGGCGACATCGCTGCTCGTGACCTCATCTGTG

CGCAAAAGTTTAACGGTCTGACGGTGCTGCCTCCCCTCCTTACTGAT

GAAATGATCGCCCAGTATACCAGCGCACTCCTCGCTGGCACCATAAC

ATCCGGTTGGACATTCGGCGCTGGTGCAGCACTGCAGATACCATTCG

CCATGCAAATGGCATATCGTTTCAACGGTATCGGTGTCACACAGAAT

GTCCTATATGAGAACCAGAAGCTGATCGCAAATCAGTTCAATAGTGC

CATCGGAAAAATCCAGGATAGCCTTAGCAGCACAGCCTCAGCCCTT

GGCAAACTCCAGGATGTCGTGAACCAGAATGCCCAGGCTCTCAATA

CCCTCGTGAAGCAGCTCTCATCTAATTTCGGCGCAATTTCCAGTGTC

CTCAACGACATCCTCAGCCGCCTCGACCCCCCCGAGGCCGAAGTGCA

GATTGACAGACTGATTACAGGTCGACTCCAGAGCCTCCAGACTTACG

TGACTCAGCAGCTGATAAGAGCCGCCGAGATAAGGGCCAGCGCTAA

CCTGGCTGCCACAAAGATGTCTGAGTGCGTGCTGGGCCAGTCCAAG

AGAGTAGACTTCTGTGGCAAAGGCTACCATCTGATGAGCTTCCCACA

ATCCGCACCTCACGGCGTAGTGTTCCTCCACGTGACATATGTACCGG

CTCAGGAGAAGAATTTCACTACCGCTCCTGCTATATGCCATGATGGA

AAGGCTCACTTCCCCCGGGAGGGGGTGTTCGTGTCCAACGGCACCCA

TTGGTTTGTGACTCAGCGGAATTTCTACGAACCCCAGATCATAACCA

CTGACAACACATTTGTGTCCGGAAATTGTGACGTGGTCATTGGAATA

GTGAACAACACTGTTTATGATCCACTGCAGCCAGAACTTGACAGCTT

TAAGGAGGAGCTCGACAAGTACTTCAAGAATCATACGTCACCAGAT

GTGGACCTCGGAGATATTAGCGGTATCAATGCCAGTGTTGTCAATAT

TCAGAAGGAAATAGACCGCCTTAATGAGGTCGCCAAAAATCTGAAC

GAGAGCCTCATCGATCTTCAGGAGCTGGGCAAATATGAGCAGTACA

TCAAGTGGCCTTGGTATATTTGGCTTGGCTTCATCGCCGGCCTGATC

GCCATAGTAATGGTCACAATTATGCTCTGCTGCATGACCTCTTGCTG

CTCCTGTCTGAAAGGCTGCTGCTCTTGCGGATCCTGCTGCAAATTTG

ATGAGGATGACAGTGAACCAGTCCTGAAGGGCGTGAAGCTGCACTA

TACTTAG

PDI-SARS-CoV-2S protein GSAS+PP wtTM/CT-AA (SEQ ID NO: 23)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

IF(PDI)-CoV(opt2).c(SEQ ID NO：24)

TCTCAGATCTTCGCGGTGAATCTTACGACGCGAACACAGTTACCACCCGCAT

IF(AVB)-CoV(opt2).r(SEQ ID NO：25)

ACGACACGACTAAGGCCTCTAAGTATAGTGCAGCTTCACGCCCTTCAGGAC

PDI-modified SARS-CoV-2S protein GSAS+PP H5iTM/CT-DNA (SEQ ID NO: 26)

ATGGCGAAAAACGTTGCGATTTTCGGCTTATTGTTTTCTCTTCTTGTGTTGGTTCCTTCTCAGATCTTCGCGGTGAATCTTACGACGCGAACACAGTTACCACCCGCATATACAAATAGCTTCACTCGGGGTGTTTATTACCCCGACAAAGTGTTCAGGTCCTCCGTGCTCCACTCAACACAGGACCTCTTTCTTCCTTTCTTTTCTAACGTGACATGGTTTCATGCCATTCATGTATCCGGCACTAACGGTACTAAGAGGTTCGATAATCCTGTGCTCCCTTTCAATGACGGCGTTTACTTTGCAAGCACAGAGAAGAGTAACATCATCCGAGGTTGGATCTTTGGCACTACCCTCGATTCAAAGACGCAGAGCCTC

CTCATTGTGAACAATGCCACTAACGTGGTGATCAAAGTTTGCGAGTT

TCAGTTCTGCAATGACCCTTTCTTGGGGGTGTACTATCATAAGAACA

ACAAGTCTTGGATGGAATCTGAATTCCGCGTCTATAGCAGCGCCAAC

AACTGCACCTTTGAATACGTGTCCCAGCCCTTCCTTATGGACCTGGA

GGGAAAGCAGGGAAACTTTAAGAATCTGAGAGAGTTCGTGTTTAAA

AATATCGACGGCTATTTTAAGATCTATTCTAAGCACACGCCTATTAA

TCTCGTGCGCGATCTTCCACAAGGCTTCAGCGCCCTGGAACCACTCG

TGGACCTCCCAATTGGTATCAACATCACTAGATTTCAGACTCTGCTT

GCCCTCCACCGATCCTATCTGACACCCGGAGACTCCTCTAGCGGCTG

GACTGCCGGCGCTGCCGCTTATTACGTTGGTTATCTTCAGCCACGCA

CGTTCCTGCTGAAGTATAACGAGAATGGTACTATTACCGATGCCGTG

GATTGTGCCCTTGACCCCCTGTCCGAAACTAAGTGCACACTCAAGTC

ATTCACTGTGGAAAAAGGAATCTACCAGACAAGCAATTTTCGGGTCC

AGCCTACTGAGAGCATTGTGCGCTTTCCTAACATCACAAATCTTTGC

CCCTTCGGAGAGGTTTTCAATGCTACACGGTTTGCCTCCGTGTATGC

CTGGAACCGCAAGAGAATTTCCAATTGCGTGGCCGATTACTCCGTGC

TCTACAATAGTGCAAGCTTTAGCACCTTTAAGTGCTATGGCGTATCC

CCTACTAAGCTTAACGACTTGTGTTTCACAAACGTGTATGCCGACTC

CTTTGTGATACGGGGCGACGAAGTTAGACAGATAGCACCAGGACAG

ACGGGAAAGATAGCTGACTACAACTATAAGCTTCCTGATGACTTCAC

TGGCTGCGTTATCGCGTGGAATTCTAACAACCTGGACTCAAAAGTCG

GCGGCAACTATAACTATCTCTATCGGCTGTTCCGCAAGAGTAACCTT

AAGCCCTTTGAGAGAGATATAAGCACTGAAATCTACCAGGCTGGCA

GTACGCCCTGTAATGGCGTGGAAGGCTTTAATTGTTATTTTCCACTG

CAATCCTATGGTTTTCAGCCAACCAATGGCGTGGGCTACCAACCATA

CCGCGTCGTGGTGCTCTCCTTTGAACTGCTCCACGCTCCCGCGACTGT

CTGCGGCCCCAAGAAGTCCACGAACCTTGTGAAGAATAAGTGCGTT

AATTTTAATTTCAACGGCCTCACTGGAACAGGAGTGCTCACTGAGAG

TAACAAGAAGTTCCTGCCATTTCAACAATTTGGCAGAGACATAGCCG

ATACTACTGACGCCGTTAGGGACCCCCAGACCCTCGAGATTCTCGAT

ATAACGCCCTGCTCCTTCGGTGGAGTTTCCGTGATCACGCCAGGCAC

CAATACCAGTAACCAGGTCGCCGTGCTGTATCAGGATGTCAACTGTA

CTGAGGTGCCCGTAGCCATCCATGCGGATCAGCTCACACCAACTTGG

AGGGTGTACAGCACCGGCTCCAATGTATTCCAGACTCGGGCCGGAT

GCCTTATTGGCGCCGAACACGTGAACAATAGTTACGAATGCGATATT

CCAATTGGCGCCGGAATCTGTGCTAGCTACCAGACTCAGACGAACTC

CCCAGGCAGCGCCAGCAGCGTTGCCAGCCAGTCAATCATCGCTTATA

CAATGTCACTTGGAGCCGAAAACTCCGTGGCTTACTCAAACAACAGC

ATCGCCATCCCCACAAACTTCACCATATCCGTGACAACTGAGATTCT

GCCAGTGTCCATGACTAAGACGTCCGTAGATTGCACTATGTACATAT

GCGGCGACAGCACAGAATGTTCTAATCTGCTGCTGCAATATGGAAG

CTTCTGCACTCAACTGAACAGAGCGCTCACAGGCATCGCCGTGGAGC

AGGATAAGAATACCCAGGAGGTGTTCGCCCAAGTTAAGCAGATCTA

CAAGACCCCACCCATAAAGGATTTCGGTGGATTCAATTTTAGTCAGA

TACTCCCAGACCCATCTAAGCCATCCAAGAGGAGCTTTATCGAGGAT

CTTTTGTTTAACAAAGTTACTCTGGCCGACGCCGGTTTCATCAAGCA

GTACGGAGATTGCCTCGGCGACATCGCTGCTCGTGACCTCATCTGTG

CGCAAAAGTTTAACGGTCTGACGGTGCTGCCTCCCCTCCTTACTGAT

GAAATGATCGCCCAGTATACCAGCGCACTCCTCGCTGGCACCATAAC

ATCCGGTTGGACATTCGGCGCTGGTGCAGCACTGCAGATACCATTCG

CCATGCAAATGGCATATCGTTTCAACGGTATCGGTGTCACACAGAAT

GTCCTATATGAGAACCAGAAGCTGATCGCAAATCAGTTCAATAGTGC

CATCGGAAAAATCCAGGATAGCCTTAGCAGCACAGCCTCAGCCCTT

GGCAAACTCCAGGATGTCGTGAACCAGAATGCCCAGGCTCTCAATA

CCCTCGTGAAGCAGCTCTCATCTAATTTCGGCGCAATTTCCAGTGTC

CTCAACGACATCCTCAGCCGCCTCGACCCCCCCGAGGCCGAAGTGCA

GATTGACAGACTGATTACAGGTCGACTCCAGAGCCTCCAGACTTACG

TGACTCAGCAGCTGATAAGAGCCGCCGAGATAAGGGCCAGCGCTAACCTGGCTGCCACAAAGATGTCTGAGTGCGTGCTGGGCCAGTCCAAGAGAGTAGACTTCTGTGGCAAAGGCTACCATCTGATGAGCTTCCCACAATCCGCACCTCACGGCGTAGTGTTCCTCCACGTGACATATGTACCGGCTCAGGAGAAGAATTTCACTACCGCTCCTGCTATATGCCATGATGGAAAGGCTCACTTCCCCCGGGAGGGGGTGTTCGTGTCCAACGGCACCCATTGGTTTGTGACTCAGCGGAATTTCTACGAACCCCAGATCATAACCACTGACAACACATTTGTGTCCGGAAATTGTGACGTGGTCATTGGAATAGTGAACAACACTGTTTATGATCCACTGCAGCCAGAACTTGACAGCTTTAAGGAGGAGCTCGACAAGTACTTCAAGAATCATACGTCACCAGATGTGGACCTCGGAGATATTAGCGGTATCAATGCCAGTGTTGTCAATATTCAGAAGGAAATAGACCGCCTTAATGAGGTCGCCAAAAATCTGAACGAGAGCCTCATCGATCTTCAGGAGCTGGGCAAATATGAGCAGTACATCAAGTGGCCTTGGTATCAAATACTGTCAATTTATTCAACAGTGGCGAGTTCCCTAGCACTGGCAATCATGATGGCTGGTCTATCTTTATGGATGTGCTCCAATGGATCGTTACAATGCAGAATTTGCATTTAA

PDI-modified SARS-CoV-2S protein GSAS+PP H5iTM/CT-AA (SEQ ID NO: 27)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

IF(Avb)-H5I.r(SEQ ID NO：28)

ACGACACGACTAAGGCCTTTAAATGCAAATTCTGCATTGTAACGATCC

PDI-modified SARS-CoV-2S protein GSAS+PP wtTM/H5iCT-DNA (SEQ ID NO: 29)

CTCATTGTGAACAATGCCACTAACGTGGTGATCAAAGTTTGCGAGTT

TCAGTTCTGCAATGACCCTTTCTTGGGGGTGTACTATCATAAGAACA

ACAAGTCTTGGATGGAATCTGAATTCCGCGTCTATAGCAGCGCCAAC

AACTGCACCTTTGAATACGTGTCCCAGCCCTTCCTTATGGACCTGGA

GGGAAAGCAGGGAAACTTTAAGAATCTGAGAGAGTTCGTGTTTAAA

AATATCGACGGCTATTTTAAGATCTATTCTAAGCACACGCCTATTAA

TCTCGTGCGCGATCTTCCACAAGGCTTCAGCGCCCTGGAACCACTCG

TGGACCTCCCAATTGGTATCAACATCACTAGATTTCAGACTCTGCTT

GCCCTCCACCGATCCTATCTGACACCCGGAGACTCCTCTAGCGGCTG

GACTGCCGGCGCTGCCGCTTATTACGTTGGTTATCTTCAGCCACGCA

CGTTCCTGCTGAAGTATAACGAGAATGGTACTATTACCGATGCCGTG

GATTGTGCCCTTGACCCCCTGTCCGAAACTAAGTGCACACTCAAGTC

ATTCACTGTGGAAAAAGGAATCTACCAGACAAGCAATTTTCGGGTCC

AGCCTACTGAGAGCATTGTGCGCTTTCCTAACATCACAAATCTTTGC

CCCTTCGGAGAGGTTTTCAATGCTACACGGTTTGCCTCCGTGTATGC

CTGGAACCGCAAGAGAATTTCCAATTGCGTGGCCGATTACTCCGTGC

TCTACAATAGTGCAAGCTTTAGCACCTTTAAGTGCTATGGCGTATCC

CCTACTAAGCTTAACGACTTGTGTTTCACAAACGTGTATGCCGACTC

CTTTGTGATACGGGGCGACGAAGTTAGACAGATAGCACCAGGACAG

ACGGGAAAGATAGCTGACTACAACTATAAGCTTCCTGATGACTTCAC

TGGCTGCGTTATCGCGTGGAATTCTAACAACCTGGACTCAAAAGTCG

GCGGCAACTATAACTATCTCTATCGGCTGTTCCGCAAGAGTAACCTT

AAGCCCTTTGAGAGAGATATAAGCACTGAAATCTACCAGGCTGGCA

GTACGCCCTGTAATGGCGTGGAAGGCTTTAATTGTTATTTTCCACTG

CAATCCTATGGTTTTCAGCCAACCAATGGCGTGGGCTACCAACCATA

CCGCGTCGTGGTGCTCTCCTTTGAACTGCTCCACGCTCCCGCGACTGT

CTGCGGCCCCAAGAAGTCCACGAACCTTGTGAAGAATAAGTGCGTT

AATTTTAATTTCAACGGCCTCACTGGAACAGGAGTGCTCACTGAGAG

TAACAAGAAGTTCCTGCCATTTCAACAATTTGGCAGAGACATAGCCG

ATACTACTGACGCCGTTAGGGACCCCCAGACCCTCGAGATTCTCGAT

ATAACGCCCTGCTCCTTCGGTGGAGTTTCCGTGATCACGCCAGGCAC

CAATACCAGTAACCAGGTCGCCGTGCTGTATCAGGATGTCAACTGTA

CTGAGGTGCCCGTAGCCATCCATGCGGATCAGCTCACACCAACTTGG

AGGGTGTACAGCACCGGCTCCAATGTATTCCAGACTCGGGCCGGAT

GCCTTATTGGCGCCGAACACGTGAACAATAGTTACGAATGCGATATT

CCAATTGGCGCCGGAATCTGTGCTAGCTACCAGACTCAGACGAACTC

CCCAGGCAGCGCCAGCAGCGTTGCCAGCCAGTCAATCATCGCTTATA

CAATGTCACTTGGAGCCGAAAACTCCGTGGCTTACTCAAACAACAGC

ATCGCCATCCCCACAAACTTCACCATATCCGTGACAACTGAGATTCT

GCCAGTGTCCATGACTAAGACGTCCGTAGATTGCACTATGTACATAT

GCGGCGACAGCACAGAATGTTCTAATCTGCTGCTGCAATATGGAAG

CTTCTGCACTCAACTGAACAGAGCGCTCACAGGCATCGCCGTGGAGC

AGGATAAGAATACCCAGGAGGTGTTCGCCCAAGTTAAGCAGATCTA

CAAGACCCCACCCATAAAGGATTTCGGTGGATTCAATTTTAGTCAGA

TACTCCCAGACCCATCTAAGCCATCCAAGAGGAGCTTTATCGAGGAT

CTTTTGTTTAACAAAGTTACTCTGGCCGACGCCGGTTTCATCAAGCA

GTACGGAGATTGCCTCGGCGACATCGCTGCTCGTGACCTCATCTGTG

CGCAAAAGTTTAACGGTCTGACGGTGCTGCCTCCCCTCCTTACTGAT

GAAATGATCGCCCAGTATACCAGCGCACTCCTCGCTGGCACCATAAC

ATCCGGTTGGACATTCGGCGCTGGTGCAGCACTGCAGATACCATTCG

CCATGCAAATGGCATATCGTTTCAACGGTATCGGTGTCACACAGAAT

GTCCTATATGAGAACCAGAAGCTGATCGCAAATCAGTTCAATAGTGC

CATCGGAAAAATCCAGGATAGCCTTAGCAGCACAGCCTCAGCCCTT

GGCAAACTCCAGGATGTCGTGAACCAGAATGCCCAGGCTCTCAATA

CCCTCGTGAAGCAGCTCTCATCTAATTTCGGCGCAATTTCCAGTGTC

CTCAACGACATCCTCAGCCGCCTCGACCCCCCCGAGGCCGAAGTGCA

GATTGACAGACTGATTACAGGTCGACTCCAGAGCCTCCAGACTTACG

TGACTCAGCAGCTGATAAGAGCCGCCGAGATAAGGGCCAGCGCTAACCTGGCTGCCACAAAGATGTCTGAGTGCGTGCTGGGCCAGTCCAAGAGAGTAGACTTCTGTGGCAAAGGCTACCATCTGATGAGCTTCCCACAATCCGCACCTCACGGCGTAGTGTTCCTCCACGTGACATATGTACCGGCTCAGGAGAAGAATTTCACTACCGCTCCTGCTATATGCCATGATGGAAAGGCTCACTTCCCCCGGGAGGGGGTGTTCGTGTCCAACGGCACCCATTGGTTTGTGACTCAGCGGAATTTCTACGAACCCCAGATCATAACCACTGACAACACATTTGTGTCCGGAAATTGTGACGTGGTCATTGGAATAGTGAACAACACTGTTTATGATCCACTGCAGCCAGAACTTGACAGCTTTAAGGAGGAGCTCGACAAGTACTTCAAGAATCATACGTCACCAGATGTGGACCTCGGAGATATTAGCGGTATCAATGCCAGTGTTGTCAATATTCAGAAGGAAATAGACCGCCTTAATGAGGTCGCCAAAAATCTGAACGAGAGCCTCATCGATCTTCAGGAGCTGGGCAAATATGAGCAGTACATCAAGTGGCCTTGGTATATTTGGCTTGGCTTCATCGCCGGCCTGATCGCCATAGTAATGGTCACAATTATGCTCTCTTTATGGATGTGCTCCAATGGATCGTTACAATGCAGAATTTGCATTTAA

PDI-modified SARS-CoV-2S protein GSAS+PP wtTM/H5iCT-AA (SEQ ID NO: 30)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

Cloning vector 8501 from left to right T-DNA (SEQ ID NO: 31)

tggcaggatatattgtggtgtaaacaaattgacgcttagacaacttaataacacattgcggacgtttttaatgtactg

aattaacgccgaatcccgggctggtatatttatatgttgtcaaataactcaaaaaccataaaagtttaagttagcaa

gtgtgtacatttttacttgaacaaaaatattcacctactactgttataaatcattattaaacattagagtaaagaaatat

ggatgataagaacaagagtagtgatattttgacaacaattttgttgcaacatttgagaaaattttgttgttctctctttt

cattggtcaaaaacaatagagagagaaaaaggaagagggagaataaaaacataatgtgagtatgagagagaa

agttgtacaaaagttgtaccaaaatagttgtacaaatatcattgaggaatttgacaaaagctacacaaataagggtt

aattgctgtaaataaataaggatgacgcattagagagatgtaccattagagaatttttggcaagtcattaaaaaga

aagaataaattatttttaaaattaaaagttgagtcatttgattaaacatgtgattatttaatgaattgatgaaagagttg

gattaaagttgtattagtaattagaatttggtgtcaaatttaatttgacatttgatcttttcctatatattgccccatagag

tcagttaactcatttttatatttcatagatcaaataagagaaataacggtatattaatccctccaaaaaaaaaaaacg

gtatatttactaaaaaatctaagccacgtaggaggataacaggatccccgtaggaggataacatccaatccaacc

aatcacaacaatcctgatgagataacccactttaagcccacgcatctgtggcacatctacattatctaaatcacac

attcttccacacatctgagccacacaaaaaccaatccacatctttatcacccattctataaaaaatcacactttgtga

gtctacactttgattcccttcaaacacatacaaagagaagagactaattaattaattaatcatcttgagagaaaatg

gaacgagctatacaaggaaacgacgctagggaacaagctaacagtgaacgttgggatggaggatcaggagg

taccacttctcccttcaaacttcctgacgaaagtccgagttggactgagtggcggctacataacgatgagacgaa

ttcgaatcaagataatccccttggtttcaaggaaagctggggtttcgggaaagttgtatttaagagatatctcagat

acgacaggacggaagcttcactgcacagagtccttggatcttggacgggagattcggttaactatgcagcatct

cgatttttcggtttcgaccagatcggatgtacctatagtattcggtttcgaggagttagtatcaccgtttctggaggg

tcgcgaactcttcagcatctctgtgagatggcaattcggtctaagcaagaactgctacagcttgccccaatcgaa

gtggaaagtaatgtatcaagaggatgccctgaaggtactcaaaccttcgaaaaagaaagcgagtaagttaaaat

gcttcttcgtctcctatttataatatggtttgttattgttaattttgttcttgtagaagagcttaattaatcgttgttgttatg

aaatactatttgtatgagatgaactggtgtaatgtaattcatttacataagtggagtcagaatcagaatgtttcctcca

taactaactagacatgaagacctgccgcgtacaattgtcttatatttgaacaactaaaattgaacatcttttgccaca

actttataagtggttaatatagctcaaatatatggtcaagttcaatagattaataatggaaatatcagttatcgaaatt

cattaacaatcaacttaacgttattaactactaattttatatcatcccctttgataaatgatagtacaccaattaggaag

gagcatgctcgcctaggagattgtcgtttcccgccttcagtttgcaagctgctctagccgtgtagccaatacgcaa

accgcctctccccgcgcgttgggaattactagcgcgtgtcgacaagcttgcatgccggtcaacatggtggagca

cgacacacttgtctactccaaaaatatcaaagatacagtctcagaagaccaaagggcaattgagacttttcaaca

aagggtaatatccggaaacctcctcggattccattgcccagctatctgtcactttattgtgaagatagtggaaaag

gaaggtggctcctacaaatgccatcattgcgataaaggaaaggccatcgttgaagatgcctctgccgacagtgg

tcccaaagatggacccccacccacgaggagcatcgtggaaaaagaagacgttccaaccacgtcttcaaagca

agtggattgatgtgataacatggtggagcacgacacacttgtctactccaaaaatatcaaagatacagtctcaga

agaccaaagggcaattgagacttttcaacaaagggtaatatccggaaacctcctcggattccattgcccagctat

ctgtcactttattgtgaagatagtggaaaaggaaggtggctcctacaaatgccatcattgcgataaaggaaaggc

catcgttgaagatgcctctgccgacagtggtcccaaagatggacccccacccacgaggagcatcgtggaaaaa

gaagacgttccaaccacgtcttcaaagcaagtggattgatgtgatatctccactgacgtaagggatgacgcaca

atcccactatccttcgcaagacccttcctctatataaggaagttcatttcatttggagaggcacacaatttgctttagt

gattaaactttcttttacaacaaattaaaggtctattatctcccaacaacataagaaaacaatggcgaaaaacgttg

cgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgacgtcactcctcagccaaaacgac

acccccatctgtctatccactggcccctggatctgctgcccaaactaactccatggtgaccctgggatgcctggt

caagggctatttccctgagccagtgacagtgacctggaactctggatccctgtccagcggtgtgcacaccttccc

agctgtcctgcagtctgacctctacactctgagcagctcagtgactgtcccctccagcacctggcccagcgaga

ccgtcacctgcaacgttgcccacccggccagcagcaccaaggtggacaagaaaattgtgcccagggattgtg

gttgtaagccttgcatatgtacagtcccagaagtatcatctgtcttcatcttccccccaaagcccaaggatgtgctc

accattactctgactcctaaggtcacgtgtgttgtggtagacatcagcaaggatgatcccgaggtccagttcagct

ggtttgtagatgatgtggaggtgcacacagctcagacgcaaccccgggaggagcagttcaacagcactttccg

ctcagtcagtgaacttcccatcatgcaccaggactggctcaatggcaaggagacgtccagattttggcgatctat

tcaactgtcgccagttcattggtactggtagtctccctgggggcaatcagtttctggatgtgctctaatgggtctcta

cagtgtagaatatgtatttaaaggccttagtcgtgtcgtttttcaaataatataatccttttagggttttagttagtttaaa

ttttctgttgctcctgtttagcaggtcgtgccttcagcaagcacacaaaaacagagtgtttattttaagttgtttgttta

gtgattcaaaaaaaaaatcgttcaaacatttggcaataaagtttcttaagattgaatcctgttgccggtcttgcgatg

attatcatataatttctgttgaattacgttaagcatgtaataattaacatgtaatgcatgacgttatttatgagatgggtt

tttatgattagagtcccgcaattatacatttaatacgcgatagaaaacaaaatatagcgcgcaaactaggataaatt

atcgcgcgcggtgtcatctatgttactagatctctagagtctcaagcttggcgcgcccacgtgactagtggcact

ggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgcagcacatccccc

tttcgccagctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggc

gaatgctagagcagcttgagcttggatcagattgtcgtttcccgccttcagtttaaactatcagtgtttgacaggat

atattggcgggtaaacctaagagaaaagagcgttta

Construct 8586 from 2X35S prom to NOS terminator (SEQ ID NO: 32)

GTCAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCAA

AGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACAA

AGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCTG

TCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAAAT

GCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTGCC

GACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGTGG

AAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATG

TGATAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCA

AAGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACA

AAGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCT

GTCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAA

ATGCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTG

CCGACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGT

GGAAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGA

TGTGATATCTCCACTGACGTAAGGGATGACGCACAATCCCACTATCC

TTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTCATTTGGAGA

GGCACACAATTTGCTTTAGTGATTAAACTTTCTTTTACAACAAATTA

AAGGTCTATTATCTCCCAACAACATAAGAAAACAATGGCGAAAAAC

GTTGCGATTTTCGGCTTATTGTTTTCTCTTCTTGTGTTGGTTCCTTCTC

AGATCTTCGCGGTGAATCTTACGACGCGAACACAGTTACCACCCGCA

TATACAAATAGCTTCACTCGGGGTGTTTATTACCCCGACAAAGTGTT

CAGGTCCTCCGTGCTCCACTCAACACAGGACCTCTTTCTTCCTTTCTT

TTCTAACGTGACATGGTTTCATGCCATTCATGTATCCGGCACTAACG

GTACTAAGAGGTTCGATAATCCTGTGCTCCCTTTCAATGACGGCGTT

TACTTTGCAAGCACAGAGAAGAGTAACATCATCCGAGGTTGGATCTT

TGGCACTACCCTCGATTCAAAGACGCAGAGCCTCCTCATTGTGAACA

ATGCCACTAACGTGGTGATCAAAGTTTGCGAGTTTCAGTTCTGCAAT

GACCCTTTCTTGGGGGTGTACTATCATAAGAACAACAAGTCTTGGAT

GGAATCTGAATTCCGCGTCTATAGCAGCGCCAACAACTGCACCTTTG

AATACGTGTCCCAGCCCTTCCTTATGGACCTGGAGGGAAAGCAGGG

AAACTTTAAGAATCTGAGAGAGTTCGTGTTTAAAAATATCGACGGCT

ATTTTAAGATCTATTCTAAGCACACGCCTATTAATCTCGTGCGCGAT

CTTCCACAAGGCTTCAGCGCCCTGGAACCACTCGTGGACCTCCCAAT

TGGTATCAACATCACTAGATTTCAGACTCTGCTTGCCCTCCACCGAT

CCTATCTGACACCCGGAGACTCCTCTAGCGGCTGGACTGCCGGCGCT

GCCGCTTATTACGTTGGTTATCTTCAGCCACGCACGTTCCTGCTGAA

GTATAACGAGAATGGTACTATTACCGATGCCGTGGATTGTGCCCTTG

ACCCCCTGTCCGAAACTAAGTGCACACTCAAGTCATTCACTGTGGAA

AAAGGAATCTACCAGACAAGCAATTTTCGGGTCCAGCCTACTGAGA

GCATTGTGCGCTTTCCTAACATCACAAATCTTTGCCCCTTCGGAGAG

GTTTTCAATGCTACACGGTTTGCCTCCGTGTATGCCTGGAACCGCAA

GAGAATTTCCAATTGCGTGGCCGATTACTCCGTGCTCTACAATAGTG

CAAGCTTTAGCACCTTTAAGTGCTATGGCGTATCCCCTACTAAGCTT

AACGACTTGTGTTTCACAAACGTGTATGCCGACTCCTTTGTGATACG

GGGCGACGAAGTTAGACAGATAGCACCAGGACAGACGGGAAAGAT

AGCTGACTACAACTATAAGCTTCCTGATGACTTCACTGGCTGCGTTA

TCGCGTGGAATTCTAACAACCTGGACTCAAAAGTCGGCGGCAACTAT

AACTATCTCTATCGGCTGTTCCGCAAGAGTAACCTTAAGCCCTTTGA

GAGAGATATAAGCACTGAAATCTACCAGGCTGGCAGTACGCCCTGT

AATGGCGTGGAAGGCTTTAATTGTTATTTTCCACTGCAATCCTATGG

TTTTCAGCCAACCAATGGCGTGGGCTACCAACCATACCGCGTCGTGG

TGCTCTCCTTTGAACTGCTCCACGCTCCCGCGACTGTCTGCGGCCCCA

AGAAGTCCACGAACCTTGTGAAGAATAAGTGCGTTAATTTTAATTTC

AACGGCCTCACTGGAACAGGAGTGCTCACTGAGAGTAACAAGAAGT

TCCTGCCATTTCAACAATTTGGCAGAGACATAGCCGATACTACTGAC

GCCGTTAGGGACCCCCAGACCCTCGAGATTCTCGATATAACGCCCTG

CTCCTTCGGTGGAGTTTCCGTGATCACGCCAGGCACCAATACCAGTA

ACCAGGTCGCCGTGCTGTATCAGGATGTCAACTGTACTGAGGTGCCC

GTAGCCATCCATGCGGATCAGCTCACACCAACTTGGAGGGTGTACA

GCACCGGCTCCAATGTATTCCAGACTCGGGCCGGATGCCTTATTGGC

GCCGAACACGTGAACAATAGTTACGAATGCGATATTCCAATTGGCG

CCGGAATCTGTGCTAGCTACCAGACTCAGACGAACTCCCCAGGCAG

CGCCAGCAGCGTTGCCAGCCAGTCAATCATCGCTTATACAATGTCAC

TTGGAGCCGAAAACTCCGTGGCTTACTCAAACAACAGCATCGCCATC

CCCACAAACTTCACCATATCCGTGACAACTGAGATTCTGCCAGTGTC

CATGACTAAGACGTCCGTAGATTGCACTATGTACATATGCGGCGACA

GCACAGAATGTTCTAATCTGCTGCTGCAATATGGAAGCTTCTGCACT

CAACTGAACAGAGCGCTCACAGGCATCGCCGTGGAGCAGGATAAGA

ATACCCAGGAGGTGTTCGCCCAAGTTAAGCAGATCTACAAGACCCC

ACCCATAAAGGATTTCGGTGGATTCAATTTTAGTCAGATACTCCCAG

ACCCATCTAAGCCATCCAAGAGGAGCTTTATCGAGGATCTTTTGTTT

AACAAAGTTACTCTGGCCGACGCCGGTTTCATCAAGCAGTACGGAG

ATTGCCTCGGCGACATCGCTGCTCGTGACCTCATCTGTGCGCAAAAG

TTTAACGGTCTGACGGTGCTGCCTCCCCTCCTTACTGATGAAATGAT

CGCCCAGTATACCAGCGCACTCCTCGCTGGCACCATAACATCCGGTT

GGACATTCGGCGCTGGTGCAGCACTGCAGATACCATTCGCCATGCAA

ATGGCATATCGTTTCAACGGTATCGGTGTCACACAGAATGTCCTATA

TGAGAACCAGAAGCTGATCGCAAATCAGTTCAATAGTGCCATCGGA

AAAATCCAGGATAGCCTTAGCAGCACAGCCTCAGCCCTTGGCAAAC

TCCAGGATGTCGTGAACCAGAATGCCCAGGCTCTCAATACCCTCGTG

AAGCAGCTCTCATCTAATTTCGGCGCAATTTCCAGTGTCCTCAACGA

CATCCTCAGCCGCCTCGACCCCCCCGAGGCCGAAGTGCAGATTGACA

GACTGATTACAGGTCGACTCCAGAGCCTCCAGACTTACGTGACTCAG

CAGCTGATAAGAGCCGCCGAGATAAGGGCCAGCGCTAACCTGGCTG

CCACAAAGATGTCTGAGTGCGTGCTGGGCCAGTCCAAGAGAGTAGA

CTTCTGTGGCAAAGGCTACCATCTGATGAGCTTCCCACAATCCGCAC

CTCACGGCGTAGTGTTCCTCCACGTGACATATGTACCGGCTCAGGAG

AAGAATTTCACTACCGCTCCTGCTATATGCCATGATGGAAAGGCTCA

CTTCCCCCGGGAGGGGGTGTTCGTGTCCAACGGCACCCATTGGTTTG

TGACTCAGCGGAATTTCTACGAACCCCAGATCATAACCACTGACAAC

ACATTTGTGTCCGGAAATTGTGACGTGGTCATTGGAATAGTGAACAA

CACTGTTTATGATCCACTGCAGCCAGAACTTGACAGCTTTAAGGAGG

AGCTCGACAAGTACTTCAAGAATCATACGTCACCAGATGTGGACCTC

GGAGATATTAGCGGTATCAATGCCAGTGTTGTCAATATTCAGAAGGA

AATAGACCGCCTTAATGAGGTCGCCAAAAATCTGAACGAGAGCCTC

ATCGATCTTCAGGAGCTGGGCAAATATGAGCAGTACATCAAGTGGC

CTTGGTATATTTGGCTTGGCTTCATCGCCGGCCTGATCGCCATAGTA

ATGGTCACAATTATGCTCTGCTGCATGACCTCTTGCTGCTCCTGTCTG

AAAGGCTGCTGCTCTTGCGGATCCTGCTGCAAATTTGATGAGGATGA

CAGTGAACCAGTCCTGAAGGGCGTGAAGCTGCACTATACTTAGAGG

CCTTAGTCGTGTCGTTTTTCAAATAATATAATCCTTTTAGGGTTTTAG

TTAGTTTAAATTTTCTGTTGCTCCTGTTTAGCAGGTCGTGCCTTCAGC

AAGCACACAAAAACAGAGTGTTTATTTTAAGTTGTTTGTTTAGTGAT

TCAAAAAAAAAATCGTTCAAACATTTGGCAATAAAGTTTCTTAAGAT

TGAATCCTGTTGCCGGTCTTGCGATGATTATCATATAATTTCTGTTGA

ATTACGTTAAGCATGTAATAATTAACATGTAATGCATGACGTTATTT

ATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAATA

CGCGATAGAAAACAAAATATAGCGCGCAAACTAGGATAAATTATCG

CGCGCGGTGTCATCTATGTTACTAGAT

Cloning vector 8500 from left to right T-DNA (SEQ ID NO: 33)

tggcaggatatattgtggtgtaaacaaattgacgcttagacaacttaataacacattgcggacgtttttaatgtactg

aattaacgccgaatcccgggctggtatatttatatgttgtcaaataactcaaaaaccataaaagtttaagttagcaa

cattggtcaaaaacaatagagagagaaaaaggaagagggagaataaaaacataatgtgagtatgagagagaa

agttgtacaaaagttgtaccaaaatagttgtacaaatatcattgaggaatttgacaaaagctacacaaataagggtt

aattgctgtaaataaataaggatgacgcattagagagatgtaccattagagaatttttggcaagtcattaaaaaga

tcagttaactcatttttatatttcatagatcaaataagagaaataacggtatattaatccctccaaaaaaaaaaaacg

gtatatttactaaaaaatctaagccacgtaggaggataacaggatccccgtaggaggataacatccaatccaacc

aatcacaacaatcctgatgagataacccactttaagcccacgcatctgtggcacatctacattatctaaatcacac

attcttccacacatctgagccacacaaaaaccaatccacatctttatcacccattctataaaaaatcacactttgtga

gtctacactttgattcccttcaaacacatacaaagagaagagactaattaattaattaatcatcttgagagaaaatg

gaacgagctatacaaggaaacgacgctagggaacaagctaacagtgaacgttgggatggaggatcaggagg

taccacttctcccttcaaacttcctgacgaaagtccgagttggactgagtggcggctacataacgatgagacgaa

ttcgaatcaagataatccccttggtttcaaggaaagctggggtttcgggaaagttgtatttaagagatatctcagat

acgacaggacggaagcttcactgcacagagtccttggatcttggacgggagattcggttaactatgcagcatct

cgatttttcggtttcgaccagatcggatgtacctatagtattcggtttcgaggagttagtatcaccgtttctggaggg

tcgcgaactcttcagcatctctgtgagatggcaattcggtctaagcaagaactgctacagcttgccccaatcgaa

gtggaaagtaatgtatcaagaggatgccctgaaggtactcaaaccttcgaaaaagaaagcgagtaagttaaaat

aaatactatttgtatgagatgaactggtgtaatgtaattcatttacataagtggagtcagaatcagaatgtttcctcca

taactaactagacatgaagacctgccgcgtacaattgtcttatatttgaacaactaaaattgaacatcttttgccaca

actttataagtggttaatatagctcaaatatatggtcaagttcaatagattaataatggaaatatcagttatcgaaatt

gagcatgctcgcctaggagattgtcgtttcccgccttcagtttgcaagctgctctagccgtgtagccaatacgcaa

accgcctctccccgcgcgttgggaattactagcgcgtgtcgacaagcttgcatgccggtcaacatggtggagca

cgacacacttgtctactccaaaaatatcaaagatacagtctcagaagaccaaagggcaattgagacttttcaaca

aagggtaatatccggaaacctcctcggattccattgcccagctatctgtcactttattgtgaagatagtggaaaag

gaaggtggctcctacaaatgccatcattgcgataaaggaaaggccatcgttgaagatgcctctgccgacagtgg

tcccaaagatggacccccacccacgaggagcatcgtggaaaaagaagacgttccaaccacgtcttcaaagca

agtggattgatgtgataacatggtggagcacgacacacttgtctactccaaaaatatcaaagatacagtctcaga

agaccaaagggcaattgagacttttcaacaaagggtaatatccggaaacctcctcggattccattgcccagctat

ctgtcactttattgtgaagatagtggaaaaggaaggtggctcctacaaatgccatcattgcgataaaggaaaggc

catcgttgaagatgcctctgccgacagtggtcccaaagatggacccccacccacgaggagcatcgtggaaaaa

gaagacgttccaaccacgtcttcaaagcaagtggattgatgtgatatctccactgacgtaagggatgacgcaca

atcccactatccttcgcaagacccttcctctatataaggaagttcatttcatttggagaggcacttttctaatcaatca

tcaaacagaacgcagaaaatttcctaaaaacaaaaaaaaggcatacaaatggcgaaaaacgttgcgattttcgg

cttattgttttctcttcttgtgttggttccttctcagatcttcgcgacgtcactcctcagccaaaacgacacccccatct

gtctatccactggcccctggatctgctgcccaaactaactccatggtgaccctgggatgcctggtcaagggctat

ttccctgagccagtgacagtgacctggaactctggatccctgtccagcggtgtgcacaccttcccagctgtcctg

cagtctgacctctacactctgagcagctcagtgactgtcccctccagcacctggcccagcgagaccgtcacctg

caacgttgcccacccggccagcagcaccaaggtggacaagaaaattgtgcccagggattgtggttgtaagcct

tgcatatgtacagtcccagaagtatcatctgtcttcatcttccccccaaagcccaaggatgtgctcaccattactct

gactcctaaggtcacgtgtgttgtggtagacatcagcaaggatgatcccgaggtccagttcagctggtttgtagat

gatgtggaggtgcacacagctcagacgcaaccccgggaggagcagttcaacagcactttccgctcagtcagt

gaacttcccatcatgcaccaggactggctcaatggcaaggagacgtccagattttggcgatctattcaactgtcg

ccagttcattggtactggtagtctccctgggggcaatcagtttctggatgtgctctaatgggtctctacagtgtaga

atatgtatttaaaggccttagtcgtgtcgtttttcaaataatataatccttttagggttttagttagtttaaattttctgttg

ctcctgtttagcaggtcgtgccttcagcaagcacacaaaaacagagtgtttattttaagttgtttgtttagtgattcaa

aaaaaaaatcgttcaaacatttggcaataaagtttcttaagattgaatcctgttgccggtcttgcgatgattatcatat

aatttctgttgaattacgttaagcatgtaataattaacatgtaatgcatgacgttatttatgagatgggtttttatgatta

gagtcccgcaattatacatttaatacgcgatagaaaacaaaatatagcgcgcaaactaggataaattatcgcgcg

cggtgtcatctatgttactagatctctagagtctcaagcttggcgcgcccacgtgactagtggcactggccgtcgt

tttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagc

tggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgctaga

gcagcttgagcttggatcagattgtcgtttcccgccttcagtttaaactatcagtgtttgacaggatatattggcggg

taaacctaagagaaaagagcgttta

Construct 8589 from 2X35S prom to NOS terminator (SEQ ID NO: 34)

GTCAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCAA

AGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACAA

AGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCTG

TCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAAAT

GCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTGCC

GACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGTGG

AAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATG

TGATAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCA

AAGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACA

AAGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCT

GTCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAA

ATGCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTG

CCGACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGT

GGAAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGA

TGTGATATCTCCACTGACGTAAGGGATGACGCACAATCCCACTATCC

TTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTCATTTGGAGA

GGCACTTTTCTAATCAATCATCAAACAGAACGCAGAAAATTTCCTAA

AAACAAAAAAAAGGCATACAAATGGCGAAAAACGTTGCGATTTTCG

GCTTATTGTTTTCTCTTCTTGTGTTGGTTCCTTCTCAGATCTTCGCGGT

GAATCTTACGACGCGAACACAGTTACCACCCGCATATACAAATAGCT

TCACTCGGGGTGTTTATTACCCCGACAAAGTGTTCAGGTCCTCCGTG

CTCCACTCAACACAGGACCTCTTTCTTCCTTTCTTTTCTAACGTGACA

TGGTTTCATGCCATTCATGTATCCGGCACTAACGGTACTAAGAGGTT

CGATAATCCTGTGCTCCCTTTCAATGACGGCGTTTACTTTGCAAGCA

CAGAGAAGAGTAACATCATCCGAGGTTGGATCTTTGGCACTACCCTC

GATTCAAAGACGCAGAGCCTCCTCATTGTGAACAATGCCACTAACGT

GGTGATCAAAGTTTGCGAGTTTCAGTTCTGCAATGACCCTTTCTTGG

GGGTGTACTATCATAAGAACAACAAGTCTTGGATGGAATCTGAATTC

CGCGTCTATAGCAGCGCCAACAACTGCACCTTTGAATACGTGTCCCA

GCCCTTCCTTATGGACCTGGAGGGAAAGCAGGGAAACTTTAAGAAT

CTGAGAGAGTTCGTGTTTAAAAATATCGACGGCTATTTTAAGATCTA

TTCTAAGCACACGCCTATTAATCTCGTGCGCGATCTTCCACAAGGCT

TCAGCGCCCTGGAACCACTCGTGGACCTCCCAATTGGTATCAACATC

ACTAGATTTCAGACTCTGCTTGCCCTCCACCGATCCTATCTGACACCC

GGAGACTCCTCTAGCGGCTGGACTGCCGGCGCTGCCGCTTATTACGT

TGGTTATCTTCAGCCACGCACGTTCCTGCTGAAGTATAACGAGAATG

GTACTATTACCGATGCCGTGGATTGTGCCCTTGACCCCCTGTCCGAA

ACTAAGTGCACACTCAAGTCATTCACTGTGGAAAAAGGAATCTACC

AGACAAGCAATTTTCGGGTCCAGCCTACTGAGAGCATTGTGCGCTTT

CCTAACATCACAAATCTTTGCCCCTTCGGAGAGGTTTTCAATGCTAC

ACGGTTTGCCTCCGTGTATGCCTGGAACCGCAAGAGAATTTCCAATT

GCGTGGCCGATTACTCCGTGCTCTACAATAGTGCAAGCTTTAGCACC

TTTAAGTGCTATGGCGTATCCCCTACTAAGCTTAACGACTTGTGTTTC

ACAAACGTGTATGCCGACTCCTTTGTGATACGGGGCGACGAAGTTAG

ACAGATAGCACCAGGACAGACGGGAAAGATAGCTGACTACAACTAT

AAGCTTCCTGATGACTTCACTGGCTGCGTTATCGCGTGGAATTCTAA

CAACCTGGACTCAAAAGTCGGCGGCAACTATAACTATCTCTATCGGC

TGTTCCGCAAGAGTAACCTTAAGCCCTTTGAGAGAGATATAAGCACT

GAAATCTACCAGGCTGGCAGTACGCCCTGTAATGGCGTGGAAGGCT

TTAATTGTTATTTTCCACTGCAATCCTATGGTTTTCAGCCAACCAATG

GCGTGGGCTACCAACCATACCGCGTCGTGGTGCTCTCCTTTGAACTG

CTCCACGCTCCCGCGACTGTCTGCGGCCCCAAGAAGTCCACGAACCT

TGTGAAGAATAAGTGCGTTAATTTTAATTTCAACGGCCTCACTGGAA

CAGGAGTGCTCACTGAGAGTAACAAGAAGTTCCTGCCATTTCAACA

ATTTGGCAGAGACATAGCCGATACTACTGACGCCGTTAGGGACCCCC

AGACCCTCGAGATTCTCGATATAACGCCCTGCTCCTTCGGTGGAGTT

TCCGTGATCACGCCAGGCACCAATACCAGTAACCAGGTCGCCGTGCT

GTATCAGGATGTCAACTGTACTGAGGTGCCCGTAGCCATCCATGCGG

ATCAGCTCACACCAACTTGGAGGGTGTACAGCACCGGCTCCAATGTA

TTCCAGACTCGGGCCGGATGCCTTATTGGCGCCGAACACGTGAACAA

TAGTTACGAATGCGATATTCCAATTGGCGCCGGAATCTGTGCTAGCT

ACCAGACTCAGACGAACTCCCCAGGCAGCGCCAGCAGCGTTGCCAG

CCAGTCAATCATCGCTTATACAATGTCACTTGGAGCCGAAAACTCCG

TGGCTTACTCAAACAACAGCATCGCCATCCCCACAAACTTCACCATA

TCCGTGACAACTGAGATTCTGCCAGTGTCCATGACTAAGACGTCCGT

AGATTGCACTATGTACATATGCGGCGACAGCACAGAATGTTCTAATC

TGCTGCTGCAATATGGAAGCTTCTGCACTCAACTGAACAGAGCGCTC

ACAGGCATCGCCGTGGAGCAGGATAAGAATACCCAGGAGGTGTTCG

CCCAAGTTAAGCAGATCTACAAGACCCCACCCATAAAGGATTTCGGT

GGATTCAATTTTAGTCAGATACTCCCAGACCCATCTAAGCCATCCAA

GAGGAGCTTTATCGAGGATCTTTTGTTTAACAAAGTTACTCTGGCCG

ACGCCGGTTTCATCAAGCAGTACGGAGATTGCCTCGGCGACATCGCT

GCTCGTGACCTCATCTGTGCGCAAAAGTTTAACGGTCTGACGGTGCT

GCCTCCCCTCCTTACTGATGAAATGATCGCCCAGTATACCAGCGCAC

TCCTCGCTGGCACCATAACATCCGGTTGGACATTCGGCGCTGGTGCA

GCACTGCAGATACCATTCGCCATGCAAATGGCATATCGTTTCAACGG

TATCGGTGTCACACAGAATGTCCTATATGAGAACCAGAAGCTGATCG

CAAATCAGTTCAATAGTGCCATCGGAAAAATCCAGGATAGCCTTAG

CAGCACAGCCTCAGCCCTTGGCAAACTCCAGGATGTCGTGAACCAG

AATGCCCAGGCTCTCAATACCCTCGTGAAGCAGCTCTCATCTAATTT

CGGCGCAATTTCCAGTGTCCTCAACGACATCCTCAGCCGCCTCGACC

CCCCCGAGGCCGAAGTGCAGATTGACAGACTGATTACAGGTCGACT

CCAGAGCCTCCAGACTTACGTGACTCAGCAGCTGATAAGAGCCGCC

GAGATAAGGGCCAGCGCTAACCTGGCTGCCACAAAGATGTCTGAGT

GCGTGCTGGGCCAGTCCAAGAGAGTAGACTTCTGTGGCAAAGGCTA

CCATCTGATGAGCTTCCCACAATCCGCACCTCACGGCGTAGTGTTCC

TCCACGTGACATATGTACCGGCTCAGGAGAAGAATTTCACTACCGCT

CCTGCTATATGCCATGATGGAAAGGCTCACTTCCCCCGGGAGGGGGT

GTTCGTGTCCAACGGCACCCATTGGTTTGTGACTCAGCGGAATTTCT

ACGAACCCCAGATCATAACCACTGACAACACATTTGTGTCCGGAAAT

TGTGACGTGGTCATTGGAATAGTGAACAACACTGTTTATGATCCACT

GCAGCCAGAACTTGACAGCTTTAAGGAGGAGCTCGACAAGTACTTC

AAGAATCATACGTCACCAGATGTGGACCTCGGAGATATTAGCGGTA

TCAATGCCAGTGTTGTCAATATTCAGAAGGAAATAGACCGCCTTAAT

GAGGTCGCCAAAAATCTGAACGAGAGCCTCATCGATCTTCAGGAGC

TGGGCAAATATGAGCAGTACATCAAGTGGCCTTGGTATATTTGGCTT

GGCTTCATCGCCGGCCTGATCGCCATAGTAATGGTCACAATTATGCT

CTGCTGCATGACCTCTTGCTGCTCCTGTCTGAAAGGCTGCTGCTCTTG

CGGATCCTGCTGCAAATTTGATGAGGATGACAGTGAACCAGTCCTGA

AGGGCGTGAAGCTGCACTATACTTAGAGGCCTTAGTCGTGTCGTTTT

TCAAATAATATAATCCTTTTAGGGTTTTAGTTAGTTTAAATTTTCTGT

TGCTCCTGTTTAGCAGGTCGTGCCTTCAGCAAGCACACAAAAACAGA

GTGTTTATTTTAAGTTGTTTGTTTAGTGATTCAAAAAAAAAATCGTTC

AAACATTTGGCAATAAAGTTTCTTAAGATTGAATCCTGTTGCCGGTC

TTGCGATGATTATCATATAATTTCTGTTGAATTACGTTAAGCATGTAA

TAATTAACATGTAATGCATGACGTTATTTATGAGATGGGTTTTTATG

ATTAGAGTCCCGCAATTATACATTTAATACGCGATAGAAAACAAAAT

ATAGCGCGCAAACTAGGATAAATTATCGCGCGCGGTGTCATCTATGT

TACTAGAT

Cloning vector 8716 from left to right T-DNA (SEQ ID NO: 35)

tggcaggatatattgtggtgtaaacaaattgacgcttagacaacttaataacacattgcggacgtttttaatgtactg

aattaacgccgaatcccgggctggtatatttatatgttgtcaaataactcaaaaaccataaaagtttaagttagcaa

cattggtcaaaaacaatagagagagaaaaaggaagagggagaataaaaacataatgtgagtatgagagagaa

agttgtacaaaagttgtaccaaaatagttgtacaaatatcattgaggaatttgacaaaagctacacaaataagggtt

aattgctgtaaataaataaggatgacgcattagagagatgtaccattagagaatttttggcaagtcattaaaaaga

tcagttaactcatttttatatttcatagatcaaataagagaaataacggtatattaatccctccaaaaaaaaaaaacg

gtatatttactaaaaaatctaagccacgtaggaggataacaggatccccgtaggaggataacatccaatccaacc

aatcacaacaatcctgatgagataacccactttaagcccacgcatctgtggcacatctacattatctaaatcacac

attcttccacacatctgagccacacaaaaaccaatccacatctttatcacccattctataaaaaatcacactttgtga

gtctacactttgattcccttcaaacacatacaaagagaagagactaattaattaattaatcatcttgagagaaaatg

gaacgagctatacaaggaaacgacgctagggaacaagctaacagtgaacgttgggatggaggatcaggagg

taccacttctcccttcaaacttcctgacgaaagtccgagttggactgagtggcggctacataacgatgagacgaa

ttcgaatcaagataatccccttggtttcaaggaaagctggggtttcgggaaagttgtatttaagagatatctcagat

acgacaggacggaagcttcactgcacagagtccttggatcttggacgggagattcggttaactatgcagcatct

cgatttttcggtttcgaccagatcggatgtacctatagtattcggtttcgaggagttagtatcaccgtttctggaggg

tcgcgaactcttcagcatctctgtgagatggcaattcggtctaagcaagaactgctacagcttgccccaatcgaa

gtggaaagtaatgtatcaagaggatgccctgaaggtactcaaaccttcgaaaaagaaagcgagtaagttaaaat

aaatactatttgtatgagatgaactggtgtaatgtaattcatttacataagtggagtcagaatcagaatgtttcctcca

taactaactagacatgaagacctgccgcgtacaattgtcttatatttgaacaactaaaattgaacatcttttgccaca

actttataagtggttaatatagctcaaatatatggtcaagttcaatagattaataatggaaatatcagttatcgaaatt

gagcatgctcgcctaggagattgtcgtttcccgccttcagtttgcaagctgctctagccgtgtagccaatacgcaa

accgcctctccccgcgcgttgggaattactagcgcgtgtcgacaagcttgcatgccggtcaacatggtggagca

cgacacacttgtctactccaaaaatatcaaagatacagtctcagaagaccaaagggcaattgagacttttcaaca

aagggtaatatccggaaacctcctcggattccattgcccagctatctgtcactttattgtgaagatagtggaaaag

gaaggtggctcctacaaatgccatcattgcgataaaggaaaggccatcgttgaagatgcctctgccgacagtgg

tcccaaagatggacccccacccacgaggagcatcgtggaaaaagaagacgttccaaccacgtcttcaaagca

agtggattgatgtgataacatggtggagcacgacacacttgtctactccaaaaatatcaaagatacagtctcaga

agaccaaagggcaattgagacttttcaacaaagggtaatatccggaaacctcctcggattccattgcccagctat

ctgtcactttattgtgaagatagtggaaaaggaaggtggctcctacaaatgccatcattgcgataaaggaaaggc

catcgttgaagatgcctctgccgacagtggtcccaaagatggacccccacccacgaggagcatcgtggaaaaa

gaagacgttccaaccacgtcttcaaagcaagtggattgatgtgatatctccactgacgtaagggatgacgcaca

atcccactatccttcgcaagacccttcctctatataaggaagttcatttcatttggagaggcactccatttgaatctat

caaaccaaaacacattgagcaaaatggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttcc

ttctcagatcttcgcgacgtcactcctcagccaaaacgacacccccatctgtctatccactggcccctggatctgc

tgcccaaactaactccatggtgaccctgggatgcctggtcaagggctatttccctgagccagtgacagtgacctg

gaactctggatccctgtccagcggtgtgcacaccttcccagctgtcctgcagtctgacctctacactctgagcag

ctcagtgactgtcccctccagcacctggcccagcgagaccgtcacctgcaacgttgcccacccggccagcag

caccaaggtggacaagaaaattgtgcccagggattgtggttgtaagccttgcatatgtacagtcccagaagtatc

atctgtcttcatcttccccccaaagcccaaggatgtgctcaccattactctgactcctaaggtcacgtgtgttgtggt

agacatcagcaaggatgatcccgaggtccagttcagctggtttgtagatgatgtggaggtgcacacagctcaga

cgcaaccccgggaggagcagttcaacagcactttccgctcagtcagtgaacttcccatcatgcaccaggactg

gctcaatggcaaggagacgtccagattttggcgatctattcaactgtcgccagttcattggtactggtagtctccct

gggggcaatcagtttctggatgtgctctaatgggtctctacagtgtagaatatgtatttaaaggccttagtcgtgtc

gtttttcaaataatataatccttttagggttttagttagtttaaattttctgttgctcctgtttagcaggtcgtgccttcagc

aagcacacaaaaacagagtgtttattttaagttgtttgtttagtgattcaaaaaaaaaatcgttcaaacatttggcaat

aaagtttcttaagattgaatcctgttgccggtcttgcgatgattatcatataatttctgttgaattacgttaagcatgta

ataattaacatgtaatgcatgacgttatttatgagatgggtttttatgattagagtcccgcaattatacatttaatacgc

gatagaaaacaaaatatagcgcgcaaactaggataaattatcgcgcgcggtgtcatctatgttactagatctctag

agtctcaagcttggcgcgcccacgtgactagtggcactggccgtcgttttacaacgtcgtgactgggaaaaccc

tggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgca

ccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgctagagcagcttgagcttggatcagattgtc

gtttcccgccttcagtttaaactatcagtgtttgacaggatatattggcgggtaaacctaagagaaaagagcgttta construct 8591 from 2X35S prom to NOS terminator (SEQ ID NO: 36)

GTCAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCAA

AGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACAA

AGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCTG

TCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAAAT

GCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTGCC

GACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGTGG

AAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGATG

TGATAACATGGTGGAGCACGACACACTTGTCTACTCCAAAAATATCA

AAGATACAGTCTCAGAAGACCAAAGGGCAATTGAGACTTTTCAACA

AAGGGTAATATCCGGAAACCTCCTCGGATTCCATTGCCCAGCTATCT

GTCACTTTATTGTGAAGATAGTGGAAAAGGAAGGTGGCTCCTACAA

ATGCCATCATTGCGATAAAGGAAAGGCCATCGTTGAAGATGCCTCTG

CCGACAGTGGTCCCAAAGATGGACCCCCACCCACGAGGAGCATCGT

GGAAAAAGAAGACGTTCCAACCACGTCTTCAAAGCAAGTGGATTGA

TGTGATATCTCCACTGACGTAAGGGATGACGCACAATCCCACTATCC

TTCGCAAGACCCTTCCTCTATATAAGGAAGTTCATTTCATTTGGAGA

GGCACTCCATTTGAATCTATCAAACCAAAACACATTGAGCAAAATG

GCGAAAAACGTTGCGATTTTCGGCTTATTGTTTTCTCTTCTTGTGTTG

GTTCCTTCTCAGATCTTCGCGGTGAATCTTACGACGCGAACACAGTT

ACCACCCGCATATACAAATAGCTTCACTCGGGGTGTTTATTACCCCG

ACAAAGTGTTCAGGTCCTCCGTGCTCCACTCAACACAGGACCTCTTT

CTTCCTTTCTTTTCTAACGTGACATGGTTTCATGCCATTCATGTATCC

GGCACTAACGGTACTAAGAGGTTCGATAATCCTGTGCTCCCTTTCAA

TGACGGCGTTTACTTTGCAAGCACAGAGAAGAGTAACATCATCCGA

GGTTGGATCTTTGGCACTACCCTCGATTCAAAGACGCAGAGCCTCCT

CATTGTGAACAATGCCACTAACGTGGTGATCAAAGTTTGCGAGTTTC

AGTTCTGCAATGACCCTTTCTTGGGGGTGTACTATCATAAGAACAAC

AAGTCTTGGATGGAATCTGAATTCCGCGTCTATAGCAGCGCCAACAA

CTGCACCTTTGAATACGTGTCCCAGCCCTTCCTTATGGACCTGGAGG

GAAAGCAGGGAAACTTTAAGAATCTGAGAGAGTTCGTGTTTAAAAA

TATCGACGGCTATTTTAAGATCTATTCTAAGCACACGCCTATTAATCT

CGTGCGCGATCTTCCACAAGGCTTCAGCGCCCTGGAACCACTCGTGG

ACCTCCCAATTGGTATCAACATCACTAGATTTCAGACTCTGCTTGCC

CTCCACCGATCCTATCTGACACCCGGAGACTCCTCTAGCGGCTGGAC

TGCCGGCGCTGCCGCTTATTACGTTGGTTATCTTCAGCCACGCACGTT

CCTGCTGAAGTATAACGAGAATGGTACTATTACCGATGCCGTGGATT

GTGCCCTTGACCCCCTGTCCGAAACTAAGTGCACACTCAAGTCATTC

ACTGTGGAAAAAGGAATCTACCAGACAAGCAATTTTCGGGTCCAGC

CTACTGAGAGCATTGTGCGCTTTCCTAACATCACAAATCTTTGCCCCT

TCGGAGAGGTTTTCAATGCTACACGGTTTGCCTCCGTGTATGCCTGG

AACCGCAAGAGAATTTCCAATTGCGTGGCCGATTACTCCGTGCTCTA

CAATAGTGCAAGCTTTAGCACCTTTAAGTGCTATGGCGTATCCCCTA

CTAAGCTTAACGACTTGTGTTTCACAAACGTGTATGCCGACTCCTTT

GTGATACGGGGCGACGAAGTTAGACAGATAGCACCAGGACAGACGG

GAAAGATAGCTGACTACAACTATAAGCTTCCTGATGACTTCACTGGC

TGCGTTATCGCGTGGAATTCTAACAACCTGGACTCAAAAGTCGGCGG

CAACTATAACTATCTCTATCGGCTGTTCCGCAAGAGTAACCTTAAGC

CCTTTGAGAGAGATATAAGCACTGAAATCTACCAGGCTGGCAGTAC

GCCCTGTAATGGCGTGGAAGGCTTTAATTGTTATTTTCCACTGCAAT

CCTATGGTTTTCAGCCAACCAATGGCGTGGGCTACCAACCATACCGC

GTCGTGGTGCTCTCCTTTGAACTGCTCCACGCTCCCGCGACTGTCTGC

GGCCCCAAGAAGTCCACGAACCTTGTGAAGAATAAGTGCGTTAATTT

TAATTTCAACGGCCTCACTGGAACAGGAGTGCTCACTGAGAGTAAC

AAGAAGTTCCTGCCATTTCAACAATTTGGCAGAGACATAGCCGATAC

TACTGACGCCGTTAGGGACCCCCAGACCCTCGAGATTCTCGATATAA

CGCCCTGCTCCTTCGGTGGAGTTTCCGTGATCACGCCAGGCACCAAT

ACCAGTAACCAGGTCGCCGTGCTGTATCAGGATGTCAACTGTACTGA

GGTGCCCGTAGCCATCCATGCGGATCAGCTCACACCAACTTGGAGG

GTGTACAGCACCGGCTCCAATGTATTCCAGACTCGGGCCGGATGCCT

TATTGGCGCCGAACACGTGAACAATAGTTACGAATGCGATATTCCAA

TTGGCGCCGGAATCTGTGCTAGCTACCAGACTCAGACGAACTCCCCA

GGCAGCGCCAGCAGCGTTGCCAGCCAGTCAATCATCGCTTATACAAT

GTCACTTGGAGCCGAAAACTCCGTGGCTTACTCAAACAACAGCATCG

CCATCCCCACAAACTTCACCATATCCGTGACAACTGAGATTCTGCCA

GTGTCCATGACTAAGACGTCCGTAGATTGCACTATGTACATATGCGG

CGACAGCACAGAATGTTCTAATCTGCTGCTGCAATATGGAAGCTTCT

GCACTCAACTGAACAGAGCGCTCACAGGCATCGCCGTGGAGCAGGA

TAAGAATACCCAGGAGGTGTTCGCCCAAGTTAAGCAGATCTACAAG

ACCCCACCCATAAAGGATTTCGGTGGATTCAATTTTAGTCAGATACT

CCCAGACCCATCTAAGCCATCCAAGAGGAGCTTTATCGAGGATCTTT

TGTTTAACAAAGTTACTCTGGCCGACGCCGGTTTCATCAAGCAGTAC

GGAGATTGCCTCGGCGACATCGCTGCTCGTGACCTCATCTGTGCGCA

AAAGTTTAACGGTCTGACGGTGCTGCCTCCCCTCCTTACTGATGAAA

TGATCGCCCAGTATACCAGCGCACTCCTCGCTGGCACCATAACATCC

GGTTGGACATTCGGCGCTGGTGCAGCACTGCAGATACCATTCGCCAT

GCAAATGGCATATCGTTTCAACGGTATCGGTGTCACACAGAATGTCC

TATATGAGAACCAGAAGCTGATCGCAAATCAGTTCAATAGTGCCATC

GGAAAAATCCAGGATAGCCTTAGCAGCACAGCCTCAGCCCTTGGCA

AACTCCAGGATGTCGTGAACCAGAATGCCCAGGCTCTCAATACCCTC

GTGAAGCAGCTCTCATCTAATTTCGGCGCAATTTCCAGTGTCCTCAA

CGACATCCTCAGCCGCCTCGACCCCCCCGAGGCCGAAGTGCAGATTG

ACAGACTGATTACAGGTCGACTCCAGAGCCTCCAGACTTACGTGACT

CAGCAGCTGATAAGAGCCGCCGAGATAAGGGCCAGCGCTAACCTGG

CTGCCACAAAGATGTCTGAGTGCGTGCTGGGCCAGTCCAAGAGAGT

AGACTTCTGTGGCAAAGGCTACCATCTGATGAGCTTCCCACAATCCG

CACCTCACGGCGTAGTGTTCCTCCACGTGACATATGTACCGGCTCAG

GAGAAGAATTTCACTACCGCTCCTGCTATATGCCATGATGGAAAGGC

TCACTTCCCCCGGGAGGGGGTGTTCGTGTCCAACGGCACCCATTGGT

TTGTGACTCAGCGGAATTTCTACGAACCCCAGATCATAACCACTGAC

AACACATTTGTGTCCGGAAATTGTGACGTGGTCATTGGAATAGTGAA

CAACACTGTTTATGATCCACTGCAGCCAGAACTTGACAGCTTTAAGG

AGGAGCTCGACAAGTACTTCAAGAATCATACGTCACCAGATGTGGA

CCTCGGAGATATTAGCGGTATCAATGCCAGTGTTGTCAATATTCAGA

AGGAAATAGACCGCCTTAATGAGGTCGCCAAAAATCTGAACGAGAG

CCTCATCGATCTTCAGGAGCTGGGCAAATATGAGCAGTACATCAAGT

GGCCTTGGTATATTTGGCTTGGCTTCATCGCCGGCCTGATCGCCATA

GTAATGGTCACAATTATGCTCTGCTGCATGACCTCTTGCTGCTCCTGT

CTGAAAGGCTGCTGCTCTTGCGGATCCTGCTGCAAATTTGATGAGGA

TGACAGTGAACCAGTCCTGAAGGGCGTGAAGCTGCACTATACTTAG

AGGCCTTAGTCGTGTCGTTTTTCAAATAATATAATCCTTTTAGGGTTT

TAGTTAGTTTAAATTTTCTGTTGCTCCTGTTTAGCAGGTCGTGCCTTC

AGCAAGCACACAAAAACAGAGTGTTTATTTTAAGTTGTTTGTTTAGT

GATTCAAAAAAAAAATCGTTCAAACATTTGGCAATAAAGTTTCTTAA

GATTGAATCCTGTTGCCGGTCTTGCGATGATTATCATATAATTTCTGT

TGAATTACGTTAAGCATGTAATAATTAACATGTAATGCATGACGTTA

TTTATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAA

TACGCGATAGAAAACAAAATATAGCGCGCAAACTAGGATAAATTAT

CGCGCGCGGTGTCATCTATGTTACTAGAT

Modified SARS-CoV-2S protein with H5i hemagglutinin CT C-terminal region, variation 2 (SEQ ID NO: 37)

WYIWLGFIAGLIAIVMVTIMAGLSLWMCSNGSLQCRICI

Modified SARS-CoV-2S protein with H5i hemagglutinin CT, variation 3 (SEQ ID NO: 38)

WYIWLGFIAGLIAIVMVTIMLCCMCSNGSLQCRICI

Modified SARS-CoV-2S protein with H5i hemagglutinin CT, variation 4 (SEQ ID NO: 39)

WYIWLGFIAGLIAIVMVTIMLCCSNGSLQCRICI

3' UTR AvB (Arrachacha Virus B) (SEQ ID NO: 40)

TAGTCGTGTCGTTTTTCAAATAATATAATCCTTTTAGGGTTTTAGTTA

GTTTAAATTTTCTGTTGCTCCTGTTTAGCAGGTCGTGCCTTCAGCAAG

CACACAAAAACAGAGTGTTTATTTTAAGTTGTTTGTTTAGTGATTCA

AAAAAAAA

3' UTR trBNYVV (beet necrotic yellow vein Virus) (SEQ ID NO: 41)

CCTATCTTGATGAAGGTTGTTGTGGTTTTCTCATTACTGTTTTATTAT

TGTTTGAGTTGCTTATGTCGGTTCTTGATTATGTGGTGCATAATTATT

GAACTAATTGTTTGTTGGGTTGTAATGTACTGACTGGGTGTGAATTG

TACCAGTCGTTAAAGGGTTTACTATCAGTATATTGATAT

3' UTR SBMV (southern Bean mosaic Virus) (SEQ ID NO: 42)

TGAGGAGTTGTATAATAATACCTGCACCCTTCTCTTTGGCAGGGAGG

GTGTTTCGTTTTCACAATGCCACGCGCTTGAGGGAGAATGCACGTTA

ATCATCCCTCCGCTAGTGATGGAGCGTAATCCAAAAGT

3' UTR TuRSV (turnip round spot virus) (SEQ ID NO: 43)

TGATTTATAATAGCCATAGATTAAGTTTAAATGTATTACGTTTGTATTTTATTCTCTTTTTTAAGTTTCCTATGTTGTTTTAAATTAAATATCTGTATAATTAGTAGATGTAAATCTGCTTTGTGCGTTTGACAGTCTGTGGAAACGCACTGGTTCATGAGATAGGACCACCTAGGAGGTAGGACTCTGGGTTTTAATTATCTCATTTCTTAGTTATACCGTATTATATATATGATTTAGTAGTAATTGTTTTCTCTTGATATGTATTATTACTTTTTTATT3' UTR CPMV (cowpea mosaic Virus) (SEQ ID NO: 44)

ATTTTCTTTAGTTTGAATTTACTGTTATTCGGTGTGCATTTCTATGTTTGGTGAGCGGTTTTCTGTGCTCAGAGTGTGTTTATTTTATGTAATTTAATTTCTTTGTGAGCTCCTGTTTAGCAGGTCGTCCCTTCAGCAAGGACACAAAAAGATTTTAATTTTATT

3' UTR BBTMV (broad bean eukaryotic mosaic Virus) (SEQ ID NO: 45)

TAGTTTTCTTCCGCTTTTCTTTTGTAGTGTGTGGTTTTCTTTGTTTCTTCTTTTCTTTTCTCTTTCCTTTTCTCTTACTCCTGCCTGGCAGGTCGTGCCTTCAGTAAGCACAACAAAAATATGCATTTATTAGAGTATTTCTTTCTTCTTTAGCATAAAGGTATTGAAGACCTATAAACTTCGTCCGGGTTGGGGAAAGTACCAGCTTAGCATATCTTTAGAAAACTATATAGAGCTCTTTACCTTGAGTTGTTTCCTAAAGTTTATGCAAAAAA

3' UTR treuMV (European melon Virus) (SEQ ID NO: 46)

CTCACGTCTGGGGTGAGCCCTAGCCAAATAGGAAAACGATAAGCGCTTTGCATGCAAAATGAGTTGGGCCACAAGTGCCACTCGCAGCGAAGGCGGTCTGAGGTTTCCCCCTGGCGGTTACTTCCATATCTTTGGGAGATAACTGGG

( PDI) modified SARS-CoV-2S protein gsas+pp, with H5i hemagglutinin CT AA (SEQ ID NO:47 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+4p, having the H5i hemagglutinin CTAA (SEQ ID NO:48 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+6p, having H5i hemagglutinin CT AA (SEQ ID NO:49 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQF

NSAIGKIQDSLSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVL

NDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAAT

KMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKN

FTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVS

GNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGI

NASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFI

AGLIAIVMVTIMLSLWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+pp+923, having H5i hemagglutinin CT AA (SEQ ID NO:50 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSFSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLSLWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+4p+923, having H5i hemagglutinin CT AA (SEQ ID NO:51 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSFSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSV

LNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAAT

KMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKN

FTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVS

GNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGI

NASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFI

AGLIAIVMVTIMLSLWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+6p+923, having H5i hemagglutinin CT AA (SEQ ID NO:52 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSPIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGPALQIPFPMQMAYRFNGIGVTQNVLYENQKLIANQF

NSAIGKIQDSFSSTPSALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVL

NDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAAT

KMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKN

FTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVS

GNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGI

NASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFI

AGLIAIVMVTIMLSLWMCSNGSLQCRICI

(PDI) modified SARS-CoV-2S protein GSAS+PP, having H1 Cal hemagglutinin

CT AA(SEQ ID NO：53)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLSFWMCSNGSLQCRICI

( PDI) modified SARS-CoV-2S protein gsas+pp, with H3 Minn hemagglutinin CT AA (SEQ ID NO:54 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLMWACQKGNIRCNICI

(PDI) modified SARS-CoV-2S protein GSAS+PP, having H6 HK hemagglutinin

CT AA(SEQ ID NO：55)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLGLWMCSNGSMQCRICI

( PDI) modified SARS-CoV-2S protein gsas+pp, with H7 Guangdong hemagglutinin CT AA (SEQ ID NO:56 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLVFICVKNGNMRCTICI

(PDI) modified SARS-CoV-2S protein GSAS+PP, having H9 HK hemagglutinin

CT AA(SEQ ID NO：57)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLLFWAMSNGSCRCNICI

( PDI) modified SARS-CoV-2S protein gsas+pp, with B/Wash hemagglutinin CT AA (SEQ ID NO:58 )

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLVVYMVSRDNVSCSICL

(PDI) modified SARS-CoV-2S protein GSAS+PP with H5i hemagglutinin CT

(alternative 1) AA (SEQ ID NO: 59)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMMAGLSLWMCSNGSLQCRICI

(PDI) modified SARS-CoV-2S protein GSAS+PP with H5i hemagglutinin CT

(alternative 2) AA (SEQ ID NO: 60)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMAGLSLWMCSNGSLQCRICI

(PDI) modified SARS-CoV-2S protein GSAS+PP with H5i hemagglutinin CT

(alternative 3) AA (SEQ ID NO: 61)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQ

FNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISS

VLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLA

ATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQE

KNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTF

VSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDIS

GINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLG

FIAGLIAIVMVTIMLCCMCSNGSLQCRICI

(PDI) modified SARS-CoV-2S protein GSAS+PP with H5i hemagglutinin CT

(alternative 4) AA (SEQ ID NO: 62)

MAKNVAIFGLLFSLLVLVPSQIFAVNLTTRTQLPPAYTNSFTRGVYYPD

KVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDG

VYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDP

FLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNF

KNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR

FQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTI

TDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNL

CPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSP

TKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCV

IAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNG

VEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKS

TNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRD

PQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQ

LTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ

TNSPGSASSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPV

SMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNT

QEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLA

DAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALL

AGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCSNGSLQCRICI

The N-terminal region of the natural SARS-CoV-2S protein (natural signal peptide sequence underlined) (SEQ ID NO: 63)

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNS

Modified TMCT with intermediate peptide sequence (X) n (SEQ ID NO: 64)

WYIWLGFIAGLIAIVMVTIM(X)ncsngsXXCXICI

PDI-S protein GSAS+4P-DNA (SEQ ID NO: 65)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcggtgaatcttacgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttcaggtcctccgtgctccactcaacacaggacctctttcttcctttcttttctaacgtgacatggtttcatgccattcatgtatccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcacagagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtgaacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcataagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtgtcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaatatcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgccctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcctatctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccacgcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccgaaactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctactgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagccccatcgaggatcttttgtttaaca

aagttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctca

tctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccag

cgcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgcca

tgcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaa

atcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacaccctcagcccttggcaaactccag

gatgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttcca

gtgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacagg

tcgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctctttatggatgtgctccaatggatcgttacaatgcagaatttgc

atttaa

PDI-S protein GSAS+6P-DNA (SEQ ID NO: 66)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcggtgaatctt

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

aggtcctccgtgctccactcaacacaggacctctttcttcctttcttttctaacgtgacatggtttcatgccattcatgt

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagccccatcgaggatcttttgtttaaca

aagttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctca

tctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccag

cgcactcctcgctggcaccataacatccggttggacattcggcgctggtcccgcactgcagataccattccccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacaccctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctctttatggatgtgctccaatggatcgttacaatgcagaatttgc

atttaa

PDI-S protein GSAS+2P+L923F-DNA (SEQ ID NO: 67)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagcttcagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctctttatggatgtgctccaatggatcgttacaatgcagaatttgc

atttaa

PDI-S protein GSAS+4P+L923F-DNA (SEQ ID NO: 68)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagccccatcgaggatcttttgtttaaca

aagttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctca

tctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccag

cgcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgcca

tgcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaa

atcagttcaatagtgccatcggaaaaatccaggatagcttcagcagcacaccctcagcccttggcaaactccag

gatgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttcca

gtgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacagg

tcgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctctttatggatgtgctccaatggatcgttacaatgcagaatttgc

atttaa

PDI-S protein GSAS+6P+L923F-DNA (SEQ ID NO: 69)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagccccatcgaggatcttttgtttaaca

aagttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctca

tctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccag

cgcactcctcgctggcaccataacatccggttggacattcggcgctggtcccgcactgcagataccattccccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagcttcagcagcacaccctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctctttatggatgtgctccaatggatcgttacaatgcagaatttgc

atttaa

PDI-modified S protein with H5i hemagglutinin CT (V1) DNA (SEQ ID NO: 70)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgatggccggcctctctttatggatgtgctccaatggatcgttacaatg

cagaatttgcatttaa

PDI-modified S protein with H5i hemagglutinin CT (V2) DNA (SEQ ID NO: 71)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatggccggcctctctttatggatgtgctccaatggatcgttacaatgcag

aatttgcatttaa

PDI-modified S protein with H5i hemagglutinin CT (V3) DNA (SEQ ID NO: 72)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctgctgcatgtgctccaatggatcgttacaatgcagaatttgcatt

taa

PDI-modified S protein with H5i hemagglutinin CT (V4) DNA (SEQ ID NO: 73)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctctgctgctccaatggatcgttacaatgcagaatttgcatttaa

PDI-S protein+H2 CalDNA (SEQ ID NO: 74)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcagcttctggatgtgctctaatgggtctctacagtgtagaatatgt

atttaa

PDI-S protein+H23 Minn DNA (SEQ ID NO: 75)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcatgtgggcctgtcagaagggcaacatcagatgcaacatctgc

atctaa

PDI-S protein+H2HKDNA (SEQ ID NO: 76)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcggtctttggatgtgttcaaatggttcaatgcagtgcaggatatgt

atataa

PDI-S protein+H27 Guangdong DNA (SEQ ID NO: 77)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcgtcttcatatgtgtgaagaatggaaacatgcggtgcactatttgt

atataa

PDI-S protein+H2HKDNA (SEQ ID NO: 78)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcctgttctgggccatgtccaatggatcttgcagatgcaacatttgt

atataa

PDI-S protein+B/Wash DNA (SEQ ID NO: 79)

acgacgcgaacacagttaccacccgcatatacaaatagcttcactcggggtgtttattaccccgacaaagtgttc

atccggcactaacggtactaagaggttcgataatcctgtgctccctttcaatgacggcgtttactttgcaagcaca

gagaagagtaacatcatccgaggttggatctttggcactaccctcgattcaaagacgcagagcctcctcattgtg

aacaatgccactaacgtggtgatcaaagtttgcgagtttcagttctgcaatgaccctttcttgggggtgtactatcat

aagaacaacaagtcttggatggaatctgaattccgcgtctatagcagcgccaacaactgcacctttgaatacgtg

tcccagcccttccttatggacctggagggaaagcagggaaactttaagaatctgagagagttcgtgtttaaaaat

atcgacggctattttaagatctattctaagcacacgcctattaatctcgtgcgcgatcttccacaaggcttcagcgc

cctggaaccactcgtggacctcccaattggtatcaacatcactagatttcagactctgcttgccctccaccgatcct

atctgacacccggagactcctctagcggctggactgccggcgctgccgcttattacgttggttatcttcagccac

gcacgttcctgctgaagtataacgagaatggtactattaccgatgccgtggattgtgcccttgaccccctgtccga

aactaagtgcacactcaagtcattcactgtggaaaaaggaatctaccagacaagcaattttcgggtccagcctac

tgagagcattgtgcgctttcctaacatcacaaatctttgccccttcggagaggttttcaatgctacacggtttgcctc

cgtgtatgcctggaaccgcaagagaatttccaattgcgtggccgattactccgtgctctacaatagtgcaagcttt

agcacctttaagtgctatggcgtatcccctactaagcttaacgacttgtgtttcacaaacgtgtatgccgactccttt

gtgatacggggcgacgaagttagacagatagcaccaggacagacgggaaagatagctgactacaactataag

cttcctgatgacttcactggctgcgttatcgcgtggaattctaacaacctggactcaaaagtcggcggcaactata

actatctctatcggctgttccgcaagagtaaccttaagccctttgagagagatataagcactgaaatctaccaggc

tggcagtacgccctgtaatggcgtggaaggctttaattgttattttccactgcaatcctatggttttcagccaaccaa

tggcgtgggctaccaaccataccgcgtcgtggtgctctcctttgaactgctccacgctcccgcgactgtctgcgg

ccccaagaagtccacgaaccttgtgaagaataagtgcgttaattttaatttcaacggcctcactggaacaggagt

gctcactgagagtaacaagaagttcctgccatttcaacaatttggcagagacatagccgatactactgacgccgt

tagggacccccagaccctcgagattctcgatataacgccctgctccttcggtggagtttccgtgatcacgccagg

caccaataccagtaaccaggtcgccgtgctgtatcaggatgtcaactgtactgaggtgcccgtagccatccatg

cggatcagctcacaccaacttggagggtgtacagcaccggctccaatgtattccagactcgggccggatgcctt

attggcgccgaacacgtgaacaatagttacgaatgcgatattccaattggcgccggaatctgtgctagctaccag

actcagacgaactccccaggcagcgccagcagcgttgccagccagtcaatcatcgcttatacaatgtcacttgg

agccgaaaactccgtggcttactcaaacaacagcatcgccatccccacaaacttcaccatatccgtgacaactg

agattctgccagtgtccatgactaagacgtccgtagattgcactatgtacatatgcggcgacagcacagaatgtt

ctaatctgctgctgcaatatggaagcttctgcactcaactgaacagagcgctcacaggcatcgccgtggagcag

gataagaatacccaggaggtgttcgcccaagttaagcagatctacaagaccccacccataaaggatttcggtgg

attcaattttagtcagatactcccagacccatctaagccatccaagaggagctttatcgaggatcttttgtttaacaa

agttactctggccgacgccggtttcatcaagcagtacggagattgcctcggcgacatcgctgctcgtgacctcat

ctgtgcgcaaaagtttaacggtctgacggtgctgcctcccctccttactgatgaaatgatcgcccagtataccagc

gcactcctcgctggcaccataacatccggttggacattcggcgctggtgcagcactgcagataccattcgccat

gcaaatggcatatcgtttcaacggtatcggtgtcacacagaatgtcctatatgagaaccagaagctgatcgcaaa

tcagttcaatagtgccatcggaaaaatccaggatagccttagcagcacagcctcagcccttggcaaactccagg

atgtcgtgaaccagaatgcccaggctctcaataccctcgtgaagcagctctcatctaatttcggcgcaatttccag

tgtcctcaacgacatcctcagccgcctcgacccccccgaggccgaagtgcagattgacagactgattacaggt

cgactccagagcctccagacttacgtgactcagcagctgataagagccgccgagataagggccagcgctaac

ctggctgccacaaagatgtctgagtgcgtgctgggccagtccaagagagtagacttctgtggcaaaggctacc

atctgatgagcttcccacaatccgcacctcacggcgtagtgttcctccacgtgacatatgtaccggctcaggaga

agaatttcactaccgctcctgctatatgccatgatggaaaggctcacttcccccgggagggggtgttcgtgtcca

acggcacccattggtttgtgactcagcggaatttctacgaaccccagatcataaccactgacaacacatttgtgtc

cggaaattgtgacgtggtcattggaatagtgaacaacactgtttatgatccactgcagccagaacttgacagcttt

aaggaggagctcgacaagtacttcaagaatcatacgtcaccagatgtggacctcggagatattagcggtatcaa

tgccagtgttgtcaatattcagaaggaaatagaccgccttaatgaggtcgccaaaaatctgaacgagagcctcat

cgatcttcaggagctgggcaaatatgagcagtacatcaagtggccttggtatatttggcttggcttcatcgccggc

ctgatcgccatagtaatggtcacaattatgctcgttgtttatatggtctccagagacaatgtttcttgctccatttgtct

ataa

IF-H1HawaiiCT.r(SEQ ID NO：80)

acgacacgactaaggcctttaaatacatattctacactgtagagaccc

IF-H3MinnesotaCT.r(SEQ ID NO：81)

acgacacgactaaggcctttagatgcagatgttgcatctgatgttgcccttctg

IF-HongKongCT.r(SEQ ID NO：82)

acgacacgactaaggcctttatatacatatcctgcactgcattgaaccattt

IF-GuangdongCT.r(SEQ ID NO：83)

acgacacgactaaggcctttatatacaaatagtgcaccgcatgtttcca

IF-H9HKCT.r(SEQ ID NO：84)

acgacacgactaaggcctttatatacaaatgttgcatctgcaagatccat

IF-BWashCT.r(SEQ ID NO：85)

acgacacgactaaggcctttatagacaaatggagcaagaaacattgtctc

IF(nbHEL40)-PDI.c(SEQ ID NO：86)

ccaaaacacattgagcaaaatggcgaaaaacgttgcgattttcggcttat

IF(AvB+wtCT).r(SEQ ID NO：87)

ACGACACGACTAAGGCCTTTAGGTATAATGGAGTTTCACCCCCTTCA

GAA

PDI-SARS-COV-1 wtTMCT-DNA(SEQ ID NO：88)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTCCGA

TCTGGATCGGTGCACTACATTTGACGATGTGCAGGCACCTAATTATA

CTCAGCACACCTCTTCCATGCGGGGCGTGTACTACCCCGACGAGATT

TTTAGAAGTGACACACTGTACCTGACCCAAGACCTTTTTCTCCCATTT

TATAGCAATGTCACGGGATTCCACACTATCAATCACACATTCGGAAA

CCCTGTTATCCCCTTTAAAGACGGTATCTACTTTGCTGCTACTGAGAA

ATCGAATGTTGTTCGCGGTTGGGTGTTCGGCTCAACCATGAACAACA

AGAGTCAGTCAGTAATAATTATAAACAACTCAACCAATGTCGTCATC

AGGGCTTGCAACTTCGAGCTCTGCGATAACCCCTTCTTTGCGGTGTC

CAAACCGATGGGCACTCAGACCCATACCATGATTTTTGACAATGCCT

TTAATTGTACTTTCGAATACATCAGCGATGCCTTCTCGCTGGATGTGT

CCGAGAAGAGCGGTAACTTCAAGCATTTGCGGGAGTTCGTTTTCAAA

AACAAAGACGGGTTTTTGTATGTCTACAAAGGCTATCAGCCCATTGA

TGTGGTCAGGGATCTGCCCAGTGGTTTCAACACACTGAAGCCCATCT

TCAAGTTGCCACTCGGCATCAACATCACTAATTTCCGCGCCATCCTA

ACTGCTTTTTCGCCAGCGCAGGATATTTGGGGGACATCCGCCGCAGC

TTACTTCGTGGGATATCTGAAGCCCACCACTTTTATGCTAAAGTACG

ACGAGAATGGCACCATCACCGATGCCGTGGACTGCTCACAGAATCC

TCTCGCAGAGCTCAAGTGTTCAGTGAAGTCATTTGAGATCGACAAAG

GGATCTACCAAACATCTAACTTTCGCGTCGTGCCTTCCGGTGACGTA

GTCCGTTTCCCAAATATCACTAACTTGTGCCCTTTTGGTGAAGTATTC

AACGCAACCAAATTCCCCAGTGTGTATGCGTGGGAGCGCAAAAAGA

TCAGTAACTGTGTGGCTGACTATAGTGTTCTGTACAATAGCACCTTC

TTCAGCACCTTCAAGTGTTATGGAGTGAGCGCTACAAAACTGAACGA

TCTTTGTTTCTCAAACGTGTACGCCGATTCATTTGTCGTTAAAGGTGA

CGATGTGAGGCAGATCGCTCCAGGCCAGACAGGTGTGATTGCTGAC

TATAATTACAAACTGCCAGACGACTTCATGGGGTGCGTGCTAGCTTG

GAATACAAGAAACATTGACGCCACCTCCACGGGAAATTACAATTAC

AAGTATCGTTACCTTCGCCATGGAAAGTTGAGACCCTTCGAGCGTGA

TATAAGTAACGTGCCCTTTAGTCCAGATGGAAAACCCTGCACACCCC

CTGCTCTCAATTGCTATTGGCCTCTCAATGACTACGGCTTTTACACAA

CTACTGGCATCGGATACCAGCCTTACCGGGTCGTGGTGCTCAGTTTT

GAGTTGCTTAACGCACCCGCCACCGTGTGTGGTCCTAAACTTTCTAC

TGACCTGATTAAAAACCAATGCGTCAACTTCAATTTTAACGGGCTGA

CCGGCACCGGTGTCCTGACCCCTAGCTCTAAGAGATTCCAGCCTTTT

CAGCAGTTCGGGAGGGATGTGAGCGACTTTACCGACTCTGTCAGGG

ATCCAAAGACCAGCGAGATACTGGATATCTCGCCCTGCAGTTTCGGT

GGCGTGTCCGTTATTACACCTGGCACCAACGCCTCCTCAGAGGTGGC

GGTGCTCTATCAAGATGTCAACTGCACTGATGTGTCAACTGCCATCC

ATGCCGATCAGCTGACCCCCGCCTGGCGCATCTACAGTACCGGGAAC

AACGTTTTTCAGACCCAGGCCGGCTGTCTAATCGGCGCAGAGCACGT

TGACACATCCTACGAATGTGACATACCTATCGGGGCAGGCATTTGCG

CTAGCTACCATACCGTGTCACTGTTGGCTTCCACGTCACAAAAGTCA

ATCGTTGCCTACACGATGAGTCTGGGGGCTGACTCATCTATCGCCTA

CAGCAACAATACCATTGCAATTCCCACAAACTTCAGTATCTCCATCA

CAACAGAGGTGATGCCCGTTTCTATGGCTAAAACATCAGTCGATTGC

AATATGTATATATGCGGCGATAGTACTGAGTGCGCCAATCTCTTGTT

ACAGTACGGCTCCTTTTGTACCCAGCTGAACCGAGCACTGTCTGGAA

TCGCCGCAGAACAGGATCGCAATACCCGGGAAGTCTTCGCCCAGGT

GAAGCAGATGTACAAAACGCCCACTCTCAAGTATTTCGGCGGATTCA

ACTTTTCTCAGATTTTGCCTGACCCGCTCAAGCCAACAAAACGATCT

TTTATCGAAGACCTTCTGTTTAACAAGGTCACACTGGCGGATGCTGG

GTTCATGAAACAGTACGGTGAATGCCTGGGGGACATCAATGCCAGA

GATCTGATCTGCGCCCAGAAATTCAATGGCTTAACAGTCCTCCCACC

TCTCTTGACCGACGATATGATCGCTGCGTACACCGCTGCTCTGGTAT

CGGGCACCGCGACTGCTGGCTGGACCTTTGGTGCCGGAGCCGCACTC

CAGATCCCATTCGCCATGCAGATGGCCTACCGCTTCAACGGAATCGG

GGTCACCCAGAACGTGCTGTATGAGAACCAGAAACAGATCGCCAAT

CAGTTCAATAAGGCAATTAGTCAGATTCAGGAGAGTCTTACCACTAC

CAGCACCGCCCTGGGCAAGCTGCAAGATGTTGTGAACCAGAATGCG

CAGGCATTAAACACTCTGGTTAAACAGCTGAGCTCAAATTTTGGTGC

AATCTCTTCAGTTCTGAACGATATCCTGAGTCGGCTGGATCCGCCAG

AGGCTGAAGTGCAAATTGATCGTTTGATCACCGGGAGGCTACAATCT

CTGCAGACGTACGTGACCCAGCAGCTCATCCGGGCAGCCGAAATTC

GCGCATCAGCCAACCTCGCTGCAACTAAGATGTCTGAGTGCGTGCTG

GGCCAGAGTAAGAGGGTGGACTTTTGTGGTAAGGGATACCACCTCA

TGTCCTTTCCGCAAGCGGCTCCCCACGGCGTGGTTTTCTTACACGTTA

CCTATGTGCCATCCCAAGAACGCAATTTCACCACCGCTCCAGCTATC

TGTCATGAGGGCAAAGCATATTTCCCCAGGGAAGGAGTATTTGTGTT

TAATGGCACGTCCTGGTTTATAACCCAACGTAACTTTTTCTCCCCACA

GATTATCACAACCGACAACACATTCGTGTCTGGGAATTGTGACGTCG

TGATCGGGATCATTAACAATACCGTTTACGATCCCTTGCAGCCCGAG

CTTGACTCCTTTAAAGAGGAACTAGACAAATACTTTAAGAATCACAC

CTCACCGGACGTAGATTTGGGAGACATCTCTGGAATTAATGCCTCTG

TGGTGAATATCCAGAAGGAGATCGACCGCCTGAATGAAGTCGCCAA

GAACCTCAACGAGTCCCTGATAGATCTGCAAGAACTGGGCAAATAT

GAACAGTACATCAAATGGCCGTGGTACGTGTGGTTGGGCTTTATCGC

TGGACTTATTGCAATCGTGATGGTGACGATTCTGCTCTGCTGTATGA

CTTCCTGCTGCTCTTGTCTGAAGGGCGCCTGTAGCTGTGGTTCCTGCT

GCAAGTTCGACGAAGACGACTCCGAACCAGTTCTGAAGGGGGTGAA

ACTCCATTATACCTAA

PDI-SARS-COV-1 H5iTMCT-DNA(SEQ ID NO：89)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTCCGA

TCTGGATCGGTGCACTACATTTGACGATGTGCAGGCACCTAATTATA

CTCAGCACACCTCTTCCATGCGGGGCGTGTACTACCCCGACGAGATT

TTTAGAAGTGACACACTGTACCTGACCCAAGACCTTTTTCTCCCATTT

TATAGCAATGTCACGGGATTCCACACTATCAATCACACATTCGGAAA

CCCTGTTATCCCCTTTAAAGACGGTATCTACTTTGCTGCTACTGAGAA

ATCGAATGTTGTTCGCGGTTGGGTGTTCGGCTCAACCATGAACAACA

AGAGTCAGTCAGTAATAATTATAAACAACTCAACCAATGTCGTCATC

AGGGCTTGCAACTTCGAGCTCTGCGATAACCCCTTCTTTGCGGTGTC

CAAACCGATGGGCACTCAGACCCATACCATGATTTTTGACAATGCCT

TTAATTGTACTTTCGAATACATCAGCGATGCCTTCTCGCTGGATGTGT

CCGAGAAGAGCGGTAACTTCAAGCATTTGCGGGAGTTCGTTTTCAAA

AACAAAGACGGGTTTTTGTATGTCTACAAAGGCTATCAGCCCATTGA

TGTGGTCAGGGATCTGCCCAGTGGTTTCAACACACTGAAGCCCATCT

TCAAGTTGCCACTCGGCATCAACATCACTAATTTCCGCGCCATCCTA

ACTGCTTTTTCGCCAGCGCAGGATATTTGGGGGACATCCGCCGCAGC

TTACTTCGTGGGATATCTGAAGCCCACCACTTTTATGCTAAAGTACG

ACGAGAATGGCACCATCACCGATGCCGTGGACTGCTCACAGAATCC

TCTCGCAGAGCTCAAGTGTTCAGTGAAGTCATTTGAGATCGACAAAG

GGATCTACCAAACATCTAACTTTCGCGTCGTGCCTTCCGGTGACGTA

GTCCGTTTCCCAAATATCACTAACTTGTGCCCTTTTGGTGAAGTATTC

AACGCAACCAAATTCCCCAGTGTGTATGCGTGGGAGCGCAAAAAGA

TCAGTAACTGTGTGGCTGACTATAGTGTTCTGTACAATAGCACCTTC

TTCAGCACCTTCAAGTGTTATGGAGTGAGCGCTACAAAACTGAACGA

TCTTTGTTTCTCAAACGTGTACGCCGATTCATTTGTCGTTAAAGGTGA

CGATGTGAGGCAGATCGCTCCAGGCCAGACAGGTGTGATTGCTGAC

TATAATTACAAACTGCCAGACGACTTCATGGGGTGCGTGCTAGCTTG

GAATACAAGAAACATTGACGCCACCTCCACGGGAAATTACAATTAC

AAGTATCGTTACCTTCGCCATGGAAAGTTGAGACCCTTCGAGCGTGA

TATAAGTAACGTGCCCTTTAGTCCAGATGGAAAACCCTGCACACCCC

CTGCTCTCAATTGCTATTGGCCTCTCAATGACTACGGCTTTTACACAA

CTACTGGCATCGGATACCAGCCTTACCGGGTCGTGGTGCTCAGTTTT

GAGTTGCTTAACGCACCCGCCACCGTGTGTGGTCCTAAACTTTCTAC

TGACCTGATTAAAAACCAATGCGTCAACTTCAATTTTAACGGGCTGA

CCGGCACCGGTGTCCTGACCCCTAGCTCTAAGAGATTCCAGCCTTTT

CAGCAGTTCGGGAGGGATGTGAGCGACTTTACCGACTCTGTCAGGG

ATCCAAAGACCAGCGAGATACTGGATATCTCGCCCTGCAGTTTCGGT

GGCGTGTCCGTTATTACACCTGGCACCAACGCCTCCTCAGAGGTGGC

GGTGCTCTATCAAGATGTCAACTGCACTGATGTGTCAACTGCCATCC

ATGCCGATCAGCTGACCCCCGCCTGGCGCATCTACAGTACCGGGAAC

AACGTTTTTCAGACCCAGGCCGGCTGTCTAATCGGCGCAGAGCACGT

TGACACATCCTACGAATGTGACATACCTATCGGGGCAGGCATTTGCG

CTAGCTACCATACCGTGTCACTGTTGGCTTCCACGTCACAAAAGTCA

ATCGTTGCCTACACGATGAGTCTGGGGGCTGACTCATCTATCGCCTA

CAGCAACAATACCATTGCAATTCCCACAAACTTCAGTATCTCCATCA

CAACAGAGGTGATGCCCGTTTCTATGGCTAAAACATCAGTCGATTGC

AATATGTATATATGCGGCGATAGTACTGAGTGCGCCAATCTCTTGTT

ACAGTACGGCTCCTTTTGTACCCAGCTGAACCGAGCACTGTCTGGAA

TCGCCGCAGAACAGGATCGCAATACCCGGGAAGTCTTCGCCCAGGT

GAAGCAGATGTACAAAACGCCCACTCTCAAGTATTTCGGCGGATTCA

ACTTTTCTCAGATTTTGCCTGACCCGCTCAAGCCAACAAAACGATCT

TTTATCGAAGACCTTCTGTTTAACAAGGTCACACTGGCGGATGCTGG

GTTCATGAAACAGTACGGTGAATGCCTGGGGGACATCAATGCCAGA

GATCTGATCTGCGCCCAGAAATTCAATGGCTTAACAGTCCTCCCACC

TCTCTTGACCGACGATATGATCGCTGCGTACACCGCTGCTCTGGTAT

CGGGCACCGCGACTGCTGGCTGGACCTTTGGTGCCGGAGCCGCACTC

CAGATCCCATTCGCCATGCAGATGGCCTACCGCTTCAACGGAATCGG

GGTCACCCAGAACGTGCTGTATGAGAACCAGAAACAGATCGCCAAT

CAGTTCAATAAGGCAATTAGTCAGATTCAGGAGAGTCTTACCACTAC

CAGCACCGCCCTGGGCAAGCTGCAAGATGTTGTGAACCAGAATGCG

CAGGCATTAAACACTCTGGTTAAACAGCTGAGCTCAAATTTTGGTGC

AATCTCTTCAGTTCTGAACGATATCCTGAGTCGGCTGGATCCGCCAG

AGGCTGAAGTGCAAATTGATCGTTTGATCACCGGGAGGCTACAATCT

CTGCAGACGTACGTGACCCAGCAGCTCATCCGGGCAGCCGAAATTC

GCGCATCAGCCAACCTCGCTGCAACTAAGATGTCTGAGTGCGTGCTG

GGCCAGAGTAAGAGGGTGGACTTTTGTGGTAAGGGATACCACCTCA

TGTCCTTTCCGCAAGCGGCTCCCCACGGCGTGGTTTTCTTACACGTTA

CCTATGTGCCATCCCAAGAACGCAATTTCACCACCGCTCCAGCTATC

TGTCATGAGGGCAAAGCATATTTCCCCAGGGAAGGAGTATTTGTGTT

TAATGGCACGTCCTGGTTTATAACCCAACGTAACTTTTTCTCCCCACA

GATTATCACAACCGACAACACATTCGTGTCTGGGAATTGTGACGTCG

TGATCGGGATCATTAACAATACCGTTTACGATCCCTTGCAGCCCGAG

CTTGACTCCTTTAAAGAGGAACTAGACAAATACTTTAAGAATCACAC

CTCACCGGACGTAGATTTGGGAGACATCTCTGGAATTAATGCCTCTG

TGGTGAATATCCAGAAGGAGATCGACCGCCTGAATGAAGTCGCCAA

GAACCTCAACGAGTCCCTGATAGATCTGCAAGAACTGGGCAAATAT

GAACAGTACATCAAATGGCCGTGGTACcaaatactgtcaatttattcaacagtggcgag

ttccctagcactggcaatcatgatggctggtctatctttatggatgtgctccaatggatcgttacaatgcagaatttg

cattTAA

PDI-SARS-COV-1 H5iCT-DNA(SEQ ID NO：90)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTCCGA

TCTGGATCGGTGCACTACATTTGACGATGTGCAGGCACCTAATTATA

CTCAGCACACCTCTTCCATGCGGGGCGTGTACTACCCCGACGAGATT

TTTAGAAGTGACACACTGTACCTGACCCAAGACCTTTTTCTCCCATTT

TATAGCAATGTCACGGGATTCCACACTATCAATCACACATTCGGAAA

CCCTGTTATCCCCTTTAAAGACGGTATCTACTTTGCTGCTACTGAGAA

ATCGAATGTTGTTCGCGGTTGGGTGTTCGGCTCAACCATGAACAACA

AGAGTCAGTCAGTAATAATTATAAACAACTCAACCAATGTCGTCATC

AGGGCTTGCAACTTCGAGCTCTGCGATAACCCCTTCTTTGCGGTGTC

CAAACCGATGGGCACTCAGACCCATACCATGATTTTTGACAATGCCT

TTAATTGTACTTTCGAATACATCAGCGATGCCTTCTCGCTGGATGTGT

CCGAGAAGAGCGGTAACTTCAAGCATTTGCGGGAGTTCGTTTTCAAA

AACAAAGACGGGTTTTTGTATGTCTACAAAGGCTATCAGCCCATTGA

TGTGGTCAGGGATCTGCCCAGTGGTTTCAACACACTGAAGCCCATCT

TCAAGTTGCCACTCGGCATCAACATCACTAATTTCCGCGCCATCCTA

ACTGCTTTTTCGCCAGCGCAGGATATTTGGGGGACATCCGCCGCAGC

TTACTTCGTGGGATATCTGAAGCCCACCACTTTTATGCTAAAGTACG

ACGAGAATGGCACCATCACCGATGCCGTGGACTGCTCACAGAATCC

TCTCGCAGAGCTCAAGTGTTCAGTGAAGTCATTTGAGATCGACAAAG

GGATCTACCAAACATCTAACTTTCGCGTCGTGCCTTCCGGTGACGTA

GTCCGTTTCCCAAATATCACTAACTTGTGCCCTTTTGGTGAAGTATTC

AACGCAACCAAATTCCCCAGTGTGTATGCGTGGGAGCGCAAAAAGA

TCAGTAACTGTGTGGCTGACTATAGTGTTCTGTACAATAGCACCTTC

TTCAGCACCTTCAAGTGTTATGGAGTGAGCGCTACAAAACTGAACGA

TCTTTGTTTCTCAAACGTGTACGCCGATTCATTTGTCGTTAAAGGTGA

CGATGTGAGGCAGATCGCTCCAGGCCAGACAGGTGTGATTGCTGAC

TATAATTACAAACTGCCAGACGACTTCATGGGGTGCGTGCTAGCTTG

GAATACAAGAAACATTGACGCCACCTCCACGGGAAATTACAATTAC

AAGTATCGTTACCTTCGCCATGGAAAGTTGAGACCCTTCGAGCGTGA

TATAAGTAACGTGCCCTTTAGTCCAGATGGAAAACCCTGCACACCCC

CTGCTCTCAATTGCTATTGGCCTCTCAATGACTACGGCTTTTACACAA

CTACTGGCATCGGATACCAGCCTTACCGGGTCGTGGTGCTCAGTTTT

GAGTTGCTTAACGCACCCGCCACCGTGTGTGGTCCTAAACTTTCTAC

TGACCTGATTAAAAACCAATGCGTCAACTTCAATTTTAACGGGCTGA

CCGGCACCGGTGTCCTGACCCCTAGCTCTAAGAGATTCCAGCCTTTT

CAGCAGTTCGGGAGGGATGTGAGCGACTTTACCGACTCTGTCAGGG

ATCCAAAGACCAGCGAGATACTGGATATCTCGCCCTGCAGTTTCGGT

GGCGTGTCCGTTATTACACCTGGCACCAACGCCTCCTCAGAGGTGGC

GGTGCTCTATCAAGATGTCAACTGCACTGATGTGTCAACTGCCATCC

ATGCCGATCAGCTGACCCCCGCCTGGCGCATCTACAGTACCGGGAAC

AACGTTTTTCAGACCCAGGCCGGCTGTCTAATCGGCGCAGAGCACGT

TGACACATCCTACGAATGTGACATACCTATCGGGGCAGGCATTTGCG

CTAGCTACCATACCGTGTCACTGTTGGCTTCCACGTCACAAAAGTCA

ATCGTTGCCTACACGATGAGTCTGGGGGCTGACTCATCTATCGCCTA

CAGCAACAATACCATTGCAATTCCCACAAACTTCAGTATCTCCATCA

CAACAGAGGTGATGCCCGTTTCTATGGCTAAAACATCAGTCGATTGC

AATATGTATATATGCGGCGATAGTACTGAGTGCGCCAATCTCTTGTT

ACAGTACGGCTCCTTTTGTACCCAGCTGAACCGAGCACTGTCTGGAA

TCGCCGCAGAACAGGATCGCAATACCCGGGAAGTCTTCGCCCAGGT

GAAGCAGATGTACAAAACGCCCACTCTCAAGTATTTCGGCGGATTCA

ACTTTTCTCAGATTTTGCCTGACCCGCTCAAGCCAACAAAACGATCT

TTTATCGAAGACCTTCTGTTTAACAAGGTCACACTGGCGGATGCTGG

GTTCATGAAACAGTACGGTGAATGCCTGGGGGACATCAATGCCAGA

GATCTGATCTGCGCCCAGAAATTCAATGGCTTAACAGTCCTCCCACC

TCTCTTGACCGACGATATGATCGCTGCGTACACCGCTGCTCTGGTAT

CGGGCACCGCGACTGCTGGCTGGACCTTTGGTGCCGGAGCCGCACTC

CAGATCCCATTCGCCATGCAGATGGCCTACCGCTTCAACGGAATCGG

GGTCACCCAGAACGTGCTGTATGAGAACCAGAAACAGATCGCCAAT

CAGTTCAATAAGGCAATTAGTCAGATTCAGGAGAGTCTTACCACTAC

CAGCACCGCCCTGGGCAAGCTGCAAGATGTTGTGAACCAGAATGCG

CAGGCATTAAACACTCTGGTTAAACAGCTGAGCTCAAATTTTGGTGC

AATCTCTTCAGTTCTGAACGATATCCTGAGTCGGCTGGATCCGCCAG

AGGCTGAAGTGCAAATTGATCGTTTGATCACCGGGAGGCTACAATCT

CTGCAGACGTACGTGACCCAGCAGCTCATCCGGGCAGCCGAAATTC

GCGCATCAGCCAACCTCGCTGCAACTAAGATGTCTGAGTGCGTGCTG

GGCCAGAGTAAGAGGGTGGACTTTTGTGGTAAGGGATACCACCTCA

TGTCCTTTCCGCAAGCGGCTCCCCACGGCGTGGTTTTCTTACACGTTA

CCTATGTGCCATCCCAAGAACGCAATTTCACCACCGCTCCAGCTATC

TGTCATGAGGGCAAAGCATATTTCCCCAGGGAAGGAGTATTTGTGTT

TAATGGCACGTCCTGGTTTATAACCCAACGTAACTTTTTCTCCCCACA

GATTATCACAACCGACAACACATTCGTGTCTGGGAATTGTGACGTCG

TGATCGGGATCATTAACAATACCGTTTACGATCCCTTGCAGCCCGAG

CTTGACTCCTTTAAAGAGGAACTAGACAAATACTTTAAGAATCACAC

CTCACCGGACGTAGATTTGGGAGACATCTCTGGAATTAATGCCTCTG

TGGTGAATATCCAGAAGGAGATCGACCGCCTGAATGAAGTCGCCAA

GAACCTCAACGAGTCCCTGATAGATCTGCAAGAACTGGGCAAATAT

GAACAGTACATCAAATGGCCGTGGTACGTGTGGTTGGGCTTTATCGC

TGGACTTATTGCAATCGTGATGGTGACGATTCTGCTCtctttatggatgtgctcc

aatggatcgttacaatgcagaatttgcattTAA

PDI-SARS-COV-1 H5iCT(V4)-DNA(SEQ ID NO：91)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTCCGA

TCTGGATCGGTGCACTACATTTGACGATGTGCAGGCACCTAATTATA

CTCAGCACACCTCTTCCATGCGGGGCGTGTACTACCCCGACGAGATT

TTTAGAAGTGACACACTGTACCTGACCCAAGACCTTTTTCTCCCATTT

TATAGCAATGTCACGGGATTCCACACTATCAATCACACATTCGGAAA

CCCTGTTATCCCCTTTAAAGACGGTATCTACTTTGCTGCTACTGAGAA

ATCGAATGTTGTTCGCGGTTGGGTGTTCGGCTCAACCATGAACAACA

AGAGTCAGTCAGTAATAATTATAAACAACTCAACCAATGTCGTCATC

AGGGCTTGCAACTTCGAGCTCTGCGATAACCCCTTCTTTGCGGTGTC

CAAACCGATGGGCACTCAGACCCATACCATGATTTTTGACAATGCCT

TTAATTGTACTTTCGAATACATCAGCGATGCCTTCTCGCTGGATGTGT

CCGAGAAGAGCGGTAACTTCAAGCATTTGCGGGAGTTCGTTTTCAAA

AACAAAGACGGGTTTTTGTATGTCTACAAAGGCTATCAGCCCATTGA

TGTGGTCAGGGATCTGCCCAGTGGTTTCAACACACTGAAGCCCATCT

TCAAGTTGCCACTCGGCATCAACATCACTAATTTCCGCGCCATCCTA

ACTGCTTTTTCGCCAGCGCAGGATATTTGGGGGACATCCGCCGCAGC

TTACTTCGTGGGATATCTGAAGCCCACCACTTTTATGCTAAAGTACG

ACGAGAATGGCACCATCACCGATGCCGTGGACTGCTCACAGAATCC

TCTCGCAGAGCTCAAGTGTTCAGTGAAGTCATTTGAGATCGACAAAG

GGATCTACCAAACATCTAACTTTCGCGTCGTGCCTTCCGGTGACGTA

GTCCGTTTCCCAAATATCACTAACTTGTGCCCTTTTGGTGAAGTATTC

AACGCAACCAAATTCCCCAGTGTGTATGCGTGGGAGCGCAAAAAGA

TCAGTAACTGTGTGGCTGACTATAGTGTTCTGTACAATAGCACCTTC

TTCAGCACCTTCAAGTGTTATGGAGTGAGCGCTACAAAACTGAACGA

TCTTTGTTTCTCAAACGTGTACGCCGATTCATTTGTCGTTAAAGGTGA

CGATGTGAGGCAGATCGCTCCAGGCCAGACAGGTGTGATTGCTGAC

TATAATTACAAACTGCCAGACGACTTCATGGGGTGCGTGCTAGCTTG

GAATACAAGAAACATTGACGCCACCTCCACGGGAAATTACAATTAC

AAGTATCGTTACCTTCGCCATGGAAAGTTGAGACCCTTCGAGCGTGA

TATAAGTAACGTGCCCTTTAGTCCAGATGGAAAACCCTGCACACCCC

CTGCTCTCAATTGCTATTGGCCTCTCAATGACTACGGCTTTTACACAA

CTACTGGCATCGGATACCAGCCTTACCGGGTCGTGGTGCTCAGTTTT

GAGTTGCTTAACGCACCCGCCACCGTGTGTGGTCCTAAACTTTCTAC

TGACCTGATTAAAAACCAATGCGTCAACTTCAATTTTAACGGGCTGA

CCGGCACCGGTGTCCTGACCCCTAGCTCTAAGAGATTCCAGCCTTTT

CAGCAGTTCGGGAGGGATGTGAGCGACTTTACCGACTCTGTCAGGG

ATCCAAAGACCAGCGAGATACTGGATATCTCGCCCTGCAGTTTCGGT

GGCGTGTCCGTTATTACACCTGGCACCAACGCCTCCTCAGAGGTGGC

GGTGCTCTATCAAGATGTCAACTGCACTGATGTGTCAACTGCCATCC

ATGCCGATCAGCTGACCCCCGCCTGGCGCATCTACAGTACCGGGAAC

AACGTTTTTCAGACCCAGGCCGGCTGTCTAATCGGCGCAGAGCACGT

TGACACATCCTACGAATGTGACATACCTATCGGGGCAGGCATTTGCG

CTAGCTACCATACCGTGTCACTGTTGGCTTCCACGTCACAAAAGTCA

ATCGTTGCCTACACGATGAGTCTGGGGGCTGACTCATCTATCGCCTA

CAGCAACAATACCATTGCAATTCCCACAAACTTCAGTATCTCCATCA

CAACAGAGGTGATGCCCGTTTCTATGGCTAAAACATCAGTCGATTGC

AATATGTATATATGCGGCGATAGTACTGAGTGCGCCAATCTCTTGTT

ACAGTACGGCTCCTTTTGTACCCAGCTGAACCGAGCACTGTCTGGAA

TCGCCGCAGAACAGGATCGCAATACCCGGGAAGTCTTCGCCCAGGT

GAAGCAGATGTACAAAACGCCCACTCTCAAGTATTTCGGCGGATTCA

ACTTTTCTCAGATTTTGCCTGACCCGCTCAAGCCAACAAAACGATCT

TTTATCGAAGACCTTCTGTTTAACAAGGTCACACTGGCGGATGCTGG

GTTCATGAAACAGTACGGTGAATGCCTGGGGGACATCAATGCCAGA

GATCTGATCTGCGCCCAGAAATTCAATGGCTTAACAGTCCTCCCACC

TCTCTTGACCGACGATATGATCGCTGCGTACACCGCTGCTCTGGTAT

CGGGCACCGCGACTGCTGGCTGGACCTTTGGTGCCGGAGCCGCACTC

CAGATCCCATTCGCCATGCAGATGGCCTACCGCTTCAACGGAATCGG

GGTCACCCAGAACGTGCTGTATGAGAACCAGAAACAGATCGCCAAT

CAGTTCAATAAGGCAATTAGTCAGATTCAGGAGAGTCTTACCACTAC

CAGCACCGCCCTGGGCAAGCTGCAAGATGTTGTGAACCAGAATGCG

CAGGCATTAAACACTCTGGTTAAACAGCTGAGCTCAAATTTTGGTGC

AATCTCTTCAGTTCTGAACGATATCCTGAGTCGGCTGGATCCGCCAG

AGGCTGAAGTGCAAATTGATCGTTTGATCACCGGGAGGCTACAATCT

CTGCAGACGTACGTGACCCAGCAGCTCATCCGGGCAGCCGAAATTC

GCGCATCAGCCAACCTCGCTGCAACTAAGATGTCTGAGTGCGTGCTG

GGCCAGAGTAAGAGGGTGGACTTTTGTGGTAAGGGATACCACCTCA

TGTCCTTTCCGCAAGCGGCTCCCCACGGCGTGGTTTTCTTACACGTTA

CCTATGTGCCATCCCAAGAACGCAATTTCACCACCGCTCCAGCTATC

TGTCATGAGGGCAAAGCATATTTCCCCAGGGAAGGAGTATTTGTGTT

TAATGGCACGTCCTGGTTTATAACCCAACGTAACTTTTTCTCCCCACA

GATTATCACAACCGACAACACATTCGTGTCTGGGAATTGTGACGTCG

TGATCGGGATCATTAACAATACCGTTTACGATCCCTTGCAGCCCGAG

CTTGACTCCTTTAAAGAGGAACTAGACAAATACTTTAAGAATCACAC

CTCACCGGACGTAGATTTGGGAGACATCTCTGGAATTAATGCCTCTG

TGGTGAATATCCAGAAGGAGATCGACCGCCTGAATGAAGTCGCCAA

GAACCTCAACGAGTCCCTGATAGATCTGCAAGAACTGGGCAAATAT

GAACAGTACATCAAATGGCCGTGGTACGTGTGGTTGGGCTTTATCGC

TGGACTTATTGCAATCGTGATGGTGACGATTCTGCTCtgctgctccaatggatc

gttacaatgcagaatttgcattTAA

PDI-SARS-COV-1 H1cCT-DNA(SEQ ID NO：92)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTCCGA

TCTGGATCGGTGCACTACATTTGACGATGTGCAGGCACCTAATTATA

CTCAGCACACCTCTTCCATGCGGGGCGTGTACTACCCCGACGAGATT

TTTAGAAGTGACACACTGTACCTGACCCAAGACCTTTTTCTCCCATTT

TATAGCAATGTCACGGGATTCCACACTATCAATCACACATTCGGAAA

CCCTGTTATCCCCTTTAAAGACGGTATCTACTTTGCTGCTACTGAGAA

ATCGAATGTTGTTCGCGGTTGGGTGTTCGGCTCAACCATGAACAACA

AGAGTCAGTCAGTAATAATTATAAACAACTCAACCAATGTCGTCATC

AGGGCTTGCAACTTCGAGCTCTGCGATAACCCCTTCTTTGCGGTGTC

CAAACCGATGGGCACTCAGACCCATACCATGATTTTTGACAATGCCT

TTAATTGTACTTTCGAATACATCAGCGATGCCTTCTCGCTGGATGTGT

CCGAGAAGAGCGGTAACTTCAAGCATTTGCGGGAGTTCGTTTTCAAA

AACAAAGACGGGTTTTTGTATGTCTACAAAGGCTATCAGCCCATTGA

TGTGGTCAGGGATCTGCCCAGTGGTTTCAACACACTGAAGCCCATCT

TCAAGTTGCCACTCGGCATCAACATCACTAATTTCCGCGCCATCCTA

ACTGCTTTTTCGCCAGCGCAGGATATTTGGGGGACATCCGCCGCAGC

TTACTTCGTGGGATATCTGAAGCCCACCACTTTTATGCTAAAGTACG

ACGAGAATGGCACCATCACCGATGCCGTGGACTGCTCACAGAATCC

TCTCGCAGAGCTCAAGTGTTCAGTGAAGTCATTTGAGATCGACAAAG

GGATCTACCAAACATCTAACTTTCGCGTCGTGCCTTCCGGTGACGTA

GTCCGTTTCCCAAATATCACTAACTTGTGCCCTTTTGGTGAAGTATTC

AACGCAACCAAATTCCCCAGTGTGTATGCGTGGGAGCGCAAAAAGA

TCAGTAACTGTGTGGCTGACTATAGTGTTCTGTACAATAGCACCTTC

TTCAGCACCTTCAAGTGTTATGGAGTGAGCGCTACAAAACTGAACGA

TCTTTGTTTCTCAAACGTGTACGCCGATTCATTTGTCGTTAAAGGTGA

CGATGTGAGGCAGATCGCTCCAGGCCAGACAGGTGTGATTGCTGAC

TATAATTACAAACTGCCAGACGACTTCATGGGGTGCGTGCTAGCTTG

GAATACAAGAAACATTGACGCCACCTCCACGGGAAATTACAATTAC

AAGTATCGTTACCTTCGCCATGGAAAGTTGAGACCCTTCGAGCGTGA

TATAAGTAACGTGCCCTTTAGTCCAGATGGAAAACCCTGCACACCCC

CTGCTCTCAATTGCTATTGGCCTCTCAATGACTACGGCTTTTACACAA

CTACTGGCATCGGATACCAGCCTTACCGGGTCGTGGTGCTCAGTTTT

GAGTTGCTTAACGCACCCGCCACCGTGTGTGGTCCTAAACTTTCTAC

TGACCTGATTAAAAACCAATGCGTCAACTTCAATTTTAACGGGCTGA

CCGGCACCGGTGTCCTGACCCCTAGCTCTAAGAGATTCCAGCCTTTT

CAGCAGTTCGGGAGGGATGTGAGCGACTTTACCGACTCTGTCAGGG

ATCCAAAGACCAGCGAGATACTGGATATCTCGCCCTGCAGTTTCGGT

GGCGTGTCCGTTATTACACCTGGCACCAACGCCTCCTCAGAGGTGGC

GGTGCTCTATCAAGATGTCAACTGCACTGATGTGTCAACTGCCATCC

ATGCCGATCAGCTGACCCCCGCCTGGCGCATCTACAGTACCGGGAAC

AACGTTTTTCAGACCCAGGCCGGCTGTCTAATCGGCGCAGAGCACGT

TGACACATCCTACGAATGTGACATACCTATCGGGGCAGGCATTTGCG

CTAGCTACCATACCGTGTCACTGTTGGCTTCCACGTCACAAAAGTCA

ATCGTTGCCTACACGATGAGTCTGGGGGCTGACTCATCTATCGCCTA

CAGCAACAATACCATTGCAATTCCCACAAACTTCAGTATCTCCATCA

CAACAGAGGTGATGCCCGTTTCTATGGCTAAAACATCAGTCGATTGC

AATATGTATATATGCGGCGATAGTACTGAGTGCGCCAATCTCTTGTT

ACAGTACGGCTCCTTTTGTACCCAGCTGAACCGAGCACTGTCTGGAA

TCGCCGCAGAACAGGATCGCAATACCCGGGAAGTCTTCGCCCAGGT

GAAGCAGATGTACAAAACGCCCACTCTCAAGTATTTCGGCGGATTCA

ACTTTTCTCAGATTTTGCCTGACCCGCTCAAGCCAACAAAACGATCT

TTTATCGAAGACCTTCTGTTTAACAAGGTCACACTGGCGGATGCTGG

GTTCATGAAACAGTACGGTGAATGCCTGGGGGACATCAATGCCAGA

GATCTGATCTGCGCCCAGAAATTCAATGGCTTAACAGTCCTCCCACC

TCTCTTGACCGACGATATGATCGCTGCGTACACCGCTGCTCTGGTAT

CGGGCACCGCGACTGCTGGCTGGACCTTTGGTGCCGGAGCCGCACTC

CAGATCCCATTCGCCATGCAGATGGCCTACCGCTTCAACGGAATCGG

GGTCACCCAGAACGTGCTGTATGAGAACCAGAAACAGATCGCCAAT

CAGTTCAATAAGGCAATTAGTCAGATTCAGGAGAGTCTTACCACTAC

CAGCACCGCCCTGGGCAAGCTGCAAGATGTTGTGAACCAGAATGCG

CAGGCATTAAACACTCTGGTTAAACAGCTGAGCTCAAATTTTGGTGC

AATCTCTTCAGTTCTGAACGATATCCTGAGTCGGCTGGATCCGCCAG

AGGCTGAAGTGCAAATTGATCGTTTGATCACCGGGAGGCTACAATCT

CTGCAGACGTACGTGACCCAGCAGCTCATCCGGGCAGCCGAAATTC

GCGCATCAGCCAACCTCGCTGCAACTAAGATGTCTGAGTGCGTGCTG

GGCCAGAGTAAGAGGGTGGACTTTTGTGGTAAGGGATACCACCTCA

TGTCCTTTCCGCAAGCGGCTCCCCACGGCGTGGTTTTCTTACACGTTA

CCTATGTGCCATCCCAAGAACGCAATTTCACCACCGCTCCAGCTATC

TGTCATGAGGGCAAAGCATATTTCCCCAGGGAAGGAGTATTTGTGTT

TAATGGCACGTCCTGGTTTATAACCCAACGTAACTTTTTCTCCCCACA

GATTATCACAACCGACAACACATTCGTGTCTGGGAATTGTGACGTCG

TGATCGGGATCATTAACAATACCGTTTACGATCCCTTGCAGCCCGAG

CTTGACTCCTTTAAAGAGGAACTAGACAAATACTTTAAGAATCACAC

CTCACCGGACGTAGATTTGGGAGACATCTCTGGAATTAATGCCTCTG

TGGTGAATATCCAGAAGGAGATCGACCGCCTGAATGAAGTCGCCAA

GAACCTCAACGAGTCCCTGATAGATCTGCAAGAACTGGGCAAATAT

GAACAGTACATCAAATGGCCGTGGTACGTGTGGTTGGGCTTTATCGC

TGGACTTATTGCAATCGTGATGGTGACGATTCTGCTCagcttctggatgtgctct

aatgggtctctacagtgtagaatatgtattTAA

PDI-SARS-COV-1 wtTMCT-AA(SEQ ID NO：93)

MAKNVAIFGLLFSLLVLVPSQIFASDLDRCTTFDDVQAPNYTQHTSSMR

GVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYF

AATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFF

AVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVF

KNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAF

SPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAEL

KCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPS

VYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYA

DSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS

TGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLND

YGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNF

NGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFG

GVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNN

VFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLASTSQKSIVAY

TMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGD

STECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPT

LKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLG

DINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGA

GAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT

TTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQS

KRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEG

KAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRL

NEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLC

CMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT

PDI-SARS-COV-1 H5iTMCT-AA(SEQ ID NO：94)

MAKNVAIFGLLFSLLVLVPSQIFASDLDRCTTFDDVQAPNYTQHTSSMR

GVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYF

AATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFF

AVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVF

KNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAF

SPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAEL

KCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPS

VYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYA

DSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS

TGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLND

YGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNF

NGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFG

GVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNN

VFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLASTSQKSIVAY

TMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGD

STECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPT

LKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLG

DINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGA

GAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT

TTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQS

KRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEG

KAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRL

NEVAKNLNESLIDLQELGKYEQYIKWPWYQILSIYSTVASSLALAIMMA

GLSLWMCSNGSLQCRICI

PDI-SARS-COV-1 H5iCT-AA(SEQ ID NO：95)

MAKNVAIFGLLFSLLVLVPSQIFASDLDRCTTFDDVQAPNYTQHTSSMR

GVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYF

AATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFF

AVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVF

KNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAF

SPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAEL

KCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPS

VYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYA

DSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS

TGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLND

YGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNF

NGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFG

GVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNN

VFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLASTSQKSIVAY

TMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGD

STECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPT

LKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLG

DINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGA

GAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT

TTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQS

KRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEG

KAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRL

NEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLS

LWMCSNGSLQCRICI

PDI-SARS-COV-1 H5iCT(V4)-AA(SEQ ID NO：96)

MAKNVAIFGLLFSLLVLVPSQIFASDLDRCTTFDDVQAPNYTQHTSSMR

GVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYF

AATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFF

AVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVF

KNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAF

SPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAEL

KCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPS

VYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYA

DSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS

TGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLND

YGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNF

NGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFG

GVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNN

VFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLASTSQKSIVAY

TMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGD

STECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPT

LKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLG

DINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGA

GAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT

TTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQS

KRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEG

KAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRL

NEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLC

CSNGSLQCRICI

PDI-SARS-COV-1 H1cCT-AA(SEQ ID NO：97)

MAKNVAIFGLLFSLLVLVPSQIFASDLDRCTTFDDVQAPNYTQHTSSMR

GVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYF

AATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFF

AVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVF

KNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAF

SPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAEL

KCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPS

VYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYA

DSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATS

TGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLND

YGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNF

NGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFG

GVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNN

VFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLASTSQKSIVAY

TMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGD

STECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPT

LKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLG

DINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGA

GAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLT

TTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDPPE

AEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQS

KRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEG

KAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNT

VYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRL

NEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLS

FWMCSNGSLQCRICI

IF(AvB+wtCT-MERS).r(SEQ ID NO：98)

ACGACACGACTAAGGCCTTCAGTGAACGTGGACCTTGTGAGGCTCA

AGGTCATACTCCTC

IF(H1cCT-wtTM).r(SEQ ID NO：99)

ACGACACGACTAAGGCCTTCAAATACATATTCTACACTGTAGAGACC

CA

IF(H5ITMCT).r(SEQ ID NO：100)

ACGACACGACTAAGGCCTTCAAATGCAAATTCTGCATTGTAACGATC

C

PDI-MERS-wtTMCT-DNA(SEQ ID NO：101)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTATGT

CGATGTGGGTCCCGATAGTGTTAAGTCCGCCTGCATCGAAGTGGACA

TTCAGCAGACCTTCTTCGATAAGACTTGGCCTCGGCCAATTGATGTG

TCCAAGGCCGACGGCATTATCTACCCCCAAGGTCGGACATATTCCAA

CATAACTATCACCTATCAGGGGCTATTCCCTTATCAGGGCGACCATG

GGGACATGTACGTTTACAGCGCTGGTCACGCTACAGGGACGACCCC

CCAGAAGCTCTTCGTGGCGAACTATAGTCAGGACGTGAAACAGTTTG

CCAACGGTTTTGTAGTGCGCATCGGGGCAGCCGCTAACTCCACTGGT

ACTGTTATTATCAGCCCTTCCACGAGTGCCACAATTCGAAAGATCTA

TCCGGCCTTCATGCTAGGATCCTCTGTGGGCAATTTTAGCGACGGTA

AGATGGGTCGGTTCTTCAACCACACGCTTGTGCTGCTTCCCGATGGG

TGCGGTACTTTGCTGAGGGCCTTTTACTGTATCCTAGAGCCCCGATC

CGGCAACCACTGCCCCGCCGGGAACTCGTATACTTCCTTTGCCACTT

ATCATACTCCAGCCACGGATTGTAGCGATGGGAACTACAATAGGAA

CGCCAGTTTGAATTCCTTTAAAGAGTACTTCAACTTGCGGAATTGTA

CCTTCATGTATACATATAACATTACTGAGGACGAAATTCTCGAATGG

TTCGGAATCACTCAAACAGCCCAGGGAGTGCACCTCTTTAGTTCTCG

CTATGTGGACTTATATGGAGGCAATATGTTTCAATTCGCCACCTTAC

CCGTCTACGATACGATCAAGTATTACTCGATCATACCCCACTCCATT

AGGTCCATTCAGAGCGATCGCAAGGCATGGGCCGCATTCTATGTGTA

TAAGCTCCAGCCCCTGACCTTCCTCTTGGATTTCTCCGTGGACGGCTA

CATCAGAAGGGCTATCGATTGCGGGTTCAACGACCTCAGCCAGCTGC

ATTGTTCTTATGAGAGCTTTGACGTGGAAAGCGGAGTTTACTCAGTC

TCTTCCTTTGAGGCTAAACCTTCAGGTAGCGTCGTAGAGCAAGCAGA

GGGTGTGGAGTGCGATTTCTCACCACTGCTCAGCGGAACCCCACCCC

AGGTCTACAACTTTAAGCGGCTCGTGTTCACAAACTGTAACTATAAC

TTGACTAAGTTGCTGTCACTCTTTTCCGTGAATGATTTTACATGCTCC

CAAATCAGCCCAGCCGCTATTGCGTCTAATTGCTATTCCTCATTGATC

CTGGATTACTTCAGTTACCCCCTCTCTATGAAGAGCGATCTCTCGGTT

AGTAGCGCTGGGCCTATTTCCCAGTTTAACTACAAACAATCCTTTTC

CAATCCAACATGCCTGATCTTAGCTACTGTACCCCACAACCTGACTA

CTATTACGAAGCCACTCAAGTACTCATACATTAATAAGTGCAGCCGA

TTCCTCAGTGATGATCGCACCGAAGTGCCGCAGCTTGTAAACGCGAA

CCAGTACTCCCCATGCGTCTCTATTGTGCCTTCTACAGTGTGGGAAG

ACGGCGATTATTATAGAAAGCAGCTGTCGCCACTGGAAGGTGGCGG

GTGGCTAGTTGCCAGTGGGTCCACAGTTGCCATGACCGAGCAACTTC

AGATGGGGTTTGGCATAACAGTGCAGTATGGTACCGATACGAACAG

CGTGTGTCCAAAATTGGAATTTGCTAACGACACCAAGATCGCCTCCC

AGTTGGGAAATTGTGTTGAATATTCCCTGTACGGAGTGTCAGGCCGG

GGGGTGTTCCAAAATTGCACCGCCGTGGGAGTGAGGCAGCAAAGAT

TCGTGTACGACGCATACCAGAATCTAGTCGGATACTATTCTGACGAT

GGAAACTACTACTGTCTGCGCGCTTGCGTCTCAGTGCCCGTGAGTGT

CATATATGATAAGGAGACCAAGACTCACGCTACTCTCTTTGGTTCTG

TCGCGTGCGAACACATTTCCTCTACAATGTCCCAGTATAGTCGCTCC

ACTCGGTCTATGTTAAAGCGCAGAGACAGTACCTACGGCCCTCTACA

GACACCTGTGGGGTGCGTTCTCGGCCTTGTCAATTCTAGCCTGTTTGT

GGAGGATTGTAAGCTGCCCCTTGGTCAAAGCTTATGCGCACTGCCCG

ATACGCCCAGCACACTTACACCAGCTTCAGTGGGGTCCGTCCCCGGG

GAAATGAGATTGGCCTCGATCGCTTTCAACCACCCCATACAGGTGGA

TCAGCTCAACTCGTCATACTTCAAGCTAAGCATCCCTACTAATTTCTC

CTTTGGTGTGACTCAGGAGTACATTCAGACCACAATTCAAAAGGTGA

CCGTTGACTGCAAGCAGTATGTGTGCAACGGGTTCCAGAAATGTGA

ACAGCTGCTCCGGGAGTATGGCCAGTTCTGTTCTAAAATCAACCAGG

CCCTCCACGGAGCAAACCTTAGGCAGGACGATTCTGTCAGAAACCTC

TTTGCCAGCGTCAAGAGTTCTCAGAGTTCCCCTATTATACCTGGCTTC

GGCGGGGATTTCAACCTGACACTACTTGAACCTGTAAGCATATCAAC

CGGAAGTCGCAGTGCCCGTTCCGCCATCGAGGATCTGCTCTTCGACA

AAGTAACTATTGCAGATCCCGGATACATGCAGGGGTATGACGACTG

CATGCAGCAGGGTCCAGCCTCTGCAAGGGATCTGATATGCGCACAG

TATGTCGCTGGGTACAAAGTGTTGCCTCCTCTCATGGACGTGAACAT

GGAAGCGGCCTATACCTCCTCACTTCTAGGCTCCATAGCGGGCGTGG

GATGGACCGCAGGGCTTTCAAGCTTCGCCGCAATTCCCTTTGCTCAA

TCTATCTTCTACAGGCTTAATGGCGTTGGAATCACCCAGCAGGTGTT

AAGCGAAAACCAGAAATTGATTGCCAATAAGTTTAACCAAGCTTTG

GGGGCCATGCAGACAGGCTTTACAACCACAAACGAGGCTTTCCATA

AAGTACAGGATGCGGTAAACAATAACGCACAAGCCCTGTCAAAGCT

GGCTTCAGAGCTCTCAAATACATTTGGCGCTATATCCGCGTCTATCG

GCGATATCATACAACGGTTGGACCCACCCGAACAGGACGCACAGAT

TGATCGTTTGATCAACGGGAGGCTTACCACCTTAAACGCTTTTGTGG

CCCAGCAACTGGTGCGGTCTGAGAGCGCCGCCTTGAGCGCTCAGCTG

GCAAAGGATAAAGTGAATGAATGCGTGAAAGCTCAATCAAAGAGAA

GTGGGTTTTGTGGGCAGGGTACTCATATTGTTTCCTTTGTGGTGAAC

GCCCCAAATGGACTCTACTTTATGCATGTTGGATACTACCCGAGCAA

CCACATCGAGGTCGTTTCCGCCTATGGGCTTTGTGACGCAGCAAACC

CTACTAACTGTATCGCGCCAGTTAATGGCTACTTTATTAAAACAAAT

AACACACGCATTGTGGATGAATGGAGTTACACAGGGTCCAGCTTCTA

CGCTCCAGAGCCTATCACCTCTCTGAACACAAAGTATGTGGCACCTC

AGGTCACATATCAGAACATCTCGACAAACCTGCCCCCCCCACTCTTG

GGCAACTCCACAGGGATCGACTTCCAGGACGAGCTTGACGAATTCTT

CAAGAACGTGTCCACCAGTATCCCTAATTTTGGTTCGCTGACCCAAA

TTAACACAACCCTGCTCGATCTGACATATGAAATGCTTTCACTACAG

CAGGTGGTCAAAGCGTTGAACGAGTCGTATATCGACCTGAAAGAGT

TAGGGAATTACACATACTATAACAAATGGCCCTGGTATATTTGGTTA

GGATTCATTGCCGGGCTGGTGGCCCTTGCCTTGTGCGTATTTTTCATC

TTGTGCTGTACCGGTTGCGGTACGAATTGCATGGGAAAACTGAAATG

TAATCGGTGCTGCGATCGCTATGAGGAGTATGACCTTGAGCCTCACA

AGGTCCACGTTCACTGA

PDI-MERS-H5iTMCT-DNA(SEQ ID NO：102)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTATGT

CGATGTGGGTCCCGATAGTGTTAAGTCCGCCTGCATCGAAGTGGACA

TTCAGCAGACCTTCTTCGATAAGACTTGGCCTCGGCCAATTGATGTG

TCCAAGGCCGACGGCATTATCTACCCCCAAGGTCGGACATATTCCAA

CATAACTATCACCTATCAGGGGCTATTCCCTTATCAGGGCGACCATG

GGGACATGTACGTTTACAGCGCTGGTCACGCTACAGGGACGACCCC

CCAGAAGCTCTTCGTGGCGAACTATAGTCAGGACGTGAAACAGTTTG

CCAACGGTTTTGTAGTGCGCATCGGGGCAGCCGCTAACTCCACTGGT

ACTGTTATTATCAGCCCTTCCACGAGTGCCACAATTCGAAAGATCTA

TCCGGCCTTCATGCTAGGATCCTCTGTGGGCAATTTTAGCGACGGTA

AGATGGGTCGGTTCTTCAACCACACGCTTGTGCTGCTTCCCGATGGG

TGCGGTACTTTGCTGAGGGCCTTTTACTGTATCCTAGAGCCCCGATC

CGGCAACCACTGCCCCGCCGGGAACTCGTATACTTCCTTTGCCACTT

ATCATACTCCAGCCACGGATTGTAGCGATGGGAACTACAATAGGAA

CGCCAGTTTGAATTCCTTTAAAGAGTACTTCAACTTGCGGAATTGTA

CCTTCATGTATACATATAACATTACTGAGGACGAAATTCTCGAATGG

TTCGGAATCACTCAAACAGCCCAGGGAGTGCACCTCTTTAGTTCTCG

CTATGTGGACTTATATGGAGGCAATATGTTTCAATTCGCCACCTTAC

CCGTCTACGATACGATCAAGTATTACTCGATCATACCCCACTCCATT

AGGTCCATTCAGAGCGATCGCAAGGCATGGGCCGCATTCTATGTGTA

TAAGCTCCAGCCCCTGACCTTCCTCTTGGATTTCTCCGTGGACGGCTA

CATCAGAAGGGCTATCGATTGCGGGTTCAACGACCTCAGCCAGCTGC

ATTGTTCTTATGAGAGCTTTGACGTGGAAAGCGGAGTTTACTCAGTC

TCTTCCTTTGAGGCTAAACCTTCAGGTAGCGTCGTAGAGCAAGCAGA

GGGTGTGGAGTGCGATTTCTCACCACTGCTCAGCGGAACCCCACCCC

AGGTCTACAACTTTAAGCGGCTCGTGTTCACAAACTGTAACTATAAC

TTGACTAAGTTGCTGTCACTCTTTTCCGTGAATGATTTTACATGCTCC

CAAATCAGCCCAGCCGCTATTGCGTCTAATTGCTATTCCTCATTGATC

CTGGATTACTTCAGTTACCCCCTCTCTATGAAGAGCGATCTCTCGGTT

AGTAGCGCTGGGCCTATTTCCCAGTTTAACTACAAACAATCCTTTTC

CAATCCAACATGCCTGATCTTAGCTACTGTACCCCACAACCTGACTA

CTATTACGAAGCCACTCAAGTACTCATACATTAATAAGTGCAGCCGA

TTCCTCAGTGATGATCGCACCGAAGTGCCGCAGCTTGTAAACGCGAA

CCAGTACTCCCCATGCGTCTCTATTGTGCCTTCTACAGTGTGGGAAG

ACGGCGATTATTATAGAAAGCAGCTGTCGCCACTGGAAGGTGGCGG

GTGGCTAGTTGCCAGTGGGTCCACAGTTGCCATGACCGAGCAACTTC

AGATGGGGTTTGGCATAACAGTGCAGTATGGTACCGATACGAACAG

CGTGTGTCCAAAATTGGAATTTGCTAACGACACCAAGATCGCCTCCC

AGTTGGGAAATTGTGTTGAATATTCCCTGTACGGAGTGTCAGGCCGG

GGGGTGTTCCAAAATTGCACCGCCGTGGGAGTGAGGCAGCAAAGAT

TCGTGTACGACGCATACCAGAATCTAGTCGGATACTATTCTGACGAT

GGAAACTACTACTGTCTGCGCGCTTGCGTCTCAGTGCCCGTGAGTGT

CATATATGATAAGGAGACCAAGACTCACGCTACTCTCTTTGGTTCTG

TCGCGTGCGAACACATTTCCTCTACAATGTCCCAGTATAGTCGCTCC

ACTCGGTCTATGTTAAAGCGCAGAGACAGTACCTACGGCCCTCTACA

GACACCTGTGGGGTGCGTTCTCGGCCTTGTCAATTCTAGCCTGTTTGT

GGAGGATTGTAAGCTGCCCCTTGGTCAAAGCTTATGCGCACTGCCCG

ATACGCCCAGCACACTTACACCAGCTTCAGTGGGGTCCGTCCCCGGG

GAAATGAGATTGGCCTCGATCGCTTTCAACCACCCCATACAGGTGGA

TCAGCTCAACTCGTCATACTTCAAGCTAAGCATCCCTACTAATTTCTC

CTTTGGTGTGACTCAGGAGTACATTCAGACCACAATTCAAAAGGTGA

CCGTTGACTGCAAGCAGTATGTGTGCAACGGGTTCCAGAAATGTGA

ACAGCTGCTCCGGGAGTATGGCCAGTTCTGTTCTAAAATCAACCAGG

CCCTCCACGGAGCAAACCTTAGGCAGGACGATTCTGTCAGAAACCTC

TTTGCCAGCGTCAAGAGTTCTCAGAGTTCCCCTATTATACCTGGCTTC

GGCGGGGATTTCAACCTGACACTACTTGAACCTGTAAGCATATCAAC

CGGAAGTCGCAGTGCCCGTTCCGCCATCGAGGATCTGCTCTTCGACA

AAGTAACTATTGCAGATCCCGGATACATGCAGGGGTATGACGACTG

CATGCAGCAGGGTCCAGCCTCTGCAAGGGATCTGATATGCGCACAG

TATGTCGCTGGGTACAAAGTGTTGCCTCCTCTCATGGACGTGAACAT

GGAAGCGGCCTATACCTCCTCACTTCTAGGCTCCATAGCGGGCGTGG

GATGGACCGCAGGGCTTTCAAGCTTCGCCGCAATTCCCTTTGCTCAA

TCTATCTTCTACAGGCTTAATGGCGTTGGAATCACCCAGCAGGTGTT

AAGCGAAAACCAGAAATTGATTGCCAATAAGTTTAACCAAGCTTTG

GGGGCCATGCAGACAGGCTTTACAACCACAAACGAGGCTTTCCATA

AAGTACAGGATGCGGTAAACAATAACGCACAAGCCCTGTCAAAGCT

GGCTTCAGAGCTCTCAAATACATTTGGCGCTATATCCGCGTCTATCG

GCGATATCATACAACGGTTGGACCCACCCGAACAGGACGCACAGAT

TGATCGTTTGATCAACGGGAGGCTTACCACCTTAAACGCTTTTGTGG

CCCAGCAACTGGTGCGGTCTGAGAGCGCCGCCTTGAGCGCTCAGCTG

GCAAAGGATAAAGTGAATGAATGCGTGAAAGCTCAATCAAAGAGAA

GTGGGTTTTGTGGGCAGGGTACTCATATTGTTTCCTTTGTGGTGAAC

GCCCCAAATGGACTCTACTTTATGCATGTTGGATACTACCCGAGCAA

CCACATCGAGGTCGTTTCCGCCTATGGGCTTTGTGACGCAGCAAACC

CTACTAACTGTATCGCGCCAGTTAATGGCTACTTTATTAAAACAAAT

AACACACGCATTGTGGATGAATGGAGTTACACAGGGTCCAGCTTCTA

CGCTCCAGAGCCTATCACCTCTCTGAACACAAAGTATGTGGCACCTC

AGGTCACATATCAGAACATCTCGACAAACCTGCCCCCCCCACTCTTG

GGCAACTCCACAGGGATCGACTTCCAGGACGAGCTTGACGAATTCTT

CAAGAACGTGTCCACCAGTATCCCTAATTTTGGTTCGCTGACCCAAA

TTAACACAACCCTGCTCGATCTGACATATGAAATGCTTTCACTACAG

CAGGTGGTCAAAGCGTTGAACGAGTCGTATATCGACCTGAAAGAGT

TAGGGAATTACACATACTATAACAAATGGCCCTGGTATcaaatactgtcaatt

tattcaacagtggcgagttccctagcactggcaatcatgatggctggtctatctttatggatgtgctccaatggatc

gttacaatgcagaatttgcattTGA

PDI-MERS-H5iCT-DNA(SEQ ID NO：103)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTATGT

CGATGTGGGTCCCGATAGTGTTAAGTCCGCCTGCATCGAAGTGGACA

TTCAGCAGACCTTCTTCGATAAGACTTGGCCTCGGCCAATTGATGTG

TCCAAGGCCGACGGCATTATCTACCCCCAAGGTCGGACATATTCCAA

CATAACTATCACCTATCAGGGGCTATTCCCTTATCAGGGCGACCATG

GGGACATGTACGTTTACAGCGCTGGTCACGCTACAGGGACGACCCC

CCAGAAGCTCTTCGTGGCGAACTATAGTCAGGACGTGAAACAGTTTG

CCAACGGTTTTGTAGTGCGCATCGGGGCAGCCGCTAACTCCACTGGT

ACTGTTATTATCAGCCCTTCCACGAGTGCCACAATTCGAAAGATCTA

TCCGGCCTTCATGCTAGGATCCTCTGTGGGCAATTTTAGCGACGGTA

AGATGGGTCGGTTCTTCAACCACACGCTTGTGCTGCTTCCCGATGGG

TGCGGTACTTTGCTGAGGGCCTTTTACTGTATCCTAGAGCCCCGATC

CGGCAACCACTGCCCCGCCGGGAACTCGTATACTTCCTTTGCCACTT

ATCATACTCCAGCCACGGATTGTAGCGATGGGAACTACAATAGGAA

CGCCAGTTTGAATTCCTTTAAAGAGTACTTCAACTTGCGGAATTGTA

CCTTCATGTATACATATAACATTACTGAGGACGAAATTCTCGAATGG

TTCGGAATCACTCAAACAGCCCAGGGAGTGCACCTCTTTAGTTCTCG

CTATGTGGACTTATATGGAGGCAATATGTTTCAATTCGCCACCTTAC

CCGTCTACGATACGATCAAGTATTACTCGATCATACCCCACTCCATT

AGGTCCATTCAGAGCGATCGCAAGGCATGGGCCGCATTCTATGTGTA

TAAGCTCCAGCCCCTGACCTTCCTCTTGGATTTCTCCGTGGACGGCTA

CATCAGAAGGGCTATCGATTGCGGGTTCAACGACCTCAGCCAGCTGC

ATTGTTCTTATGAGAGCTTTGACGTGGAAAGCGGAGTTTACTCAGTC

TCTTCCTTTGAGGCTAAACCTTCAGGTAGCGTCGTAGAGCAAGCAGA

GGGTGTGGAGTGCGATTTCTCACCACTGCTCAGCGGAACCCCACCCC

AGGTCTACAACTTTAAGCGGCTCGTGTTCACAAACTGTAACTATAAC

TTGACTAAGTTGCTGTCACTCTTTTCCGTGAATGATTTTACATGCTCC

CAAATCAGCCCAGCCGCTATTGCGTCTAATTGCTATTCCTCATTGATC

CTGGATTACTTCAGTTACCCCCTCTCTATGAAGAGCGATCTCTCGGTT

AGTAGCGCTGGGCCTATTTCCCAGTTTAACTACAAACAATCCTTTTC

CAATCCAACATGCCTGATCTTAGCTACTGTACCCCACAACCTGACTA

CTATTACGAAGCCACTCAAGTACTCATACATTAATAAGTGCAGCCGA

TTCCTCAGTGATGATCGCACCGAAGTGCCGCAGCTTGTAAACGCGAA

CCAGTACTCCCCATGCGTCTCTATTGTGCCTTCTACAGTGTGGGAAG

ACGGCGATTATTATAGAAAGCAGCTGTCGCCACTGGAAGGTGGCGG

GTGGCTAGTTGCCAGTGGGTCCACAGTTGCCATGACCGAGCAACTTC

AGATGGGGTTTGGCATAACAGTGCAGTATGGTACCGATACGAACAG

CGTGTGTCCAAAATTGGAATTTGCTAACGACACCAAGATCGCCTCCC

AGTTGGGAAATTGTGTTGAATATTCCCTGTACGGAGTGTCAGGCCGG

GGGGTGTTCCAAAATTGCACCGCCGTGGGAGTGAGGCAGCAAAGAT

TCGTGTACGACGCATACCAGAATCTAGTCGGATACTATTCTGACGAT

GGAAACTACTACTGTCTGCGCGCTTGCGTCTCAGTGCCCGTGAGTGT

CATATATGATAAGGAGACCAAGACTCACGCTACTCTCTTTGGTTCTG

TCGCGTGCGAACACATTTCCTCTACAATGTCCCAGTATAGTCGCTCC

ACTCGGTCTATGTTAAAGCGCAGAGACAGTACCTACGGCCCTCTACA

GACACCTGTGGGGTGCGTTCTCGGCCTTGTCAATTCTAGCCTGTTTGT

GGAGGATTGTAAGCTGCCCCTTGGTCAAAGCTTATGCGCACTGCCCG

ATACGCCCAGCACACTTACACCAGCTTCAGTGGGGTCCGTCCCCGGG

GAAATGAGATTGGCCTCGATCGCTTTCAACCACCCCATACAGGTGGA

TCAGCTCAACTCGTCATACTTCAAGCTAAGCATCCCTACTAATTTCTC

CTTTGGTGTGACTCAGGAGTACATTCAGACCACAATTCAAAAGGTGA

CCGTTGACTGCAAGCAGTATGTGTGCAACGGGTTCCAGAAATGTGA

ACAGCTGCTCCGGGAGTATGGCCAGTTCTGTTCTAAAATCAACCAGG

CCCTCCACGGAGCAAACCTTAGGCAGGACGATTCTGTCAGAAACCTC

TTTGCCAGCGTCAAGAGTTCTCAGAGTTCCCCTATTATACCTGGCTTC

GGCGGGGATTTCAACCTGACACTACTTGAACCTGTAAGCATATCAAC

CGGAAGTCGCAGTGCCCGTTCCGCCATCGAGGATCTGCTCTTCGACA

AAGTAACTATTGCAGATCCCGGATACATGCAGGGGTATGACGACTG

CATGCAGCAGGGTCCAGCCTCTGCAAGGGATCTGATATGCGCACAG

TATGTCGCTGGGTACAAAGTGTTGCCTCCTCTCATGGACGTGAACAT

GGAAGCGGCCTATACCTCCTCACTTCTAGGCTCCATAGCGGGCGTGG

GATGGACCGCAGGGCTTTCAAGCTTCGCCGCAATTCCCTTTGCTCAA

TCTATCTTCTACAGGCTTAATGGCGTTGGAATCACCCAGCAGGTGTT

AAGCGAAAACCAGAAATTGATTGCCAATAAGTTTAACCAAGCTTTG

GGGGCCATGCAGACAGGCTTTACAACCACAAACGAGGCTTTCCATA

AAGTACAGGATGCGGTAAACAATAACGCACAAGCCCTGTCAAAGCT

GGCTTCAGAGCTCTCAAATACATTTGGCGCTATATCCGCGTCTATCG

GCGATATCATACAACGGTTGGACCCACCCGAACAGGACGCACAGAT

TGATCGTTTGATCAACGGGAGGCTTACCACCTTAAACGCTTTTGTGG

CCCAGCAACTGGTGCGGTCTGAGAGCGCCGCCTTGAGCGCTCAGCTG

GCAAAGGATAAAGTGAATGAATGCGTGAAAGCTCAATCAAAGAGAA

GTGGGTTTTGTGGGCAGGGTACTCATATTGTTTCCTTTGTGGTGAAC

GCCCCAAATGGACTCTACTTTATGCATGTTGGATACTACCCGAGCAA

CCACATCGAGGTCGTTTCCGCCTATGGGCTTTGTGACGCAGCAAACC

CTACTAACTGTATCGCGCCAGTTAATGGCTACTTTATTAAAACAAAT

AACACACGCATTGTGGATGAATGGAGTTACACAGGGTCCAGCTTCTA

CGCTCCAGAGCCTATCACCTCTCTGAACACAAAGTATGTGGCACCTC

AGGTCACATATCAGAACATCTCGACAAACCTGCCCCCCCCACTCTTG

GGCAACTCCACAGGGATCGACTTCCAGGACGAGCTTGACGAATTCTT

CAAGAACGTGTCCACCAGTATCCCTAATTTTGGTTCGCTGACCCAAA

TTAACACAACCCTGCTCGATCTGACATATGAAATGCTTTCACTACAG

CAGGTGGTCAAAGCGTTGAACGAGTCGTATATCGACCTGAAAGAGT

TAGGGAATTACACATACTATAACAAATGGCCCTGGTATATTTGGTTA

GGATTCATTGCCGGGCTGGTGGCCCTTGCCTTGTGCGTATTTTTCATC

TTGtctttatggatgtgctccaatggatcgttacaatgcagaatttgcattTGA

PDI-MERS-H5iCT(V4)-DNA(SEQ ID NO：104)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTATGT

CGATGTGGGTCCCGATAGTGTTAAGTCCGCCTGCATCGAAGTGGACA

TTCAGCAGACCTTCTTCGATAAGACTTGGCCTCGGCCAATTGATGTG

TCCAAGGCCGACGGCATTATCTACCCCCAAGGTCGGACATATTCCAA

CATAACTATCACCTATCAGGGGCTATTCCCTTATCAGGGCGACCATG

GGGACATGTACGTTTACAGCGCTGGTCACGCTACAGGGACGACCCC

CCAGAAGCTCTTCGTGGCGAACTATAGTCAGGACGTGAAACAGTTTG

CCAACGGTTTTGTAGTGCGCATCGGGGCAGCCGCTAACTCCACTGGT

ACTGTTATTATCAGCCCTTCCACGAGTGCCACAATTCGAAAGATCTA

TCCGGCCTTCATGCTAGGATCCTCTGTGGGCAATTTTAGCGACGGTA

AGATGGGTCGGTTCTTCAACCACACGCTTGTGCTGCTTCCCGATGGG

TGCGGTACTTTGCTGAGGGCCTTTTACTGTATCCTAGAGCCCCGATC

CGGCAACCACTGCCCCGCCGGGAACTCGTATACTTCCTTTGCCACTT

ATCATACTCCAGCCACGGATTGTAGCGATGGGAACTACAATAGGAA

CGCCAGTTTGAATTCCTTTAAAGAGTACTTCAACTTGCGGAATTGTA

CCTTCATGTATACATATAACATTACTGAGGACGAAATTCTCGAATGG

TTCGGAATCACTCAAACAGCCCAGGGAGTGCACCTCTTTAGTTCTCG

CTATGTGGACTTATATGGAGGCAATATGTTTCAATTCGCCACCTTAC

CCGTCTACGATACGATCAAGTATTACTCGATCATACCCCACTCCATT

AGGTCCATTCAGAGCGATCGCAAGGCATGGGCCGCATTCTATGTGTA

TAAGCTCCAGCCCCTGACCTTCCTCTTGGATTTCTCCGTGGACGGCTA

CATCAGAAGGGCTATCGATTGCGGGTTCAACGACCTCAGCCAGCTGC

ATTGTTCTTATGAGAGCTTTGACGTGGAAAGCGGAGTTTACTCAGTC

TCTTCCTTTGAGGCTAAACCTTCAGGTAGCGTCGTAGAGCAAGCAGA

GGGTGTGGAGTGCGATTTCTCACCACTGCTCAGCGGAACCCCACCCC

AGGTCTACAACTTTAAGCGGCTCGTGTTCACAAACTGTAACTATAAC

TTGACTAAGTTGCTGTCACTCTTTTCCGTGAATGATTTTACATGCTCC

CAAATCAGCCCAGCCGCTATTGCGTCTAATTGCTATTCCTCATTGATC

CTGGATTACTTCAGTTACCCCCTCTCTATGAAGAGCGATCTCTCGGTT

AGTAGCGCTGGGCCTATTTCCCAGTTTAACTACAAACAATCCTTTTC

CAATCCAACATGCCTGATCTTAGCTACTGTACCCCACAACCTGACTA

CTATTACGAAGCCACTCAAGTACTCATACATTAATAAGTGCAGCCGA

TTCCTCAGTGATGATCGCACCGAAGTGCCGCAGCTTGTAAACGCGAA

CCAGTACTCCCCATGCGTCTCTATTGTGCCTTCTACAGTGTGGGAAG

ACGGCGATTATTATAGAAAGCAGCTGTCGCCACTGGAAGGTGGCGG

GTGGCTAGTTGCCAGTGGGTCCACAGTTGCCATGACCGAGCAACTTC

AGATGGGGTTTGGCATAACAGTGCAGTATGGTACCGATACGAACAG

CGTGTGTCCAAAATTGGAATTTGCTAACGACACCAAGATCGCCTCCC

AGTTGGGAAATTGTGTTGAATATTCCCTGTACGGAGTGTCAGGCCGG

GGGGTGTTCCAAAATTGCACCGCCGTGGGAGTGAGGCAGCAAAGAT

TCGTGTACGACGCATACCAGAATCTAGTCGGATACTATTCTGACGAT

GGAAACTACTACTGTCTGCGCGCTTGCGTCTCAGTGCCCGTGAGTGT

CATATATGATAAGGAGACCAAGACTCACGCTACTCTCTTTGGTTCTG

TCGCGTGCGAACACATTTCCTCTACAATGTCCCAGTATAGTCGCTCC

ACTCGGTCTATGTTAAAGCGCAGAGACAGTACCTACGGCCCTCTACA

GACACCTGTGGGGTGCGTTCTCGGCCTTGTCAATTCTAGCCTGTTTGT

GGAGGATTGTAAGCTGCCCCTTGGTCAAAGCTTATGCGCACTGCCCG

ATACGCCCAGCACACTTACACCAGCTTCAGTGGGGTCCGTCCCCGGG

GAAATGAGATTGGCCTCGATCGCTTTCAACCACCCCATACAGGTGGA

TCAGCTCAACTCGTCATACTTCAAGCTAAGCATCCCTACTAATTTCTC

CTTTGGTGTGACTCAGGAGTACATTCAGACCACAATTCAAAAGGTGA

CCGTTGACTGCAAGCAGTATGTGTGCAACGGGTTCCAGAAATGTGA

ACAGCTGCTCCGGGAGTATGGCCAGTTCTGTTCTAAAATCAACCAGG

CCCTCCACGGAGCAAACCTTAGGCAGGACGATTCTGTCAGAAACCTC

TTTGCCAGCGTCAAGAGTTCTCAGAGTTCCCCTATTATACCTGGCTTC

GGCGGGGATTTCAACCTGACACTACTTGAACCTGTAAGCATATCAAC

CGGAAGTCGCAGTGCCCGTTCCGCCATCGAGGATCTGCTCTTCGACA

AAGTAACTATTGCAGATCCCGGATACATGCAGGGGTATGACGACTG

CATGCAGCAGGGTCCAGCCTCTGCAAGGGATCTGATATGCGCACAG

TATGTCGCTGGGTACAAAGTGTTGCCTCCTCTCATGGACGTGAACAT

GGAAGCGGCCTATACCTCCTCACTTCTAGGCTCCATAGCGGGCGTGG

GATGGACCGCAGGGCTTTCAAGCTTCGCCGCAATTCCCTTTGCTCAA

TCTATCTTCTACAGGCTTAATGGCGTTGGAATCACCCAGCAGGTGTT

AAGCGAAAACCAGAAATTGATTGCCAATAAGTTTAACCAAGCTTTG

GGGGCCATGCAGACAGGCTTTACAACCACAAACGAGGCTTTCCATA

AAGTACAGGATGCGGTAAACAATAACGCACAAGCCCTGTCAAAGCT

GGCTTCAGAGCTCTCAAATACATTTGGCGCTATATCCGCGTCTATCG

GCGATATCATACAACGGTTGGACCCACCCGAACAGGACGCACAGAT

TGATCGTTTGATCAACGGGAGGCTTACCACCTTAAACGCTTTTGTGG

CCCAGCAACTGGTGCGGTCTGAGAGCGCCGCCTTGAGCGCTCAGCTG

GCAAAGGATAAAGTGAATGAATGCGTGAAAGCTCAATCAAAGAGAA

GTGGGTTTTGTGGGCAGGGTACTCATATTGTTTCCTTTGTGGTGAAC

GCCCCAAATGGACTCTACTTTATGCATGTTGGATACTACCCGAGCAA

CCACATCGAGGTCGTTTCCGCCTATGGGCTTTGTGACGCAGCAAACC

CTACTAACTGTATCGCGCCAGTTAATGGCTACTTTATTAAAACAAAT

AACACACGCATTGTGGATGAATGGAGTTACACAGGGTCCAGCTTCTA

CGCTCCAGAGCCTATCACCTCTCTGAACACAAAGTATGTGGCACCTC

AGGTCACATATCAGAACATCTCGACAAACCTGCCCCCCCCACTCTTG

GGCAACTCCACAGGGATCGACTTCCAGGACGAGCTTGACGAATTCTT

CAAGAACGTGTCCACCAGTATCCCTAATTTTGGTTCGCTGACCCAAA

TTAACACAACCCTGCTCGATCTGACATATGAAATGCTTTCACTACAG

CAGGTGGTCAAAGCGTTGAACGAGTCGTATATCGACCTGAAAGAGT

TAGGGAATTACACATACTATAACAAATGGCCCTGGTATATTTGGTTA

GGATTCATTGCCGGGCTGGTGGCCCTTGCCTTGTGCGTATTTTTCATC

TTGtgctgctccaatggatcgttacaatgcagaatttgcattTGA

PDI-MERS-H1cCT-DNA(SEQ ID NO：105)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgTATGT

CGATGTGGGTCCCGATAGTGTTAAGTCCGCCTGCATCGAAGTGGACA

TTCAGCAGACCTTCTTCGATAAGACTTGGCCTCGGCCAATTGATGTG

TCCAAGGCCGACGGCATTATCTACCCCCAAGGTCGGACATATTCCAA

CATAACTATCACCTATCAGGGGCTATTCCCTTATCAGGGCGACCATG

GGGACATGTACGTTTACAGCGCTGGTCACGCTACAGGGACGACCCC

CCAGAAGCTCTTCGTGGCGAACTATAGTCAGGACGTGAAACAGTTTG

CCAACGGTTTTGTAGTGCGCATCGGGGCAGCCGCTAACTCCACTGGT

ACTGTTATTATCAGCCCTTCCACGAGTGCCACAATTCGAAAGATCTA

TCCGGCCTTCATGCTAGGATCCTCTGTGGGCAATTTTAGCGACGGTA

AGATGGGTCGGTTCTTCAACCACACGCTTGTGCTGCTTCCCGATGGG

TGCGGTACTTTGCTGAGGGCCTTTTACTGTATCCTAGAGCCCCGATC

CGGCAACCACTGCCCCGCCGGGAACTCGTATACTTCCTTTGCCACTT

ATCATACTCCAGCCACGGATTGTAGCGATGGGAACTACAATAGGAA

CGCCAGTTTGAATTCCTTTAAAGAGTACTTCAACTTGCGGAATTGTA

CCTTCATGTATACATATAACATTACTGAGGACGAAATTCTCGAATGG

TTCGGAATCACTCAAACAGCCCAGGGAGTGCACCTCTTTAGTTCTCG

CTATGTGGACTTATATGGAGGCAATATGTTTCAATTCGCCACCTTAC

CCGTCTACGATACGATCAAGTATTACTCGATCATACCCCACTCCATT

AGGTCCATTCAGAGCGATCGCAAGGCATGGGCCGCATTCTATGTGTA

TAAGCTCCAGCCCCTGACCTTCCTCTTGGATTTCTCCGTGGACGGCTA

CATCAGAAGGGCTATCGATTGCGGGTTCAACGACCTCAGCCAGCTGC

ATTGTTCTTATGAGAGCTTTGACGTGGAAAGCGGAGTTTACTCAGTC

TCTTCCTTTGAGGCTAAACCTTCAGGTAGCGTCGTAGAGCAAGCAGA

GGGTGTGGAGTGCGATTTCTCACCACTGCTCAGCGGAACCCCACCCC

AGGTCTACAACTTTAAGCGGCTCGTGTTCACAAACTGTAACTATAAC

TTGACTAAGTTGCTGTCACTCTTTTCCGTGAATGATTTTACATGCTCC

CAAATCAGCCCAGCCGCTATTGCGTCTAATTGCTATTCCTCATTGATC

CTGGATTACTTCAGTTACCCCCTCTCTATGAAGAGCGATCTCTCGGTT

AGTAGCGCTGGGCCTATTTCCCAGTTTAACTACAAACAATCCTTTTC

CAATCCAACATGCCTGATCTTAGCTACTGTACCCCACAACCTGACTA

CTATTACGAAGCCACTCAAGTACTCATACATTAATAAGTGCAGCCGA

TTCCTCAGTGATGATCGCACCGAAGTGCCGCAGCTTGTAAACGCGAA

CCAGTACTCCCCATGCGTCTCTATTGTGCCTTCTACAGTGTGGGAAG

ACGGCGATTATTATAGAAAGCAGCTGTCGCCACTGGAAGGTGGCGG

GTGGCTAGTTGCCAGTGGGTCCACAGTTGCCATGACCGAGCAACTTC

AGATGGGGTTTGGCATAACAGTGCAGTATGGTACCGATACGAACAG

CGTGTGTCCAAAATTGGAATTTGCTAACGACACCAAGATCGCCTCCC

AGTTGGGAAATTGTGTTGAATATTCCCTGTACGGAGTGTCAGGCCGG

GGGGTGTTCCAAAATTGCACCGCCGTGGGAGTGAGGCAGCAAAGAT

TCGTGTACGACGCATACCAGAATCTAGTCGGATACTATTCTGACGAT

GGAAACTACTACTGTCTGCGCGCTTGCGTCTCAGTGCCCGTGAGTGT

CATATATGATAAGGAGACCAAGACTCACGCTACTCTCTTTGGTTCTG

TCGCGTGCGAACACATTTCCTCTACAATGTCCCAGTATAGTCGCTCC

ACTCGGTCTATGTTAAAGCGCAGAGACAGTACCTACGGCCCTCTACA

GACACCTGTGGGGTGCGTTCTCGGCCTTGTCAATTCTAGCCTGTTTGT

GGAGGATTGTAAGCTGCCCCTTGGTCAAAGCTTATGCGCACTGCCCG

ATACGCCCAGCACACTTACACCAGCTTCAGTGGGGTCCGTCCCCGGG

GAAATGAGATTGGCCTCGATCGCTTTCAACCACCCCATACAGGTGGA

TCAGCTCAACTCGTCATACTTCAAGCTAAGCATCCCTACTAATTTCTC

CTTTGGTGTGACTCAGGAGTACATTCAGACCACAATTCAAAAGGTGA

CCGTTGACTGCAAGCAGTATGTGTGCAACGGGTTCCAGAAATGTGA

ACAGCTGCTCCGGGAGTATGGCCAGTTCTGTTCTAAAATCAACCAGG

CCCTCCACGGAGCAAACCTTAGGCAGGACGATTCTGTCAGAAACCTC

TTTGCCAGCGTCAAGAGTTCTCAGAGTTCCCCTATTATACCTGGCTTC

GGCGGGGATTTCAACCTGACACTACTTGAACCTGTAAGCATATCAAC

CGGAAGTCGCAGTGCCCGTTCCGCCATCGAGGATCTGCTCTTCGACA

AAGTAACTATTGCAGATCCCGGATACATGCAGGGGTATGACGACTG

CATGCAGCAGGGTCCAGCCTCTGCAAGGGATCTGATATGCGCACAG

TATGTCGCTGGGTACAAAGTGTTGCCTCCTCTCATGGACGTGAACAT

GGAAGCGGCCTATACCTCCTCACTTCTAGGCTCCATAGCGGGCGTGG

GATGGACCGCAGGGCTTTCAAGCTTCGCCGCAATTCCCTTTGCTCAA

TCTATCTTCTACAGGCTTAATGGCGTTGGAATCACCCAGCAGGTGTT

AAGCGAAAACCAGAAATTGATTGCCAATAAGTTTAACCAAGCTTTG

GGGGCCATGCAGACAGGCTTTACAACCACAAACGAGGCTTTCCATA

AAGTACAGGATGCGGTAAACAATAACGCACAAGCCCTGTCAAAGCT

GGCTTCAGAGCTCTCAAATACATTTGGCGCTATATCCGCGTCTATCG

GCGATATCATACAACGGTTGGACCCACCCGAACAGGACGCACAGAT

TGATCGTTTGATCAACGGGAGGCTTACCACCTTAAACGCTTTTGTGG

CCCAGCAACTGGTGCGGTCTGAGAGCGCCGCCTTGAGCGCTCAGCTG

GCAAAGGATAAAGTGAATGAATGCGTGAAAGCTCAATCAAAGAGAA

GTGGGTTTTGTGGGCAGGGTACTCATATTGTTTCCTTTGTGGTGAAC

GCCCCAAATGGACTCTACTTTATGCATGTTGGATACTACCCGAGCAA

CCACATCGAGGTCGTTTCCGCCTATGGGCTTTGTGACGCAGCAAACC

CTACTAACTGTATCGCGCCAGTTAATGGCTACTTTATTAAAACAAAT

AACACACGCATTGTGGATGAATGGAGTTACACAGGGTCCAGCTTCTA

CGCTCCAGAGCCTATCACCTCTCTGAACACAAAGTATGTGGCACCTC

AGGTCACATATCAGAACATCTCGACAAACCTGCCCCCCCCACTCTTG

GGCAACTCCACAGGGATCGACTTCCAGGACGAGCTTGACGAATTCTT

CAAGAACGTGTCCACCAGTATCCCTAATTTTGGTTCGCTGACCCAAA

TTAACACAACCCTGCTCGATCTGACATATGAAATGCTTTCACTACAG

CAGGTGGTCAAAGCGTTGAACGAGTCGTATATCGACCTGAAAGAGT

TAGGGAATTACACATACTATAACAAATGGCCCTGGTATATTTGGTTA

GGATTCATTGCCGGGCTGGTGGCCCTTGCCTTGTGCGTATTTTTCATC

TTGagcttctggatgtgctctaatgggtctctacagtgtagaatatgtattTGA

PDI-MERS-wtTMCT-AA(SEQ ID NO：106)

MAKNVAIFGLLFSLLVLVPSQIFAYVDVGPDSVKSACIEVDIQQTFFDKT

WPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHA

TGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRK

IYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRS

GNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTF

MYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVY

DTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAID

CGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSP

LLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNC

YSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNL

TTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDG

DYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVC

PKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYD

AYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEH

ISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLP

LGQSLCALPDTPSTLTPASVGSVPGEMRLASIAFNHPIQVDQLNSSYFKL

SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCS

KINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSIS

TGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQY

VAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIF

YRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDA

VNNNAQALSKLASELSNTFGAISASIGDIIQRLDPPEQDAQIDRLINGRLT

TLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIV

SFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYF

IKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLL

GNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVV

KALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILCCT

GCGTNCMGKLKCNRCCDRYEEYDLEPHKVHVH

PDI-MERS-H5iTMCT-AA(SEQ ID NO：107)

MAKNVAIFGLLFSLLVLVPSQIFAYVDVGPDSVKSACIEVDIQQTFFDKT

WPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHA

TGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRK

IYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRS

GNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTF

MYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVY

DTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAID

CGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSP

LLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNC

YSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNL

TTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDG

DYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVC

PKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYD

AYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEH

ISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLP

LGQSLCALPDTPSTLTPASVGSVPGEMRLASIAFNHPIQVDQLNSSYFKL

SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCS

KINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSIS

TGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQY

VAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIF

YRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDA

VNNNAQALSKLASELSNTFGAISASIGDIIQRLDPPEQDAQIDRLINGRLT

TLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIV

SFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYF

IKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLL

GNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVV

KALNESYIDLKELGNYTYYNKWPWYQILSIYSTVASSLALAIMMAGLSL

WMCSNGSLQCRICI

PDI-MERS-H5iCT-AA(SEQ ID NO：108)

MAKNVAIFGLLFSLLVLVPSQIFAYVDVGPDSVKSACIEVDIQQTFFDKT

WPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHA

TGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRK

IYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRS

GNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTF

MYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVY

DTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAID

CGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSP

LLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNC

YSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNL

TTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDG

DYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVC

PKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYD

AYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEH

ISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLP

LGQSLCALPDTPSTLTPASVGSVPGEMRLASIAFNHPIQVDQLNSSYFKL

SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCS

KINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSIS

TGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQY

VAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIF

YRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDA

VNNNAQALSKLASELSNTFGAISASIGDIIQRLDPPEQDAQIDRLINGRLT

TLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIV

SFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYF

IKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLL

GNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVV

KALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILSLW

MCSNGSLQCRICI

PDI-MERS-H5iCT(V4)-AA(SEQ ID NO：109)

MAKNVAIFGLLFSLLVLVPSQIFAYVDVGPDSVKSACIEVDIQQTFFDKT

WPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHA

TGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRK

IYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRS

GNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTF

MYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVY

DTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAID

CGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSP

LLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNC

YSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNL

TTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDG

DYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVC

PKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYD

AYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEH

ISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLP

LGQSLCALPDTPSTLTPASVGSVPGEMRLASIAFNHPIQVDQLNSSYFKL

SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCS

KINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSIS

TGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQY

VAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIF

YRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDA

VNNNAQALSKLASELSNTFGAISASIGDIIQRLDPPEQDAQIDRLINGRLT

TLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIV

SFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYF

IKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLL

GNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVV

KALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILCCSN

GSLQCRICI

PDI-MERS-H1cCT-AA(SEQ ID NO：110)

MAKNVAIFGLLFSLLVLVPSQIFAYVDVGPDSVKSACIEVDIQQTFFDKT

WPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHA

TGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRK

IYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRS

GNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTF

MYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVY

DTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAID

CGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSP

LLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNC

YSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNL

TTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDG

DYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVC

PKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYD

AYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEH

ISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLP

LGQSLCALPDTPSTLTPASVGSVPGEMRLASIAFNHPIQVDQLNSSYFKL

SIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCS

KINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSIS

TGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQY

VAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIF

YRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDA

VNNNAQALSKLASELSNTFGAISASIGDIIQRLDPPEQDAQIDRLINGRLT

TLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIV

SFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYF

IKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLL

GNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVV

KALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILSFW

MCSNGSLQCRICI

Cloning vector 7147 from left to right T-DNA (SEQ ID NO: 111)

tggcaggatatattgtggtgtaaacaaattgacgcttagacaacttaataacacattgcggacgtttttaatgtactg

aattaacgccgaatcccgggctggtatatttatatgttgtcaaataactcaaaaaccataaaagtttaagttagcaa

cattggtcaaaaacaatagagagagaaaaaggaagagggagaataaaaacataatgtgagtatgagagagaa

agttgtacaaaagttgtaccaaaatagttgtacaaatatcattgaggaatttgacaaaagctacacaaataagggtt

aattgctgtaaataaataaggatgacgcattagagagatgtaccattagagaatttttggcaagtcattaaaaaga

tcagttaactcatttttatatttcatagatcaaataagagaaataacggtatattaatccctccaaaaaaaaaaaacg

gtatatttactaaaaaatctaagccacgtaggaggataacaggatccccgtaggaggataacatccaatccaacc

aatcacaacaatcctgatgagataacccactttaagcccacgcatctgtggcacatctacattatctaaatcacac

attcttccacacatctgagccacacaaaaaccaatccacatctttatcacccattctataaaaaatcacactttgtga

gtctacactttgattcccttcaaacacatacaaagagaagagactaattaattaattaatcatcttgagagaaaatg

gaacgagctatacaaggaaacgacgctagggaacaagctaacagtgaacgttgggatggaggatcaggagg

taccacttctcccttcaaacttcctgacgaaagtccgagttggactgagtggcggctacataacgatgagacgaa

ttcgaatcaagataatccccttggtttcaaggaaagctggggtttcgggaaagttgtatttaagagatatctcagat

acgacaggacggaagcttcactgcacagagtccttggatcttggacgggagattcggttaactatgcagcatct

cgatttttcggtttcgaccagatcggatgtacctatagtattcggtttcgaggagttagtatcaccgtttctggaggg

tcgcgaactcttcagcatctctgtgagatggcaattcggtctaagcaagaactgctacagcttgccccaatcgaa

gtggaaagtaatgtatcaagaggatgccctgaaggtactcaaaccttcgaaaaagaaagcgagtaagttaaaat

aaatactatttgtatgagatgaactggtgtaatgtaattcatttacataagtggagtcagaatcagaatgtttcctcca

taactaactagacatgaagacctgccgcgtacaattgtcttatatttgaacaactaaaattgaacatcttttgccaca

actttataagtggttaatatagctcaaatatatggtcaagttcaatagattaataatggaaatatcagttatcgaaatt

gagcatgctcgcctaggagattgtcgtttcccgccttcagtttgcaagctgctctagccgtgtagccaatacgcaa

accgcctctccccgcgcgttgggaattactagcgcgtgtcgacaagcttgcatgccggtcaacatggtggagca

cgacacacttgtctactccaaaaatatcaaagatacagtctcagaagaccaaagggcaattgagacttttcaaca

aagggtaatatccggaaacctcctcggattccattgcccagctatctgtcactttattgtgaagatagtggaaaag

gaaggtggctcctacaaatgccatcattgcgataaaggaaaggccatcgttgaagatgcctctgccgacagtgg

tcccaaagatggacccccacccacgaggagcatcgtggaaaaagaagacgttccaaccacgtcttcaaagca

agtggattgatgtgataacatggtggagcacgacacacttgtctactccaaaaatatcaaagatacagtctcaga

agaccaaagggcaattgagacttttcaacaaagggtaatatccggaaacctcctcggattccattgcccagctat

ctgtcactttattgtgaagatagtggaaaaggaaggtggctcctacaaatgccatcattgcgataaaggaaaggc

catcgttgaagatgcctctgccgacagtggtcccaaagatggacccccacccacgaggagcatcgtggaaaaa

gaagacgttccaaccacgtcttcaaagcaagtggattgatgtgatatctccactgacgtaagggatgacgcaca

atcccactatccttcgcaagacccttcctctatataaggaagttcatttcatttggagaggcactccatttgaatctat

caaaccaaaacacattgagacgtcacgtactcctcagccaaaacgacacccccatctgtctatccactggcccc

tggatctgctgcccaaactaactccatggtgaccctgggatgcctggtcaagggctatttccctgagccagtgac

agtgacctggaactctggatccctgtccagcggtgtgcacaccttcccagctgtcctgcagtctgacctctacact

ctgagcagctcagtgactgtcccctccagcacctggcccagcgagaccgtcacctgcaacgttgcccacccgg

ccagcagcaccaaggtggacaagaaaattgtgcccagggattgtggttgtaagccttgcatatgtacagtccca

gaagtatcatctgtcttcatcttccccccaaagcccaaggatgtgctcaccattactctgactcctaaggtcacgtg

tgttgtggtagacatcagcaaggatgatcccgaggtccagttcagctggtttgtagatgatgtggaggtgcacac

agctcagacgcaaccccgggaggagcagttcaacagcactttccgctcagtcagtgaacttcccatcatgcacc

aggactggctcaatggcaaggagacgtccagattttggcgatctattcaactgtcgccagttcattggtactggta

gtctccctgggggcaatcagtttctggatgtgctctaatgggtctctacagtgtagaatatgtatttaaaggccttag

tcgtgtcgtttttcaaataatataatccttttagggttttagttagtttaaattttctgttgctcctgtttagcaggtcgtgc

cttcagcaagcacacaaaaacagagtgtttattttaagttgtttgtttagtgattcaaaaaaaaaatcgttcaaacatt

tggcaataaagtttcttaagattgaatcctgttgccggtcttgcgatgattatcatataatttctgttgaattacgttaa

gcatgtaataattaacatgtaatgcatgacgttatttatgagatgggtttttatgattagagtcccgcaattatacattt

aatacgcgatagaaaacaaaatatagcgcgcaaactaggataaattatcgcgcgcggtgtcatctatgttactag

atctctagagtctcaagcttggcgcgcccacgtgactagtggcactggccgtcgttttacaacgtcgtgactggg

aaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagag

gcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgctagagcagcttgagcttggatc

agattgtcgtttcccgccttcagtttaaactatcagtgtttgacaggatatattggcgggtaaacctaagagaaaag

agcgttta

Natural SARS-CoV-1S protein wtTM/CT AA P59594 (SEQ ID NO: 112) MFIFLLFLTLTSGSDLDRCTTFDDVQAPNYTQHTSSMRGVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYFAATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFFAVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVFKNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAFSPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAELKCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPSVYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNFNGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFGGVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNNVFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPTLKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEGKAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT

Natural MERS S protein wtTM/CT AA AFY13307 (SEQ ID NO: 113)

MIHSVFLLMFLLTPTESYVDVGPDSVKSACIEVDIQQTFFDKTWPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHATGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRKIYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRSGNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTFMYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVYDTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAIDCGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSPLLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNCYSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNLTTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDGDYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVCPKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYDAYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEHISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLPLGQSLCALPDTPSTLTPRSVRSVPGEMRLASIAFNHPIQVDQLNSSYFKLSIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCSKINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSISTGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQYVAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIFYRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDAVNNNAQALSKLASELSNTFGAISASIGDIIQRLDVLEQDAQIDRLINGRLTTLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIVSFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYFIKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLLGNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVVKALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILCCTGCGTNCMGKLKCNRCCDRYEEYDLEPHKVHVH

Natural SARS-CoV-1S protein wtTM/CT AA P59594, NO signal peptide (SEQ ID NO: 114)

SDLDRCTTFDDVQAPNYTQHTSSMRGVYYPDEIFRSDTLYLTQDLFLPFYSNVTGFHTINHTFGNPVIPFKDGIYFAATEKSNVVRGWVFGSTMNNKSQSVIIINNSTNVVIRACNFELCDNPFFAVSKPMGTQTHTMIFDNAFNCTFEYISDAFSLDVSEKSGNFKHLREFVFKNKDGFLYVYKGYQPIDVVRDLPSGFNTLKPIFKLPLGINITNFRAILTAFSPAQDIWGTSAAAYFVGYLKPTTFMLKYDENGTITDAVDCSQNPLAELKCSVKSFEIDKGIYQTSNFRVVPSGDVVRFPNITNLCPFGEVFNATKFPSVYAWERKKISNCVADYSVLYNSTFFSTFKCYGVSATKLNDLCFSNVYADSFVVKGDDVRQIAPGQTGVIADYNYKLPDDFMGCVLAWNTRNIDATSTGNYNYKYRYLRHGKLRPFERDISNVPFSPDGKPCTPPALNCYWPLNDYGFYTTTGIGYQPYRVVVLSFELLNAPATVCGPKLSTDLIKNQCVNFNFNGLTGTGVLTPSSKRFQPFQQFGRDVSDFTDSVRDPKTSEILDISPCSFGGVSVITPGTNASSEVAVLYQDVNCTDVSTAIHADQLTPAWRIYSTGNNVFQTQAGCLIGAEHVDTSYECDIPIGAGICASYHTVSLLRSTSQKSIVAYTMSLGADSSIAYSNNTIAIPTNFSISITTEVMPVSMAKTSVDCNMYICGDSTECANLLLQYGSFCTQLNRALSGIAAEQDRNTREVFAQVKQMYKTPTLKYFGGFNFSQILPDPLKPTKRSFIEDLLFNKVTLADAGFMKQYGECLGDINARDLICAQKFNGLTVLPPLLTDDMIAAYTAALVSGTATAGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKQIANQFNKAISQIQESLTTTSTALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQAAPHGVVFLHVTYVPSQERNFTTAPAICHEGKAYFPREGVFVFNGTSWFITQRNFFSPQIITTDNTFVSGNCDVVIGIINNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT

Natural MERS S protein wtTM/CT AA AFY13307, NO signal peptide (SEQ ID NO: 115) YVDVGPDSVKSACIEVDIQQTFFDKTWPRPIDVSKADGIIYPQGRTYSNITITYQGLFPYQGDHGDMYVYSAGHATGTTPQKLFVANYSQDVKQFANGFVVRIGAAANSTGTVIISPSTSATIRKIYPAFMLGSSVGNFSDGKMGRFFNHTLVLLPDGCGTLLRAFYCILEPRSGNHCPAGNSYTSFATYHTPATDCSDGNYNRNASLNSFKEYFNLRNCTFMYTYNITEDEILEWFGITQTAQGVHLFSSRYVDLYGGNMFQFATLPVYDTIKYYSIIPHSIRSIQSDRKAWAAFYVYKLQPLTFLLDFSVDGYIRRAIDCGFNDLSQLHCSYESFDVESGVYSVSSFEAKPSGSVVEQAEGVECDFSPLLSGTPPQVYNFKRLVFTNCNYNLTKLLSLFSVNDFTCSQISPAAIASNCYSSLILDYFSYPLSMKSDLSVSSAGPISQFNYKQSFSNPTCLILATVPHNLTTITKPLKYSYINKCSRFLSDDRTEVPQLVNANQYSPCVSIVPSTVWEDGDYYRKQLSPLEGGGWLVASGSTVAMTEQLQMGFGITVQYGTDTNSVCPKLEFANDTKIASQLGNCVEYSLYGVSGRGVFQNCTAVGVRQQRFVYDAYQNLVGYYSDDGNYYCLRACVSVPVSVIYDKETKTHATLFGSVACEHISSTMSQYSRSTRSMLKRRDSTYGPLQTPVGCVLGLVNSSLFVEDCKLPLGQSLCALPDTPSTLTPRSVRSVPGEMRLASIAFNHPIQVDQLNSSYFKLSIPTNFSFGVTQEYIQTTIQKVTVDCKQYVCNGFQKCEQLLREYGQFCSKINQALHGANLRQDDSVRNLFASVKSSQSSPIIPGFGGDFNLTLLEPVSISTGSRSARSAIEDLLFDKVTIADPGYMQGYDDCMQQGPASARDLICAQYVAGYKVLPPLMDVNMEAAYTSSLLGSIAGVGWTAGLSSFAAIPFAQSIFYRLNGVGITQQVLSENQKLIANKFNQALGAMQTGFTTTNEAFHKVQDAVNNNAQALSKLASELSNTFGAISASIGDIIQRLDVLEQDAQIDRLINGRLTTLNAFVAQQLVRSESAALSAQLAKDKVNECVKAQSKRSGFCGQGTHIVSFVVNAPNGLYFMHVGYYPSNHIEVVSAYGLCDAANPTNCIAPVNGYFIKTNNTRIVDEWSYTGSSFYAPEPITSLNTKYVAPQVTYQNISTNLPPPLLGNSTGIDFQDELDEFFKNVSTSIPNFGSLTQINTTLLDLTYEMLSLQQVVKALNESYIDLKELGNYTYYNKWPWYIWLGFIAGLVALALCVFFILCCTGCGTNCMGKLKCNRCCDRYEEYDLEPHKVHVH

Modified TMCT region of PDI-SARS-COV-1wtTMCT-AA (SEQ ID NO: 116)

WYVWLGFIAGLIAIVMVTILLCCMTSCCSCLKGACSCGSCCKFDEDDSEPVLKGVKLHYT

Modified TMCT region of PDI-SARS-COV-1H5iTMCT-AA (SEQ ID NO: 117)

WYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

Modified TMCT region of PDI-SARS-COV-1H5iCT-AA (SEQ ID NO: 118)

WYVWLGFIAGLIAIVMVTILLSLWMCSNGSLQCRICI

Modified TMCT region of PDI-SARS-COV-1H5iCT (V4) -AA (SEQ ID NO: 119)

WYVWLGFIAGLIAIVMVTILLCCSNGSLQCRICI

Modified TMCT region of PDI-SARS-COV-1H1cCT-AA (SEQ ID NO: 120)

WYVWLGFIAGLIAIVMVTILLSFWMCSNGSLQCRICI

Modified TMCT region of PDI-MERS-wtTMCT-AA (SEQ ID NO: 121)

WYIWLGFIAGLVALALCVFFILCCTGCGTNCMGKLKCNRCCDRYEEYDLEPHKVHVH

The TMCT region of modified PDI-MERS-H5iTMCT-AA (SEQ ID NO: 122)

WYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

The TMCT region of modified PDI-MERS-H5iCT-AA (SEQ ID NO: 123)

WYIWLGFIAGLVALALCVFFILSLWMCSNGSLQCRICI

The TMCT region of modified PDI-MERS-H5iCT (V4) -AA (SEQ ID NO: 124)

WYIWLGFIAGLVALALCVFFILCCSNGSLQCRICI

Modified TMCT region of PDI-MERS-H1cCT-AA (SEQ ID NO: 125)

WYIWLGFIAGLVALALCVFFILSFWMCSNGSLQCRICI

Modified PDI-S protein+H2 Cal TMCT region (SEQ ID NO: 126)

WYIWLGFIAGLIAIVMVTIMLSFWMCSNGSLQCRICI

Modified PDI-S protein+H2 Minn TMCT region (SEQ ID NO: 127)

WYIWLGFIAGLIAIVMVTIMLMWACQKGNIRCNICI

The TMCT region of modified PDI-S protein +H2HK (SEQ ID NO: 128)

WYIWLGFIAGLIAIVMVTIMLGLWMCSNGSMQCRICI

Modified PDI-S protein+H27 Guangdong TMCT region (SEQ ID NO: 129)

WYIWLGFIAGLIAIVMVTIMLVFICVKNGNMRCTICI

The TMCT region of modified PDI-S protein +H2HK (SEQ ID NO: 130)

WYIWLGFIAGLIAIVMVTIMLLFWAMSNGSCRCNICI

Modified TMCT region of PDI-S protein+B/Wash (SEQ ID NO: 131)

WYIWLGFIAGLIAIVMVTIMLVVYMVSRDNVSCSICL

Consensus sequence of the TM domain of the coronavirus S protein (SEQ ID NO: 132)

WYXWLGFIAGLXAXXX { X } VXXL ({ X } may not be present)

Consensus sequence of the TM domain of the coronavirus S protein (SEQ ID NO: 133)

WY [ I/V ] WLGFIAGL [ V/I ] A [ L/I ] [ A/V ] [ L/M ] { X } V [ F/T ] [ F/I ] XL (wherein { X } may be C or absent)

The TM/CT region of the modified SARS-CoV-1S protein has the intermediate peptide sequence Xn (SEQ ID NO: 134)

WYVWLGFIAGLIAIVMVTIL-(X)n-CSNGSXXCXICI

Modified MERS S protein TM/CT region with intermediate peptide sequence Xn (SEQ ID NO: 135)

WYIWLGFIAGLVALALCVFFIL-(X)n–csngsXXCXICI

IF(AvB+wtCT-OC43).r(SEQ ID NO：136)

ACGACACGACTAAGGCCTTCAGTCGTCATGCGAGGTCTTAATGACAAGC

PDI-OC43-wtTMCT-DNA(SEQ ID NO：137)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgGTGATCGGCGATCTGAATTGTACCCTGGATCCCCGCCTGAAAGGGAGCTTTAACAACCGAGATACAGGACCCCCGTCTATATCCATAGATACAGTGGATGTTACGAACGGGCTCGGCACCTACTATGTGCTAGACCGAGTTTATTTGAACACCACCTTATTCCTCAATGGATACTACCCAACTTCAGGTAGTACTTACAGAAACATGGCGCTGAAGGGTACGGATCTGCTGAGCACCCTATGGTTTAAACCTCCCTTCCTCTCGGACTTTATTAATGGCATCTTCGCTAAGGTGAAAAACACGAAGGTTTTCAAAGATGGAGTGATGTATTC

AGAGTTCCCTGCGATCACCATTGGAAGTACCTTCGTGAATACTTCCT

ATAGCGTGGTGGTTCAACCACGGACAATCAACTCCACCCAGGACGG

CGTCAACAAGCTCCAGGGATTGCTGGAGGTGTCAGTCTGTCAATATA

ACATGTGTGAGTACCCACACACTATCTGTCACCCTAATCTAGGCAAC

CACTTTAAGGAACTGTGGCACTACGATACGGGGGTGGTAAGTTGCTT

ATATAAGAGAAATTTCACCTATGATGTTAATGCAACGTACCTGTACT

TTCACTTCTATCAAGAAGGAGGAACTTTCTACGCATATTTCACAGAT

ACCGGCTTTGTGACGAAATTCTTATTCAACGTTTACCTCGGAATGGC

ATTAAGCCATTATTACGTGATGCCTCTCACTTGCATCAGACGCCCTA

AGGATGGTTTTTCTCTGGAGTACTGGGTCACTCCCCTGACACCACGG

CAGTACCTGCTTGCTTTTAACCAGGACGGTATCATTTTTAATGCCGTC

GATTGTATGAGCGATTTTATGAGCGAGATAAAGTGCAAGACCCAAT

CTATTGCTCCGCCCACGGGGGTGTACGAACTGAATGGTTACACCGTC

CAGCCCGTTGCCGATGTATATAGACGGAAACCAGACCTGCCCAATTG

CAACATCGAAGCTTGGTTAAACGATAAGTCAGTGCCCTCCCCCCTCA

ATTGGGAGAGGAAGACTTTCTCCAACTGTAATTTCAACATGTCAAGC

CTGATGTCTTTCATTCAAGCCGATTCGTTCACTTGTAATAATATAGAT

GCAGCAAAGATCTATGGTATGTGCTTCAGTTCCATCACAATAGATAA

GTTTGCAATACCAAACCGTCGCAAGGTGGACCTTCAGCTCGGCAACC

TGGGCTATCTGCAGTCCAGCAATTATAGAATAGACACCACCGCCACA

TCATGTCAGCTGTACTATAACCTCCCAGCAGCGAACGTCAGTGTTAG

TAGGTTCAATCCTTCTACCTGGAATAAAAGGTTTGGATTCATCGAAG

ATAGTGTGTTCGTACCTCAGCCAACAGGAGTGTTCACCAATCACAGC

GTGGTCTACGCCCAACATTGCTTCAAGGCACCCAAAAATTTCTGCCC

ATGTAGCAGTTGCTCCTGCCCGGGTAAGAACAATGGGATCGGCACCT

GCCCAGCAGGCACCAATTCACTTACATGCGATAATCTGTGTACACTG

GATCCTATTACACTTAAGGCCCCTGATACCTACAAATGCCCCCAGAG

CAAGAGCCTGGTCGGTATCGGAGAACACTGTTCCGGACTTGCAGTA

AAAAGCGACTATTGTGGAAATAACTCTTGCACTTGTCAGCCACAAGC

CTTCCTCGGTTGGTCCGCTGACTCTTGTTTACAAGGGGATAAGTGTA

ACATCTTCGCAAATTTCATCTTACACGATGTGAATAACGGCTTAACA

TGCAGCACAGATCTCCAGAAGGCAAACACAGAGATCGAATTAGGAG

TCTGCGTTAATTACGATCTCTACGGGATCTCTGGCCAGGGCATCTTC

GTGGAGGTTAATGCTACCTACTACAATAGTTGGCAAAATCTGCTCTA

CGATAGCAATGGCAACCTCTATGGATTCAGAGACTATATTACTAACA

GGACGTTCATGATTCACTCGTGCTATTCCGGGCGGGTGTCAGCAGCT

TATCACGCAAATTCTTCAGAGCCAGCTCTGCTATTCCGAAACATAAA

ATGTAATTACGTGTTCAATAATTCACTGACTCGGCAGCTGCAGCCGA

TTAATTACAGCTTCGACAGCTACCTTGGTTGCGTTGTTAACGCCTAC

AACTCCACTGCCATATCAGTTCAGACCTGCGACCTTACTGTGGGCTC

TGGCTATTGTGTCGATTATTCAAAGAACGGGGGGAGCGGGTCCGCA

ATAACAACTGGCTATAGGTTCACCAATTTTGAGCCTTTCACCGTGAA

TAGTGTCAACGATAGCCTGGAGCCTGTCGGAGGTCTTTATGAGATAC

AAATCCCCTCCGAGTTCACAATTGGCAACATGGAAGAGTTCATCCAG

ACGAGTTCCCCAAAGGTGACGATCGATTGCGCGGCTTTCGTCTGCGG

CGACTACGCCGCATGCAAGTTACAACTCGTTGAGTATGGAAGTTTTT

GCGATAATATAAACGCAATTCTGACTGAAGTGAACGAACTGCTGGA

CACCACTCAGTTGCAGGTGGCAAATTCGCTCATGAACGGCGTGACAC

TGTCAACCAAACTGAAGGACGGTGTCAATTTCAATGTGGATGACATT

AACTTCAGCCCCGTACTGGGCTGTTTGGGTAGTGAGTGTTCTAAGGC

TAGCAGCCGCTCCGCCATTGAGGACTTGTTGTTTGATAAAGTTAAGC

TGAGTGACGTTGGATTTGTTGAGGCGTATAATAACTGTACCGGTGGT

GCAGAGATAAGGGATCTGATCTGTGTCCAGAGTTATAAGGGGATTA

AGGTTCTCCCCCCGCTACTCTCGGAGAATCAGATATCAGGATACACC

CTGGCCGCTACCTCAGCCTCGCTGTTTCCCCCTTGGACCGCTGCCGCC

GGTGTCCCATTTTATTTGAATGTGCAGTATCGGATCAACGGTCTGGG

AGTGACAATGGACGTGCTGTCTCAGAACCAGAAACTGATCGCCAAT

GCATTCAACAATGCTCTGCACGCCATCCAGCAAGGGTTTGACGCTAC

AAATTCTGCCCTCGTAAAAATCCAGGCCGTGGTGAATGCTAACGCCG

AAGCCCTTAATAATCTGCTCCAGCAGCTTTCTAACCGCTTTGGAGCT

ATTTCTGCCTCACTGCAGGAAATTCTATCCAGACTGGATCCCCCTGA

GGCAGAAGCCCAAATCGACCGTCTCATAAACGGCAGACTCACTGCT

CTTAACGCCTACGTTAGTCAACAATTGAGCGATTCGACCTTGGTGAA

ATTCAGCGCAGCTCAGGCTATGGAGAAGGTGAACGAGTGCGTGAAG

TCACAGAGCTCCAGAATCAATTTCTGTGGCAATGGGAACCATATCAT

CTCCTTGGTTCAGAATGCTCCCTACGGCCTGTATTTCATCCACTTCAA

CTACGTGCCCACGAAGTACGTTACAGCCAAAGTGTCCCCCGGACTGT

GCATCGCTGGTAACAGGGGCATTGCACCAAAATCCGGCTACTTCGTC

AATGTCAACAACACATGGATGTATACTGGGAGTGGTTATTATTACCC

TGAACCTATAACAGAGAACAATGTAGTAGTCATGTCCACATGCGCC

GTCAATTATACTAAGGCCCCCTATGTTATGCTCAACACTTCAATTCCC

AATCTCCCGGATTTCAAAGAAGAGCTGGATCAGTGGTTTAAGAATCA

GACATCCGTGGCCCCTGACTTAAGCTTGGATTATATCAATGTGACTT

TTTTAGACTTACAGGTCGAGATGAACCGACTCCAGGAAGCTATAAA

AGTACTGAACCACTCCTATATCAATCTGAAAGATATCGGTACATACG

AATATTACGTAAAATGGCCTTGGTATGTGTGGCTACTAATTTGCCTT

GCGGGCGTGGCTATGCTGGTCCTGCTGTTCTTCATTTGCTGCTGTACT

GGGTGCGGTACTTCCTGCTTCAAAAAGTGCGGTGGTTGCTGCGACGA

CTACACTGGGTACCAGGAGCTTGTCATTAAGACCTCGCATGACGACT

GA

PDI-OC43-H5iTMCT-DNA(SEQ ID NO：138)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgGTGAT

CGGCGATCTGAATTGTACCCTGGATCCCCGCCTGAAAGGGAGCTTTA

ACAACCGAGATACAGGACCCCCGTCTATATCCATAGATACAGTGGA

TGTTACGAACGGGCTCGGCACCTACTATGTGCTAGACCGAGTTTATT

TGAACACCACCTTATTCCTCAATGGATACTACCCAACTTCAGGTAGT

ACTTACAGAAACATGGCGCTGAAGGGTACGGATCTGCTGAGCACCC

TATGGTTTAAACCTCCCTTCCTCTCGGACTTTATTAATGGCATCTTCG

CTAAGGTGAAAAACACGAAGGTTTTCAAAGATGGAGTGATGTATTC

AGAGTTCCCTGCGATCACCATTGGAAGTACCTTCGTGAATACTTCCT

ATAGCGTGGTGGTTCAACCACGGACAATCAACTCCACCCAGGACGG

CGTCAACAAGCTCCAGGGATTGCTGGAGGTGTCAGTCTGTCAATATA

ACATGTGTGAGTACCCACACACTATCTGTCACCCTAATCTAGGCAAC

CACTTTAAGGAACTGTGGCACTACGATACGGGGGTGGTAAGTTGCTT

ATATAAGAGAAATTTCACCTATGATGTTAATGCAACGTACCTGTACT

TTCACTTCTATCAAGAAGGAGGAACTTTCTACGCATATTTCACAGAT

ACCGGCTTTGTGACGAAATTCTTATTCAACGTTTACCTCGGAATGGC

ATTAAGCCATTATTACGTGATGCCTCTCACTTGCATCAGACGCCCTA

AGGATGGTTTTTCTCTGGAGTACTGGGTCACTCCCCTGACACCACGG

CAGTACCTGCTTGCTTTTAACCAGGACGGTATCATTTTTAATGCCGTC

GATTGTATGAGCGATTTTATGAGCGAGATAAAGTGCAAGACCCAAT

CTATTGCTCCGCCCACGGGGGTGTACGAACTGAATGGTTACACCGTC

CAGCCCGTTGCCGATGTATATAGACGGAAACCAGACCTGCCCAATTG

CAACATCGAAGCTTGGTTAAACGATAAGTCAGTGCCCTCCCCCCTCA

ATTGGGAGAGGAAGACTTTCTCCAACTGTAATTTCAACATGTCAAGC

CTGATGTCTTTCATTCAAGCCGATTCGTTCACTTGTAATAATATAGAT

GCAGCAAAGATCTATGGTATGTGCTTCAGTTCCATCACAATAGATAA

GTTTGCAATACCAAACCGTCGCAAGGTGGACCTTCAGCTCGGCAACC

TGGGCTATCTGCAGTCCAGCAATTATAGAATAGACACCACCGCCACA

TCATGTCAGCTGTACTATAACCTCCCAGCAGCGAACGTCAGTGTTAG

TAGGTTCAATCCTTCTACCTGGAATAAAAGGTTTGGATTCATCGAAG

ATAGTGTGTTCGTACCTCAGCCAACAGGAGTGTTCACCAATCACAGC

GTGGTCTACGCCCAACATTGCTTCAAGGCACCCAAAAATTTCTGCCC

ATGTAGCAGTTGCTCCTGCCCGGGTAAGAACAATGGGATCGGCACCT

GCCCAGCAGGCACCAATTCACTTACATGCGATAATCTGTGTACACTG

GATCCTATTACACTTAAGGCCCCTGATACCTACAAATGCCCCCAGAG

CAAGAGCCTGGTCGGTATCGGAGAACACTGTTCCGGACTTGCAGTA

AAAAGCGACTATTGTGGAAATAACTCTTGCACTTGTCAGCCACAAGC

CTTCCTCGGTTGGTCCGCTGACTCTTGTTTACAAGGGGATAAGTGTA

ACATCTTCGCAAATTTCATCTTACACGATGTGAATAACGGCTTAACA

TGCAGCACAGATCTCCAGAAGGCAAACACAGAGATCGAATTAGGAG

TCTGCGTTAATTACGATCTCTACGGGATCTCTGGCCAGGGCATCTTC

GTGGAGGTTAATGCTACCTACTACAATAGTTGGCAAAATCTGCTCTA

CGATAGCAATGGCAACCTCTATGGATTCAGAGACTATATTACTAACA

GGACGTTCATGATTCACTCGTGCTATTCCGGGCGGGTGTCAGCAGCT

TATCACGCAAATTCTTCAGAGCCAGCTCTGCTATTCCGAAACATAAA

ATGTAATTACGTGTTCAATAATTCACTGACTCGGCAGCTGCAGCCGA

TTAATTACAGCTTCGACAGCTACCTTGGTTGCGTTGTTAACGCCTAC

AACTCCACTGCCATATCAGTTCAGACCTGCGACCTTACTGTGGGCTC

TGGCTATTGTGTCGATTATTCAAAGAACGGGGGGAGCGGGTCCGCA

ATAACAACTGGCTATAGGTTCACCAATTTTGAGCCTTTCACCGTGAA

TAGTGTCAACGATAGCCTGGAGCCTGTCGGAGGTCTTTATGAGATAC

AAATCCCCTCCGAGTTCACAATTGGCAACATGGAAGAGTTCATCCAG

ACGAGTTCCCCAAAGGTGACGATCGATTGCGCGGCTTTCGTCTGCGG

CGACTACGCCGCATGCAAGTTACAACTCGTTGAGTATGGAAGTTTTT

GCGATAATATAAACGCAATTCTGACTGAAGTGAACGAACTGCTGGA

CACCACTCAGTTGCAGGTGGCAAATTCGCTCATGAACGGCGTGACAC

TGTCAACCAAACTGAAGGACGGTGTCAATTTCAATGTGGATGACATT

AACTTCAGCCCCGTACTGGGCTGTTTGGGTAGTGAGTGTTCTAAGGC

TAGCAGCCGCTCCGCCATTGAGGACTTGTTGTTTGATAAAGTTAAGC

TGAGTGACGTTGGATTTGTTGAGGCGTATAATAACTGTACCGGTGGT

GCAGAGATAAGGGATCTGATCTGTGTCCAGAGTTATAAGGGGATTA

AGGTTCTCCCCCCGCTACTCTCGGAGAATCAGATATCAGGATACACC

CTGGCCGCTACCTCAGCCTCGCTGTTTCCCCCTTGGACCGCTGCCGCC

GGTGTCCCATTTTATTTGAATGTGCAGTATCGGATCAACGGTCTGGG

AGTGACAATGGACGTGCTGTCTCAGAACCAGAAACTGATCGCCAAT

GCATTCAACAATGCTCTGCACGCCATCCAGCAAGGGTTTGACGCTAC

AAATTCTGCCCTCGTAAAAATCCAGGCCGTGGTGAATGCTAACGCCG

AAGCCCTTAATAATCTGCTCCAGCAGCTTTCTAACCGCTTTGGAGCT

ATTTCTGCCTCACTGCAGGAAATTCTATCCAGACTGGATCCCCCTGA

GGCAGAAGCCCAAATCGACCGTCTCATAAACGGCAGACTCACTGCT

CTTAACGCCTACGTTAGTCAACAATTGAGCGATTCGACCTTGGTGAA

ATTCAGCGCAGCTCAGGCTATGGAGAAGGTGAACGAGTGCGTGAAG

TCACAGAGCTCCAGAATCAATTTCTGTGGCAATGGGAACCATATCAT

CTCCTTGGTTCAGAATGCTCCCTACGGCCTGTATTTCATCCACTTCAA

CTACGTGCCCACGAAGTACGTTACAGCCAAAGTGTCCCCCGGACTGT

GCATCGCTGGTAACAGGGGCATTGCACCAAAATCCGGCTACTTCGTC

AATGTCAACAACACATGGATGTATACTGGGAGTGGTTATTATTACCC

TGAACCTATAACAGAGAACAATGTAGTAGTCATGTCCACATGCGCC

GTCAATTATACTAAGGCCCCCTATGTTATGCTCAACACTTCAATTCCC

AATCTCCCGGATTTCAAAGAAGAGCTGGATCAGTGGTTTAAGAATCA

GACATCCGTGGCCCCTGACTTAAGCTTGGATTATATCAATGTGACTT

TTTTAGACTTACAGGTCGAGATGAACCGACTCCAGGAAGCTATAAA

AGTACTGAACCACTCCTATATCAATCTGAAAGATATCGGTACATACG

AATATTACGTAAAATGGCCTTGGTATcaaatactgtcaatttattcaacagtggcgagttc

cctagcactggcaatcatgatggctggtctatctttatggatgtgctccaatggatcgttacaatgcagaatttgcat

tTGA

PDI-OC43-H5iCT-DNA(SEQ ID NO：139)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgGTGAT

CGGCGATCTGAATTGTACCCTGGATCCCCGCCTGAAAGGGAGCTTTA

ACAACCGAGATACAGGACCCCCGTCTATATCCATAGATACAGTGGA

TGTTACGAACGGGCTCGGCACCTACTATGTGCTAGACCGAGTTTATT

TGAACACCACCTTATTCCTCAATGGATACTACCCAACTTCAGGTAGT

ACTTACAGAAACATGGCGCTGAAGGGTACGGATCTGCTGAGCACCC

TATGGTTTAAACCTCCCTTCCTCTCGGACTTTATTAATGGCATCTTCG

CTAAGGTGAAAAACACGAAGGTTTTCAAAGATGGAGTGATGTATTC

AGAGTTCCCTGCGATCACCATTGGAAGTACCTTCGTGAATACTTCCT

ATAGCGTGGTGGTTCAACCACGGACAATCAACTCCACCCAGGACGG

CGTCAACAAGCTCCAGGGATTGCTGGAGGTGTCAGTCTGTCAATATA

ACATGTGTGAGTACCCACACACTATCTGTCACCCTAATCTAGGCAAC

CACTTTAAGGAACTGTGGCACTACGATACGGGGGTGGTAAGTTGCTT

ATATAAGAGAAATTTCACCTATGATGTTAATGCAACGTACCTGTACT

TTCACTTCTATCAAGAAGGAGGAACTTTCTACGCATATTTCACAGAT

ACCGGCTTTGTGACGAAATTCTTATTCAACGTTTACCTCGGAATGGC

ATTAAGCCATTATTACGTGATGCCTCTCACTTGCATCAGACGCCCTA

AGGATGGTTTTTCTCTGGAGTACTGGGTCACTCCCCTGACACCACGG

CAGTACCTGCTTGCTTTTAACCAGGACGGTATCATTTTTAATGCCGTC

GATTGTATGAGCGATTTTATGAGCGAGATAAAGTGCAAGACCCAAT

CTATTGCTCCGCCCACGGGGGTGTACGAACTGAATGGTTACACCGTC

CAGCCCGTTGCCGATGTATATAGACGGAAACCAGACCTGCCCAATTG

CAACATCGAAGCTTGGTTAAACGATAAGTCAGTGCCCTCCCCCCTCA

ATTGGGAGAGGAAGACTTTCTCCAACTGTAATTTCAACATGTCAAGC

CTGATGTCTTTCATTCAAGCCGATTCGTTCACTTGTAATAATATAGAT

GCAGCAAAGATCTATGGTATGTGCTTCAGTTCCATCACAATAGATAA

GTTTGCAATACCAAACCGTCGCAAGGTGGACCTTCAGCTCGGCAACC

TGGGCTATCTGCAGTCCAGCAATTATAGAATAGACACCACCGCCACA

TCATGTCAGCTGTACTATAACCTCCCAGCAGCGAACGTCAGTGTTAG

TAGGTTCAATCCTTCTACCTGGAATAAAAGGTTTGGATTCATCGAAG

ATAGTGTGTTCGTACCTCAGCCAACAGGAGTGTTCACCAATCACAGC

GTGGTCTACGCCCAACATTGCTTCAAGGCACCCAAAAATTTCTGCCC

ATGTAGCAGTTGCTCCTGCCCGGGTAAGAACAATGGGATCGGCACCT

GCCCAGCAGGCACCAATTCACTTACATGCGATAATCTGTGTACACTG

GATCCTATTACACTTAAGGCCCCTGATACCTACAAATGCCCCCAGAG

CAAGAGCCTGGTCGGTATCGGAGAACACTGTTCCGGACTTGCAGTA

AAAAGCGACTATTGTGGAAATAACTCTTGCACTTGTCAGCCACAAGC

CTTCCTCGGTTGGTCCGCTGACTCTTGTTTACAAGGGGATAAGTGTA

ACATCTTCGCAAATTTCATCTTACACGATGTGAATAACGGCTTAACA

TGCAGCACAGATCTCCAGAAGGCAAACACAGAGATCGAATTAGGAG

TCTGCGTTAATTACGATCTCTACGGGATCTCTGGCCAGGGCATCTTC

GTGGAGGTTAATGCTACCTACTACAATAGTTGGCAAAATCTGCTCTA

CGATAGCAATGGCAACCTCTATGGATTCAGAGACTATATTACTAACA

GGACGTTCATGATTCACTCGTGCTATTCCGGGCGGGTGTCAGCAGCT

TATCACGCAAATTCTTCAGAGCCAGCTCTGCTATTCCGAAACATAAA

ATGTAATTACGTGTTCAATAATTCACTGACTCGGCAGCTGCAGCCGA

TTAATTACAGCTTCGACAGCTACCTTGGTTGCGTTGTTAACGCCTAC

AACTCCACTGCCATATCAGTTCAGACCTGCGACCTTACTGTGGGCTC

TGGCTATTGTGTCGATTATTCAAAGAACGGGGGGAGCGGGTCCGCA

ATAACAACTGGCTATAGGTTCACCAATTTTGAGCCTTTCACCGTGAA

TAGTGTCAACGATAGCCTGGAGCCTGTCGGAGGTCTTTATGAGATAC

AAATCCCCTCCGAGTTCACAATTGGCAACATGGAAGAGTTCATCCAG

ACGAGTTCCCCAAAGGTGACGATCGATTGCGCGGCTTTCGTCTGCGG

CGACTACGCCGCATGCAAGTTACAACTCGTTGAGTATGGAAGTTTTT

GCGATAATATAAACGCAATTCTGACTGAAGTGAACGAACTGCTGGA

CACCACTCAGTTGCAGGTGGCAAATTCGCTCATGAACGGCGTGACAC

TGTCAACCAAACTGAAGGACGGTGTCAATTTCAATGTGGATGACATT

AACTTCAGCCCCGTACTGGGCTGTTTGGGTAGTGAGTGTTCTAAGGC

TAGCAGCCGCTCCGCCATTGAGGACTTGTTGTTTGATAAAGTTAAGC

TGAGTGACGTTGGATTTGTTGAGGCGTATAATAACTGTACCGGTGGT

GCAGAGATAAGGGATCTGATCTGTGTCCAGAGTTATAAGGGGATTA

AGGTTCTCCCCCCGCTACTCTCGGAGAATCAGATATCAGGATACACC

CTGGCCGCTACCTCAGCCTCGCTGTTTCCCCCTTGGACCGCTGCCGCC

GGTGTCCCATTTTATTTGAATGTGCAGTATCGGATCAACGGTCTGGG

AGTGACAATGGACGTGCTGTCTCAGAACCAGAAACTGATCGCCAAT

GCATTCAACAATGCTCTGCACGCCATCCAGCAAGGGTTTGACGCTAC

AAATTCTGCCCTCGTAAAAATCCAGGCCGTGGTGAATGCTAACGCCG

AAGCCCTTAATAATCTGCTCCAGCAGCTTTCTAACCGCTTTGGAGCT

ATTTCTGCCTCACTGCAGGAAATTCTATCCAGACTGGATCCCCCTGA

GGCAGAAGCCCAAATCGACCGTCTCATAAACGGCAGACTCACTGCT

CTTAACGCCTACGTTAGTCAACAATTGAGCGATTCGACCTTGGTGAA

ATTCAGCGCAGCTCAGGCTATGGAGAAGGTGAACGAGTGCGTGAAG

TCACAGAGCTCCAGAATCAATTTCTGTGGCAATGGGAACCATATCAT

CTCCTTGGTTCAGAATGCTCCCTACGGCCTGTATTTCATCCACTTCAA

CTACGTGCCCACGAAGTACGTTACAGCCAAAGTGTCCCCCGGACTGT

GCATCGCTGGTAACAGGGGCATTGCACCAAAATCCGGCTACTTCGTC

AATGTCAACAACACATGGATGTATACTGGGAGTGGTTATTATTACCC

TGAACCTATAACAGAGAACAATGTAGTAGTCATGTCCACATGCGCC

GTCAATTATACTAAGGCCCCCTATGTTATGCTCAACACTTCAATTCCC

AATCTCCCGGATTTCAAAGAAGAGCTGGATCAGTGGTTTAAGAATCA

GACATCCGTGGCCCCTGACTTAAGCTTGGATTATATCAATGTGACTT

TTTTAGACTTACAGGTCGAGATGAACCGACTCCAGGAAGCTATAAA

AGTACTGAACCACTCCTATATCAATCTGAAAGATATCGGTACATACG

AATATTACGTAAAATGGCCTTGGTATGTGTGGCTACTAATTTGCCTT

GCGGGCGTGGCTATGCTGGTCCTGCTGTTCTTCATTtctttatggatgtgctccaa

tggatcgttacaatgcagaatttgcattTGA

PDI-OC43-H5iCT(V4)-DNA(SEQ ID NO：140)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgGTGAT

CGGCGATCTGAATTGTACCCTGGATCCCCGCCTGAAAGGGAGCTTTA

ACAACCGAGATACAGGACCCCCGTCTATATCCATAGATACAGTGGA

TGTTACGAACGGGCTCGGCACCTACTATGTGCTAGACCGAGTTTATT

TGAACACCACCTTATTCCTCAATGGATACTACCCAACTTCAGGTAGT

ACTTACAGAAACATGGCGCTGAAGGGTACGGATCTGCTGAGCACCC

TATGGTTTAAACCTCCCTTCCTCTCGGACTTTATTAATGGCATCTTCG

CTAAGGTGAAAAACACGAAGGTTTTCAAAGATGGAGTGATGTATTC

AGAGTTCCCTGCGATCACCATTGGAAGTACCTTCGTGAATACTTCCT

ATAGCGTGGTGGTTCAACCACGGACAATCAACTCCACCCAGGACGG

CGTCAACAAGCTCCAGGGATTGCTGGAGGTGTCAGTCTGTCAATATA

ACATGTGTGAGTACCCACACACTATCTGTCACCCTAATCTAGGCAAC

CACTTTAAGGAACTGTGGCACTACGATACGGGGGTGGTAAGTTGCTT

ATATAAGAGAAATTTCACCTATGATGTTAATGCAACGTACCTGTACT

TTCACTTCTATCAAGAAGGAGGAACTTTCTACGCATATTTCACAGAT

ACCGGCTTTGTGACGAAATTCTTATTCAACGTTTACCTCGGAATGGC

ATTAAGCCATTATTACGTGATGCCTCTCACTTGCATCAGACGCCCTA

AGGATGGTTTTTCTCTGGAGTACTGGGTCACTCCCCTGACACCACGG

CAGTACCTGCTTGCTTTTAACCAGGACGGTATCATTTTTAATGCCGTC

GATTGTATGAGCGATTTTATGAGCGAGATAAAGTGCAAGACCCAAT

CTATTGCTCCGCCCACGGGGGTGTACGAACTGAATGGTTACACCGTC

CAGCCCGTTGCCGATGTATATAGACGGAAACCAGACCTGCCCAATTG

CAACATCGAAGCTTGGTTAAACGATAAGTCAGTGCCCTCCCCCCTCA

ATTGGGAGAGGAAGACTTTCTCCAACTGTAATTTCAACATGTCAAGC

CTGATGTCTTTCATTCAAGCCGATTCGTTCACTTGTAATAATATAGAT

GCAGCAAAGATCTATGGTATGTGCTTCAGTTCCATCACAATAGATAA

GTTTGCAATACCAAACCGTCGCAAGGTGGACCTTCAGCTCGGCAACC

TGGGCTATCTGCAGTCCAGCAATTATAGAATAGACACCACCGCCACA

TCATGTCAGCTGTACTATAACCTCCCAGCAGCGAACGTCAGTGTTAG

TAGGTTCAATCCTTCTACCTGGAATAAAAGGTTTGGATTCATCGAAG

ATAGTGTGTTCGTACCTCAGCCAACAGGAGTGTTCACCAATCACAGC

GTGGTCTACGCCCAACATTGCTTCAAGGCACCCAAAAATTTCTGCCC

ATGTAGCAGTTGCTCCTGCCCGGGTAAGAACAATGGGATCGGCACCT

GCCCAGCAGGCACCAATTCACTTACATGCGATAATCTGTGTACACTG

GATCCTATTACACTTAAGGCCCCTGATACCTACAAATGCCCCCAGAG

CAAGAGCCTGGTCGGTATCGGAGAACACTGTTCCGGACTTGCAGTA

AAAAGCGACTATTGTGGAAATAACTCTTGCACTTGTCAGCCACAAGC

CTTCCTCGGTTGGTCCGCTGACTCTTGTTTACAAGGGGATAAGTGTA

ACATCTTCGCAAATTTCATCTTACACGATGTGAATAACGGCTTAACA

TGCAGCACAGATCTCCAGAAGGCAAACACAGAGATCGAATTAGGAG

TCTGCGTTAATTACGATCTCTACGGGATCTCTGGCCAGGGCATCTTC

GTGGAGGTTAATGCTACCTACTACAATAGTTGGCAAAATCTGCTCTA

CGATAGCAATGGCAACCTCTATGGATTCAGAGACTATATTACTAACA

GGACGTTCATGATTCACTCGTGCTATTCCGGGCGGGTGTCAGCAGCT

TATCACGCAAATTCTTCAGAGCCAGCTCTGCTATTCCGAAACATAAA

ATGTAATTACGTGTTCAATAATTCACTGACTCGGCAGCTGCAGCCGA

TTAATTACAGCTTCGACAGCTACCTTGGTTGCGTTGTTAACGCCTAC

AACTCCACTGCCATATCAGTTCAGACCTGCGACCTTACTGTGGGCTC

TGGCTATTGTGTCGATTATTCAAAGAACGGGGGGAGCGGGTCCGCA

ATAACAACTGGCTATAGGTTCACCAATTTTGAGCCTTTCACCGTGAA

TAGTGTCAACGATAGCCTGGAGCCTGTCGGAGGTCTTTATGAGATAC

AAATCCCCTCCGAGTTCACAATTGGCAACATGGAAGAGTTCATCCAG

ACGAGTTCCCCAAAGGTGACGATCGATTGCGCGGCTTTCGTCTGCGG

CGACTACGCCGCATGCAAGTTACAACTCGTTGAGTATGGAAGTTTTT

GCGATAATATAAACGCAATTCTGACTGAAGTGAACGAACTGCTGGA

CACCACTCAGTTGCAGGTGGCAAATTCGCTCATGAACGGCGTGACAC

TGTCAACCAAACTGAAGGACGGTGTCAATTTCAATGTGGATGACATT

AACTTCAGCCCCGTACTGGGCTGTTTGGGTAGTGAGTGTTCTAAGGC

TAGCAGCCGCTCCGCCATTGAGGACTTGTTGTTTGATAAAGTTAAGC

TGAGTGACGTTGGATTTGTTGAGGCGTATAATAACTGTACCGGTGGT

GCAGAGATAAGGGATCTGATCTGTGTCCAGAGTTATAAGGGGATTA

AGGTTCTCCCCCCGCTACTCTCGGAGAATCAGATATCAGGATACACC

CTGGCCGCTACCTCAGCCTCGCTGTTTCCCCCTTGGACCGCTGCCGCC

GGTGTCCCATTTTATTTGAATGTGCAGTATCGGATCAACGGTCTGGG

AGTGACAATGGACGTGCTGTCTCAGAACCAGAAACTGATCGCCAAT

GCATTCAACAATGCTCTGCACGCCATCCAGCAAGGGTTTGACGCTAC

AAATTCTGCCCTCGTAAAAATCCAGGCCGTGGTGAATGCTAACGCCG

AAGCCCTTAATAATCTGCTCCAGCAGCTTTCTAACCGCTTTGGAGCT

ATTTCTGCCTCACTGCAGGAAATTCTATCCAGACTGGATCCCCCTGA

GGCAGAAGCCCAAATCGACCGTCTCATAAACGGCAGACTCACTGCT

CTTAACGCCTACGTTAGTCAACAATTGAGCGATTCGACCTTGGTGAA

ATTCAGCGCAGCTCAGGCTATGGAGAAGGTGAACGAGTGCGTGAAG

TCACAGAGCTCCAGAATCAATTTCTGTGGCAATGGGAACCATATCAT

CTCCTTGGTTCAGAATGCTCCCTACGGCCTGTATTTCATCCACTTCAA

CTACGTGCCCACGAAGTACGTTACAGCCAAAGTGTCCCCCGGACTGT

GCATCGCTGGTAACAGGGGCATTGCACCAAAATCCGGCTACTTCGTC

AATGTCAACAACACATGGATGTATACTGGGAGTGGTTATTATTACCC

TGAACCTATAACAGAGAACAATGTAGTAGTCATGTCCACATGCGCC

GTCAATTATACTAAGGCCCCCTATGTTATGCTCAACACTTCAATTCCC

AATCTCCCGGATTTCAAAGAAGAGCTGGATCAGTGGTTTAAGAATCA

GACATCCGTGGCCCCTGACTTAAGCTTGGATTATATCAATGTGACTT

TTTTAGACTTACAGGTCGAGATGAACCGACTCCAGGAAGCTATAAA

AGTACTGAACCACTCCTATATCAATCTGAAAGATATCGGTACATACG

AATATTACGTAAAATGGCCTTGGTATGTGTGGCTACTAATTTGCCTT

GCGGGCGTGGCTATGCTGGTCCTGCTGTTCTTCATTtgctgctccaatggatcgt

tacaatgcagaatttgcattTGA

PDI-OC43-H1cCT-DNA(SEQ ID NO：141)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgGTGAT

CGGCGATCTGAATTGTACCCTGGATCCCCGCCTGAAAGGGAGCTTTA

ACAACCGAGATACAGGACCCCCGTCTATATCCATAGATACAGTGGA

TGTTACGAACGGGCTCGGCACCTACTATGTGCTAGACCGAGTTTATT

TGAACACCACCTTATTCCTCAATGGATACTACCCAACTTCAGGTAGT

ACTTACAGAAACATGGCGCTGAAGGGTACGGATCTGCTGAGCACCC

TATGGTTTAAACCTCCCTTCCTCTCGGACTTTATTAATGGCATCTTCG

CTAAGGTGAAAAACACGAAGGTTTTCAAAGATGGAGTGATGTATTC

AGAGTTCCCTGCGATCACCATTGGAAGTACCTTCGTGAATACTTCCT

ATAGCGTGGTGGTTCAACCACGGACAATCAACTCCACCCAGGACGG

CGTCAACAAGCTCCAGGGATTGCTGGAGGTGTCAGTCTGTCAATATA

ACATGTGTGAGTACCCACACACTATCTGTCACCCTAATCTAGGCAAC

CACTTTAAGGAACTGTGGCACTACGATACGGGGGTGGTAAGTTGCTT

ATATAAGAGAAATTTCACCTATGATGTTAATGCAACGTACCTGTACT

TTCACTTCTATCAAGAAGGAGGAACTTTCTACGCATATTTCACAGAT

ACCGGCTTTGTGACGAAATTCTTATTCAACGTTTACCTCGGAATGGC

ATTAAGCCATTATTACGTGATGCCTCTCACTTGCATCAGACGCCCTA

AGGATGGTTTTTCTCTGGAGTACTGGGTCACTCCCCTGACACCACGG

CAGTACCTGCTTGCTTTTAACCAGGACGGTATCATTTTTAATGCCGTC

GATTGTATGAGCGATTTTATGAGCGAGATAAAGTGCAAGACCCAAT

CTATTGCTCCGCCCACGGGGGTGTACGAACTGAATGGTTACACCGTC

CAGCCCGTTGCCGATGTATATAGACGGAAACCAGACCTGCCCAATTG

CAACATCGAAGCTTGGTTAAACGATAAGTCAGTGCCCTCCCCCCTCA

ATTGGGAGAGGAAGACTTTCTCCAACTGTAATTTCAACATGTCAAGC

CTGATGTCTTTCATTCAAGCCGATTCGTTCACTTGTAATAATATAGAT

GCAGCAAAGATCTATGGTATGTGCTTCAGTTCCATCACAATAGATAA

GTTTGCAATACCAAACCGTCGCAAGGTGGACCTTCAGCTCGGCAACC

TGGGCTATCTGCAGTCCAGCAATTATAGAATAGACACCACCGCCACA

TCATGTCAGCTGTACTATAACCTCCCAGCAGCGAACGTCAGTGTTAG

TAGGTTCAATCCTTCTACCTGGAATAAAAGGTTTGGATTCATCGAAG

ATAGTGTGTTCGTACCTCAGCCAACAGGAGTGTTCACCAATCACAGC

GTGGTCTACGCCCAACATTGCTTCAAGGCACCCAAAAATTTCTGCCC

ATGTAGCAGTTGCTCCTGCCCGGGTAAGAACAATGGGATCGGCACCT

GCCCAGCAGGCACCAATTCACTTACATGCGATAATCTGTGTACACTG

GATCCTATTACACTTAAGGCCCCTGATACCTACAAATGCCCCCAGAG

CAAGAGCCTGGTCGGTATCGGAGAACACTGTTCCGGACTTGCAGTA

AAAAGCGACTATTGTGGAAATAACTCTTGCACTTGTCAGCCACAAGC

CTTCCTCGGTTGGTCCGCTGACTCTTGTTTACAAGGGGATAAGTGTA

ACATCTTCGCAAATTTCATCTTACACGATGTGAATAACGGCTTAACA

TGCAGCACAGATCTCCAGAAGGCAAACACAGAGATCGAATTAGGAG

TCTGCGTTAATTACGATCTCTACGGGATCTCTGGCCAGGGCATCTTC

GTGGAGGTTAATGCTACCTACTACAATAGTTGGCAAAATCTGCTCTA

CGATAGCAATGGCAACCTCTATGGATTCAGAGACTATATTACTAACA

GGACGTTCATGATTCACTCGTGCTATTCCGGGCGGGTGTCAGCAGCT

TATCACGCAAATTCTTCAGAGCCAGCTCTGCTATTCCGAAACATAAA

ATGTAATTACGTGTTCAATAATTCACTGACTCGGCAGCTGCAGCCGA

TTAATTACAGCTTCGACAGCTACCTTGGTTGCGTTGTTAACGCCTAC

AACTCCACTGCCATATCAGTTCAGACCTGCGACCTTACTGTGGGCTC

TGGCTATTGTGTCGATTATTCAAAGAACGGGGGGAGCGGGTCCGCA

ATAACAACTGGCTATAGGTTCACCAATTTTGAGCCTTTCACCGTGAA

TAGTGTCAACGATAGCCTGGAGCCTGTCGGAGGTCTTTATGAGATAC

AAATCCCCTCCGAGTTCACAATTGGCAACATGGAAGAGTTCATCCAG

ACGAGTTCCCCAAAGGTGACGATCGATTGCGCGGCTTTCGTCTGCGG

CGACTACGCCGCATGCAAGTTACAACTCGTTGAGTATGGAAGTTTTT

GCGATAATATAAACGCAATTCTGACTGAAGTGAACGAACTGCTGGA

CACCACTCAGTTGCAGGTGGCAAATTCGCTCATGAACGGCGTGACAC

TGTCAACCAAACTGAAGGACGGTGTCAATTTCAATGTGGATGACATT

AACTTCAGCCCCGTACTGGGCTGTTTGGGTAGTGAGTGTTCTAAGGC

TAGCAGCCGCTCCGCCATTGAGGACTTGTTGTTTGATAAAGTTAAGC

TGAGTGACGTTGGATTTGTTGAGGCGTATAATAACTGTACCGGTGGT

GCAGAGATAAGGGATCTGATCTGTGTCCAGAGTTATAAGGGGATTA

AGGTTCTCCCCCCGCTACTCTCGGAGAATCAGATATCAGGATACACC

CTGGCCGCTACCTCAGCCTCGCTGTTTCCCCCTTGGACCGCTGCCGCC

GGTGTCCCATTTTATTTGAATGTGCAGTATCGGATCAACGGTCTGGG

AGTGACAATGGACGTGCTGTCTCAGAACCAGAAACTGATCGCCAAT

GCATTCAACAATGCTCTGCACGCCATCCAGCAAGGGTTTGACGCTAC

AAATTCTGCCCTCGTAAAAATCCAGGCCGTGGTGAATGCTAACGCCG

AAGCCCTTAATAATCTGCTCCAGCAGCTTTCTAACCGCTTTGGAGCT

ATTTCTGCCTCACTGCAGGAAATTCTATCCAGACTGGATCCCCCTGA

GGCAGAAGCCCAAATCGACCGTCTCATAAACGGCAGACTCACTGCT

CTTAACGCCTACGTTAGTCAACAATTGAGCGATTCGACCTTGGTGAA

ATTCAGCGCAGCTCAGGCTATGGAGAAGGTGAACGAGTGCGTGAAG

TCACAGAGCTCCAGAATCAATTTCTGTGGCAATGGGAACCATATCAT

CTCCTTGGTTCAGAATGCTCCCTACGGCCTGTATTTCATCCACTTCAA

CTACGTGCCCACGAAGTACGTTACAGCCAAAGTGTCCCCCGGACTGT

GCATCGCTGGTAACAGGGGCATTGCACCAAAATCCGGCTACTTCGTC

AATGTCAACAACACATGGATGTATACTGGGAGTGGTTATTATTACCC

TGAACCTATAACAGAGAACAATGTAGTAGTCATGTCCACATGCGCC

GTCAATTATACTAAGGCCCCCTATGTTATGCTCAACACTTCAATTCCC

AATCTCCCGGATTTCAAAGAAGAGCTGGATCAGTGGTTTAAGAATCA

GACATCCGTGGCCCCTGACTTAAGCTTGGATTATATCAATGTGACTT

TTTTAGACTTACAGGTCGAGATGAACCGACTCCAGGAAGCTATAAA

AGTACTGAACCACTCCTATATCAATCTGAAAGATATCGGTACATACG

AATATTACGTAAAATGGCCTTGGTATGTGTGGCTACTAATTTGCCTT

GCGGGCGTGGCTATGCTGGTCCTGCTGTTCTTCATTagcttctggatgtgctcta

atgggtctctacagtgtagaatatgtattTGA

PDI-OC43-wtTMCT-AA(SEQ ID NO：142)

MAKNVAIFGLLFSLLVLVPSQIFAVIGDLNCTLDPRLKGSFNNRDTGPPS

ISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGT

DLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVN

TSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLG

NHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFT

DTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPR

QYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQP

VADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMS

FIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSS

NYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPT

GVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCD

NLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQ

PQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELG

VCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNR

TFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYS

FDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNGGSGSAITTGY

RFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDC

AAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLM

NGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDK

VKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTL

AATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAF

NNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISA

SLQEILSRLDPPEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQA

MEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVT

AKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVV

VMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLD

YINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYVWL

LICLAGVAMLVLLFFICCCTGCGTSCFKKCGGCCDDYTGYQELVIKTSH

DD

PDI-OC43-H5iTMCT-AA(SEQ ID NO：143)

MAKNVAIFGLLFSLLVLVPSQIFAVIGDLNCTLDPRLKGSFNNRDTGPPS

ISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGT

DLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVN

TSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLG

NHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFT

DTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPR

QYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQP

VADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMS

FIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSS

NYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPT

GVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCD

NLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQ

PQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELG

VCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNR

TFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYS

FDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNGGSGSAITTGY

RFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDC

AAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLM

NGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDK

VKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTL

AATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAF

NNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISA

SLQEILSRLDPPEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQA

MEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVT

AKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVV

VMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLD

YINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYQILS

IYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

PDI-OC43-H5iCT-AA(SEQ ID NO：144)

MAKNVAIFGLLFSLLVLVPSQIFAVIGDLNCTLDPRLKGSFNNRDTGPPS

ISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGT

DLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVN

TSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLG

NHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFT

DTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPR

QYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQP

VADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMS

FIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSS

NYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPT

GVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCD

NLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQ

PQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELG

VCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNR

TFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYS

FDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNGGSGSAITTGY

RFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDC

AAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLM

NGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDK

VKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTL

AATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAF

NNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISA

SLQEILSRLDPPEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQA

MEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVT

AKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVV

VMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLD

YINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYVWL

LICLAGVAMLVLLFFISLWMCSNGSLQCRICI

PDI-OC43-H5iCT(V4)-AA(SEQ ID NO：145)

MAKNVAIFGLLFSLLVLVPSQIFAVIGDLNCTLDPRLKGSFNNRDTGPPS

ISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGT

DLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVN

TSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLG

NHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFT

DTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPR

QYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQP

VADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMS

FIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSS

NYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPT

GVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCD

NLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQ

PQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELG

VCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNR

TFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYS

FDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNGGSGSAITTGY

RFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDC

AAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLM

NGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDK

VKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTL

AATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAF

NNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISA

SLQEILSRLDPPEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQA

MEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVT

AKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVV

VMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLD

YINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYVWL

LICLAGVAMLVLLFFICCSNGSLQCRICI

PDI-OC43-H1cCT-AA(SEQ ID NO：146)

MAKNVAIFGLLFSLLVLVPSQIFAVIGDLNCTLDPRLKGSFNNRDTGPPS

ISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGT

DLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVN

TSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLG

NHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFT

DTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPR

QYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQP

VADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMS

FIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSS

NYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPT

GVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCD

NLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQ

PQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELG

VCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNR

TFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYS

FDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNGGSGSAITTGY

RFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDC

AAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLM

NGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDK

VKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTL

AATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAF

NNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISA

SLQEILSRLDPPEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQA

MEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVT

AKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVV

VMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLD

YINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYVWL

LICLAGVAMLVLLFFISFWMCSNGSLQCRICI

IF(CoV229EwtCT).r(SEQ ID NO：147)

ACGACACGACTAAGGCCTTCACTGTATGTGGATCTTTTCGACATCGT

A

PDI-229E-wtTMCT-DNA(SEQ ID NO：148)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgCAAAC

GACTAATGGGCTGAACACCAGTTACAGCGTCTGTAACGGCTGCGTCG

GATATAGCGAGAACGTGTTCGCAGTGGAAAGTGGGGGGTACATTCC

TTCCGACTTCGCTTTCAATAACTGGTTTCTCCTGACTAACACAAGCTC

CGTCGTGGATGGCGTGGTCAGGTCCTTTCAGCCTCTTCTCCTGAATTG

CCTGTGGTCTGTGTCCGGGTTAAGATTCACTACAGGCTTCGTATACTT

CAACGGGACGGGCCGGGGGGATTGCAAGGGCTTCTCCTCCGACGTG

CTGTCAGATGTGATCCGTTACAATCTGAACTTCGAAGAGAACTTACG

GCGGGGGACAATCCTGTTCAAAACATCATATGGCGTAGTCGTATTTT

ACTGCACCAATAATACCCTGGTGAGTGGGGACGCCCATATTCCCTTC

GGAACAGTGCTGGGTAACTTTTACTGTTTTGTCAACACTACGATCGG

AAACGAAACCACTAGCGCCTTTGTCGGAGCTCTGCCAAAAACAGTT

AGGGAGTTCGTGATCTCTCGGACCGGTCACTTCTATATCAACGGCTA

CCGTTATTTTACTTTGGGCAACGTCGAAGCCGTCAATTTTAATGTGA

CAACTGCAGAGACAACTGACTTTTGCACTGTGGCTCTCGCCAGTTAT

GCCGATGTGCTGGTGAATGTAAGTCAAACGTCAATTGCCAACATCAT

CTATTGTAACTCAGTAATCAACCGGCTCCGCTGTGACCAACTCTCAT

TCGACGTCCCCGACGGATTCTATTCCACGAGCCCGATTCAGAGCGTG

GAACTGCCAGTTTCCATCGTATCCCTCCCAGTTTACCACAAGCACAC

TTTTATCGTTCTCTACGTAGATTTTAAACCCCAGTCAGGAGGAGGGA

AATGCTTCAACTGCTACCCGGCTGGCGTGAACATCACCTTGGCCAAT

TTTAATGAAACTAAAGGGCCCCTTTGCGTGGATACGTCACACTTTAC

CACAAAGTATGTTGCAGTCTATGCTAACGTCGGCAGGTGGTCAGCGT

CCATTAACACAGGCAATTGCCCGTTCTCTTTCGGGAAAGTGAACAAC

TTCGTGAAGTTTGGAAGTGTGTGCTTCAGTTTGAAAGACATTCCGGG

CGGCTGCGCCATGCCTATTGTGGCTAATTGGGCTTATTCCAAGTACT

ACACCATTGGCTCTCTCTACGTTAGCTGGAGCGACGGTGACGGTATA

ACGGGCGTACCACAACCGGTGGAAGGGGTCAGCTCTTTCATGAATG

TCACTCTGGACAAGTGTACCAAATATAATATATACGATGTGAGTGGA

GTGGGCGTTATACGCGTGTCTAACGACACCTTTCTAAACGGCATAAC

CTACACAAGCACGTCAGGCAATCTGTTAGGTTTTAAAGACGTCACTA

AAGGCACTATATATAGCATCACCCCATGCAACCCACCTGATCAATTA

GTCGTATATCAGCAAGCTGTTGTGGGTGCTATGCTGTCAGAAAACTT

CACCAGCTACGGGTTCTCCAATGTGGTGGAACTGCCCAAATTCTTTT

ACGCTAGCAATGGCACATATAACTGTACTGACGCCGTCTTGACTTAC

AGTTCATTCGGAGTGTGCGCGGACGGCAGCATTATCGCCGTGCAGCC

GGCCAATGTCAGCTATGATTCCGTTTCCGCCATCGTGACAGCCAACT

TGTCGATTCCCTCTAACTGGACAACGTCTGTCCAAGTCGAATATCTG

CAGATCACCTCAACCCCCATAGTAGTCGATTGCTCAACCTACGTCTG

CAACGGTAATGTCAGATGTGTCGAGCTGCTCAAGCAGTACACCTCCG

CCTGTAAGACTATTGAGGATGCATTAAGAAATAGTGCAAGATTGGA

AAGCGCCGATGTGTCGGAAATGCTAACCTTCGATAAGAAGGCATTC

ACACTGGCGAACGTAAGCTCTTTCGGCGATTACAACCTGTCTTCGGT

AATCCCTAGCTTGCCCACATCCGGCTCTCGGGTGGCGGGGCGGAGCG

CTATCGAGGACATTTTATTCTCGAAACTGGTTACATCTGGGCTCGGA

ACTGTGGACGCCGATTACAAGAAGTGCACCAAGGGCCTAAGCATCG

CCGACCTCGCCTGTGCTCAGTACTACAACGGAATTATGGTGCTGCCA

GGTGTCGCTGACGCAGAGCGGATGGCTATGTATACCGGCAGTCTCAT

TGGCGGGATTGCGTTGGGCGGCCTGACGTCCGCTGTCTCCATCCCTT

TCTCTCTGGCTATACAAGCCCGACTGAATTATGTGGCCCTGCAGACT

GATGTCCTGCAAGAAAATCAGAAGATTCTTGCCGCCAGCTTCAACAA

GGCCATGACTAATATTGTGGATGCGTTTACCGGAGTGAATGACGCCA

TCACCCAAACGTCCCAAGCCCTGCAGACAGTCGCCACGGCGTTAAA

CAAAATCCAGGATGTAGTGAATCAGCAAGGGAACAGCTTGAATCAC

CTGACGTCCCAGTTAAGACAGAACTTTCAGGCAATCAGTAGCTCAAT

CCAGGCTATCTACGATCGATTAGATCCTCCTCAGGCAGATCAGCAGG

TGGATCGGCTCATCACCGGCCGCCTCGCGGCATTGAATGTTTTCGTA

AGTCATACCTTGACCAAGTACACGGAGGTGAGGGCCAGTCGCCAGC

TGGCTCAGCAAAAAGTGAATGAGTGTGTGAAATCACAGAGCAAACG

GTACGGGTTTTGTGGAAATGGGACGCACATCTTTAGCATCGTTAATG

CTGCCCCCGAAGGGTTAGTCTTCCTGCACACTGTGCTCCTTCCTACCC

AGTATAAAGATGTCGAAGCATGGTCTGGGCTCTGTGTCGATGGAACT

AACGGTTATGTCCTTCGACAGCCAAACCTCGCTCTCTATAAAGAAGG

GAATTACTATAGGATCACCTCAAGAATCATGTTCGAGCCCAGGATAC

CAACAATGGCCGATTTTGTGCAGATTGAAAATTGTAACGTGACCTTT

GTGAATATCAGTCGATCCGAGCTTCAAACGATTGTTCCTGAGTACAT

CGACGTGAATAAAACTCTACAAGAGCTGTCCTATAAACTGCCTAATT

ATACCGTGCCTGACCTTGTAGTCGAGCAATACAACCAGACTATTCTG

AACCTGACATCGGAAATCTCTACATTGGAGAATAAAAGCGCCGAGC

TCAATTACACAGTGCAGAAGCTGCAGACCCTGATCGACAATATTAAC

AGCACTCTTGTGGACTTAAAGTGGCTGAACCGTGTGGAGACTTACAT

CAAGTGGCCCTGGTGGGTGTGGCTCTGTATTTCCGTGGTCCTTATATT

TGTTGTAAGTATGCTGCTCCTGTGCTGTTGCTCAACCGGGTGCTGCG

GTTTTTTCTCCTGTTTCGCCTCATCCATCCGTGGCTGTTGTGAGAGCA

CTAAACTGCCATATTACGATGTCGAAAAGATCCACATACAGTGA

PDI-229E-H5iTMCT-DNA(SEQ ID NO：149)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgCAAAC

GACTAATGGGCTGAACACCAGTTACAGCGTCTGTAACGGCTGCGTCG

GATATAGCGAGAACGTGTTCGCAGTGGAAAGTGGGGGGTACATTCC

TTCCGACTTCGCTTTCAATAACTGGTTTCTCCTGACTAACACAAGCTC

CGTCGTGGATGGCGTGGTCAGGTCCTTTCAGCCTCTTCTCCTGAATTG

CCTGTGGTCTGTGTCCGGGTTAAGATTCACTACAGGCTTCGTATACTT

CAACGGGACGGGCCGGGGGGATTGCAAGGGCTTCTCCTCCGACGTG

CTGTCAGATGTGATCCGTTACAATCTGAACTTCGAAGAGAACTTACG

GCGGGGGACAATCCTGTTCAAAACATCATATGGCGTAGTCGTATTTT

ACTGCACCAATAATACCCTGGTGAGTGGGGACGCCCATATTCCCTTC

GGAACAGTGCTGGGTAACTTTTACTGTTTTGTCAACACTACGATCGG

AAACGAAACCACTAGCGCCTTTGTCGGAGCTCTGCCAAAAACAGTT

AGGGAGTTCGTGATCTCTCGGACCGGTCACTTCTATATCAACGGCTA

CCGTTATTTTACTTTGGGCAACGTCGAAGCCGTCAATTTTAATGTGA

CAACTGCAGAGACAACTGACTTTTGCACTGTGGCTCTCGCCAGTTAT

GCCGATGTGCTGGTGAATGTAAGTCAAACGTCAATTGCCAACATCAT

CTATTGTAACTCAGTAATCAACCGGCTCCGCTGTGACCAACTCTCAT

TCGACGTCCCCGACGGATTCTATTCCACGAGCCCGATTCAGAGCGTG

GAACTGCCAGTTTCCATCGTATCCCTCCCAGTTTACCACAAGCACAC

TTTTATCGTTCTCTACGTAGATTTTAAACCCCAGTCAGGAGGAGGGA

AATGCTTCAACTGCTACCCGGCTGGCGTGAACATCACCTTGGCCAAT

TTTAATGAAACTAAAGGGCCCCTTTGCGTGGATACGTCACACTTTAC

CACAAAGTATGTTGCAGTCTATGCTAACGTCGGCAGGTGGTCAGCGT

CCATTAACACAGGCAATTGCCCGTTCTCTTTCGGGAAAGTGAACAAC

TTCGTGAAGTTTGGAAGTGTGTGCTTCAGTTTGAAAGACATTCCGGG

CGGCTGCGCCATGCCTATTGTGGCTAATTGGGCTTATTCCAAGTACT

ACACCATTGGCTCTCTCTACGTTAGCTGGAGCGACGGTGACGGTATA

ACGGGCGTACCACAACCGGTGGAAGGGGTCAGCTCTTTCATGAATG

TCACTCTGGACAAGTGTACCAAATATAATATATACGATGTGAGTGGA

GTGGGCGTTATACGCGTGTCTAACGACACCTTTCTAAACGGCATAAC

CTACACAAGCACGTCAGGCAATCTGTTAGGTTTTAAAGACGTCACTA

AAGGCACTATATATAGCATCACCCCATGCAACCCACCTGATCAATTA

GTCGTATATCAGCAAGCTGTTGTGGGTGCTATGCTGTCAGAAAACTT

CACCAGCTACGGGTTCTCCAATGTGGTGGAACTGCCCAAATTCTTTT

ACGCTAGCAATGGCACATATAACTGTACTGACGCCGTCTTGACTTAC

AGTTCATTCGGAGTGTGCGCGGACGGCAGCATTATCGCCGTGCAGCC

GGCCAATGTCAGCTATGATTCCGTTTCCGCCATCGTGACAGCCAACT

TGTCGATTCCCTCTAACTGGACAACGTCTGTCCAAGTCGAATATCTG

CAGATCACCTCAACCCCCATAGTAGTCGATTGCTCAACCTACGTCTG

CAACGGTAATGTCAGATGTGTCGAGCTGCTCAAGCAGTACACCTCCG

CCTGTAAGACTATTGAGGATGCATTAAGAAATAGTGCAAGATTGGA

AAGCGCCGATGTGTCGGAAATGCTAACCTTCGATAAGAAGGCATTC

ACACTGGCGAACGTAAGCTCTTTCGGCGATTACAACCTGTCTTCGGT

AATCCCTAGCTTGCCCACATCCGGCTCTCGGGTGGCGGGGCGGAGCG

CTATCGAGGACATTTTATTCTCGAAACTGGTTACATCTGGGCTCGGA

ACTGTGGACGCCGATTACAAGAAGTGCACCAAGGGCCTAAGCATCG

CCGACCTCGCCTGTGCTCAGTACTACAACGGAATTATGGTGCTGCCA

GGTGTCGCTGACGCAGAGCGGATGGCTATGTATACCGGCAGTCTCAT

TGGCGGGATTGCGTTGGGCGGCCTGACGTCCGCTGTCTCCATCCCTT

TCTCTCTGGCTATACAAGCCCGACTGAATTATGTGGCCCTGCAGACT

GATGTCCTGCAAGAAAATCAGAAGATTCTTGCCGCCAGCTTCAACAA

GGCCATGACTAATATTGTGGATGCGTTTACCGGAGTGAATGACGCCA

TCACCCAAACGTCCCAAGCCCTGCAGACAGTCGCCACGGCGTTAAA

CAAAATCCAGGATGTAGTGAATCAGCAAGGGAACAGCTTGAATCAC

CTGACGTCCCAGTTAAGACAGAACTTTCAGGCAATCAGTAGCTCAAT

CCAGGCTATCTACGATCGATTAGATCCTCCTCAGGCAGATCAGCAGG

TGGATCGGCTCATCACCGGCCGCCTCGCGGCATTGAATGTTTTCGTA

AGTCATACCTTGACCAAGTACACGGAGGTGAGGGCCAGTCGCCAGC

TGGCTCAGCAAAAAGTGAATGAGTGTGTGAAATCACAGAGCAAACG

GTACGGGTTTTGTGGAAATGGGACGCACATCTTTAGCATCGTTAATG

CTGCCCCCGAAGGGTTAGTCTTCCTGCACACTGTGCTCCTTCCTACCC

AGTATAAAGATGTCGAAGCATGGTCTGGGCTCTGTGTCGATGGAACT

AACGGTTATGTCCTTCGACAGCCAAACCTCGCTCTCTATAAAGAAGG

GAATTACTATAGGATCACCTCAAGAATCATGTTCGAGCCCAGGATAC

CAACAATGGCCGATTTTGTGCAGATTGAAAATTGTAACGTGACCTTT

GTGAATATCAGTCGATCCGAGCTTCAAACGATTGTTCCTGAGTACAT

CGACGTGAATAAAACTCTACAAGAGCTGTCCTATAAACTGCCTAATT

ATACCGTGCCTGACCTTGTAGTCGAGCAATACAACCAGACTATTCTG

AACCTGACATCGGAAATCTCTACATTGGAGAATAAAAGCGCCGAGC

TCAATTACACAGTGCAGAAGCTGCAGACCCTGATCGACAATATTAAC

AGCACTCTTGTGGACTTAAAGTGGCTGAACCGTGTGGAGACTTACAT

CAAGTGGCCCTGGTGGcaaatactgtcaatttattcaacagtggcgagttccctagcactggcaat

catgatggctggtctatctttatggatgtgctccaatggatcgttacaatgcagaatttgcattTGA

PDI-229E-H5iCT-DNA(SEQ ID NO：150)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgCAAAC

GACTAATGGGCTGAACACCAGTTACAGCGTCTGTAACGGCTGCGTCG

GATATAGCGAGAACGTGTTCGCAGTGGAAAGTGGGGGGTACATTCC

TTCCGACTTCGCTTTCAATAACTGGTTTCTCCTGACTAACACAAGCTC

CGTCGTGGATGGCGTGGTCAGGTCCTTTCAGCCTCTTCTCCTGAATTG

CCTGTGGTCTGTGTCCGGGTTAAGATTCACTACAGGCTTCGTATACTT

CAACGGGACGGGCCGGGGGGATTGCAAGGGCTTCTCCTCCGACGTG

CTGTCAGATGTGATCCGTTACAATCTGAACTTCGAAGAGAACTTACG

GCGGGGGACAATCCTGTTCAAAACATCATATGGCGTAGTCGTATTTT

ACTGCACCAATAATACCCTGGTGAGTGGGGACGCCCATATTCCCTTC

GGAACAGTGCTGGGTAACTTTTACTGTTTTGTCAACACTACGATCGG

AAACGAAACCACTAGCGCCTTTGTCGGAGCTCTGCCAAAAACAGTT

AGGGAGTTCGTGATCTCTCGGACCGGTCACTTCTATATCAACGGCTA

CCGTTATTTTACTTTGGGCAACGTCGAAGCCGTCAATTTTAATGTGA

CAACTGCAGAGACAACTGACTTTTGCACTGTGGCTCTCGCCAGTTAT

GCCGATGTGCTGGTGAATGTAAGTCAAACGTCAATTGCCAACATCAT

CTATTGTAACTCAGTAATCAACCGGCTCCGCTGTGACCAACTCTCAT

TCGACGTCCCCGACGGATTCTATTCCACGAGCCCGATTCAGAGCGTG

GAACTGCCAGTTTCCATCGTATCCCTCCCAGTTTACCACAAGCACAC

TTTTATCGTTCTCTACGTAGATTTTAAACCCCAGTCAGGAGGAGGGA

AATGCTTCAACTGCTACCCGGCTGGCGTGAACATCACCTTGGCCAAT

TTTAATGAAACTAAAGGGCCCCTTTGCGTGGATACGTCACACTTTAC

CACAAAGTATGTTGCAGTCTATGCTAACGTCGGCAGGTGGTCAGCGT

CCATTAACACAGGCAATTGCCCGTTCTCTTTCGGGAAAGTGAACAAC

TTCGTGAAGTTTGGAAGTGTGTGCTTCAGTTTGAAAGACATTCCGGG

CGGCTGCGCCATGCCTATTGTGGCTAATTGGGCTTATTCCAAGTACT

ACACCATTGGCTCTCTCTACGTTAGCTGGAGCGACGGTGACGGTATA

ACGGGCGTACCACAACCGGTGGAAGGGGTCAGCTCTTTCATGAATG

TCACTCTGGACAAGTGTACCAAATATAATATATACGATGTGAGTGGA

GTGGGCGTTATACGCGTGTCTAACGACACCTTTCTAAACGGCATAAC

CTACACAAGCACGTCAGGCAATCTGTTAGGTTTTAAAGACGTCACTA

AAGGCACTATATATAGCATCACCCCATGCAACCCACCTGATCAATTA

GTCGTATATCAGCAAGCTGTTGTGGGTGCTATGCTGTCAGAAAACTT

CACCAGCTACGGGTTCTCCAATGTGGTGGAACTGCCCAAATTCTTTT

ACGCTAGCAATGGCACATATAACTGTACTGACGCCGTCTTGACTTAC

AGTTCATTCGGAGTGTGCGCGGACGGCAGCATTATCGCCGTGCAGCC

GGCCAATGTCAGCTATGATTCCGTTTCCGCCATCGTGACAGCCAACT

TGTCGATTCCCTCTAACTGGACAACGTCTGTCCAAGTCGAATATCTG

CAGATCACCTCAACCCCCATAGTAGTCGATTGCTCAACCTACGTCTG

CAACGGTAATGTCAGATGTGTCGAGCTGCTCAAGCAGTACACCTCCG

CCTGTAAGACTATTGAGGATGCATTAAGAAATAGTGCAAGATTGGA

AAGCGCCGATGTGTCGGAAATGCTAACCTTCGATAAGAAGGCATTC

ACACTGGCGAACGTAAGCTCTTTCGGCGATTACAACCTGTCTTCGGT

AATCCCTAGCTTGCCCACATCCGGCTCTCGGGTGGCGGGGCGGAGCG

CTATCGAGGACATTTTATTCTCGAAACTGGTTACATCTGGGCTCGGA

ACTGTGGACGCCGATTACAAGAAGTGCACCAAGGGCCTAAGCATCG

CCGACCTCGCCTGTGCTCAGTACTACAACGGAATTATGGTGCTGCCA

GGTGTCGCTGACGCAGAGCGGATGGCTATGTATACCGGCAGTCTCAT

TGGCGGGATTGCGTTGGGCGGCCTGACGTCCGCTGTCTCCATCCCTT

TCTCTCTGGCTATACAAGCCCGACTGAATTATGTGGCCCTGCAGACT

GATGTCCTGCAAGAAAATCAGAAGATTCTTGCCGCCAGCTTCAACAA

GGCCATGACTAATATTGTGGATGCGTTTACCGGAGTGAATGACGCCA

TCACCCAAACGTCCCAAGCCCTGCAGACAGTCGCCACGGCGTTAAA

CAAAATCCAGGATGTAGTGAATCAGCAAGGGAACAGCTTGAATCAC

CTGACGTCCCAGTTAAGACAGAACTTTCAGGCAATCAGTAGCTCAAT

CCAGGCTATCTACGATCGATTAGATCCTCCTCAGGCAGATCAGCAGG

TGGATCGGCTCATCACCGGCCGCCTCGCGGCATTGAATGTTTTCGTA

AGTCATACCTTGACCAAGTACACGGAGGTGAGGGCCAGTCGCCAGC

TGGCTCAGCAAAAAGTGAATGAGTGTGTGAAATCACAGAGCAAACG

GTACGGGTTTTGTGGAAATGGGACGCACATCTTTAGCATCGTTAATG

CTGCCCCCGAAGGGTTAGTCTTCCTGCACACTGTGCTCCTTCCTACCC

AGTATAAAGATGTCGAAGCATGGTCTGGGCTCTGTGTCGATGGAACT

AACGGTTATGTCCTTCGACAGCCAAACCTCGCTCTCTATAAAGAAGG

GAATTACTATAGGATCACCTCAAGAATCATGTTCGAGCCCAGGATAC

CAACAATGGCCGATTTTGTGCAGATTGAAAATTGTAACGTGACCTTT

GTGAATATCAGTCGATCCGAGCTTCAAACGATTGTTCCTGAGTACAT

CGACGTGAATAAAACTCTACAAGAGCTGTCCTATAAACTGCCTAATT

ATACCGTGCCTGACCTTGTAGTCGAGCAATACAACCAGACTATTCTG

AACCTGACATCGGAAATCTCTACATTGGAGAATAAAAGCGCCGAGC

TCAATTACACAGTGCAGAAGCTGCAGACCCTGATCGACAATATTAAC

AGCACTCTTGTGGACTTAAAGTGGCTGAACCGTGTGGAGACTTACAT

CAAGTGGCCCTGGTGGGTGTGGCTCTGTATTTCCGTGGTCCTTATATT

TGTTGTAAGTATGCTGCTCCTGtctttatggatgtgctccaatggatcgttacaatgcagaattt

gcattTGA

PDI-229E-H5iCT(V4)-DNA(SEQ ID NO：151)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgCAAAC

GACTAATGGGCTGAACACCAGTTACAGCGTCTGTAACGGCTGCGTCG

GATATAGCGAGAACGTGTTCGCAGTGGAAAGTGGGGGGTACATTCC

TTCCGACTTCGCTTTCAATAACTGGTTTCTCCTGACTAACACAAGCTC

CGTCGTGGATGGCGTGGTCAGGTCCTTTCAGCCTCTTCTCCTGAATTG

CCTGTGGTCTGTGTCCGGGTTAAGATTCACTACAGGCTTCGTATACTT

CAACGGGACGGGCCGGGGGGATTGCAAGGGCTTCTCCTCCGACGTG

CTGTCAGATGTGATCCGTTACAATCTGAACTTCGAAGAGAACTTACG

GCGGGGGACAATCCTGTTCAAAACATCATATGGCGTAGTCGTATTTT

ACTGCACCAATAATACCCTGGTGAGTGGGGACGCCCATATTCCCTTC

GGAACAGTGCTGGGTAACTTTTACTGTTTTGTCAACACTACGATCGG

AAACGAAACCACTAGCGCCTTTGTCGGAGCTCTGCCAAAAACAGTT

AGGGAGTTCGTGATCTCTCGGACCGGTCACTTCTATATCAACGGCTA

CCGTTATTTTACTTTGGGCAACGTCGAAGCCGTCAATTTTAATGTGA

CAACTGCAGAGACAACTGACTTTTGCACTGTGGCTCTCGCCAGTTAT

GCCGATGTGCTGGTGAATGTAAGTCAAACGTCAATTGCCAACATCAT

CTATTGTAACTCAGTAATCAACCGGCTCCGCTGTGACCAACTCTCAT

TCGACGTCCCCGACGGATTCTATTCCACGAGCCCGATTCAGAGCGTG

GAACTGCCAGTTTCCATCGTATCCCTCCCAGTTTACCACAAGCACAC

TTTTATCGTTCTCTACGTAGATTTTAAACCCCAGTCAGGAGGAGGGA

AATGCTTCAACTGCTACCCGGCTGGCGTGAACATCACCTTGGCCAAT

TTTAATGAAACTAAAGGGCCCCTTTGCGTGGATACGTCACACTTTAC

CACAAAGTATGTTGCAGTCTATGCTAACGTCGGCAGGTGGTCAGCGT

CCATTAACACAGGCAATTGCCCGTTCTCTTTCGGGAAAGTGAACAAC

TTCGTGAAGTTTGGAAGTGTGTGCTTCAGTTTGAAAGACATTCCGGG

CGGCTGCGCCATGCCTATTGTGGCTAATTGGGCTTATTCCAAGTACT

ACACCATTGGCTCTCTCTACGTTAGCTGGAGCGACGGTGACGGTATA

ACGGGCGTACCACAACCGGTGGAAGGGGTCAGCTCTTTCATGAATG

TCACTCTGGACAAGTGTACCAAATATAATATATACGATGTGAGTGGA

GTGGGCGTTATACGCGTGTCTAACGACACCTTTCTAAACGGCATAAC

CTACACAAGCACGTCAGGCAATCTGTTAGGTTTTAAAGACGTCACTA

AAGGCACTATATATAGCATCACCCCATGCAACCCACCTGATCAATTA

GTCGTATATCAGCAAGCTGTTGTGGGTGCTATGCTGTCAGAAAACTT

CACCAGCTACGGGTTCTCCAATGTGGTGGAACTGCCCAAATTCTTTT

ACGCTAGCAATGGCACATATAACTGTACTGACGCCGTCTTGACTTAC

AGTTCATTCGGAGTGTGCGCGGACGGCAGCATTATCGCCGTGCAGCC

GGCCAATGTCAGCTATGATTCCGTTTCCGCCATCGTGACAGCCAACT

TGTCGATTCCCTCTAACTGGACAACGTCTGTCCAAGTCGAATATCTG

CAGATCACCTCAACCCCCATAGTAGTCGATTGCTCAACCTACGTCTG

CAACGGTAATGTCAGATGTGTCGAGCTGCTCAAGCAGTACACCTCCG

CCTGTAAGACTATTGAGGATGCATTAAGAAATAGTGCAAGATTGGA

AAGCGCCGATGTGTCGGAAATGCTAACCTTCGATAAGAAGGCATTC

ACACTGGCGAACGTAAGCTCTTTCGGCGATTACAACCTGTCTTCGGT

AATCCCTAGCTTGCCCACATCCGGCTCTCGGGTGGCGGGGCGGAGCG

CTATCGAGGACATTTTATTCTCGAAACTGGTTACATCTGGGCTCGGA

ACTGTGGACGCCGATTACAAGAAGTGCACCAAGGGCCTAAGCATCG

CCGACCTCGCCTGTGCTCAGTACTACAACGGAATTATGGTGCTGCCA

GGTGTCGCTGACGCAGAGCGGATGGCTATGTATACCGGCAGTCTCAT

TGGCGGGATTGCGTTGGGCGGCCTGACGTCCGCTGTCTCCATCCCTT

TCTCTCTGGCTATACAAGCCCGACTGAATTATGTGGCCCTGCAGACT

GATGTCCTGCAAGAAAATCAGAAGATTCTTGCCGCCAGCTTCAACAA

GGCCATGACTAATATTGTGGATGCGTTTACCGGAGTGAATGACGCCA

TCACCCAAACGTCCCAAGCCCTGCAGACAGTCGCCACGGCGTTAAA

CAAAATCCAGGATGTAGTGAATCAGCAAGGGAACAGCTTGAATCAC

CTGACGTCCCAGTTAAGACAGAACTTTCAGGCAATCAGTAGCTCAAT

CCAGGCTATCTACGATCGATTAGATCCTCCTCAGGCAGATCAGCAGG

TGGATCGGCTCATCACCGGCCGCCTCGCGGCATTGAATGTTTTCGTA

AGTCATACCTTGACCAAGTACACGGAGGTGAGGGCCAGTCGCCAGC

TGGCTCAGCAAAAAGTGAATGAGTGTGTGAAATCACAGAGCAAACG

GTACGGGTTTTGTGGAAATGGGACGCACATCTTTAGCATCGTTAATG

CTGCCCCCGAAGGGTTAGTCTTCCTGCACACTGTGCTCCTTCCTACCC

AGTATAAAGATGTCGAAGCATGGTCTGGGCTCTGTGTCGATGGAACT

AACGGTTATGTCCTTCGACAGCCAAACCTCGCTCTCTATAAAGAAGG

GAATTACTATAGGATCACCTCAAGAATCATGTTCGAGCCCAGGATAC

CAACAATGGCCGATTTTGTGCAGATTGAAAATTGTAACGTGACCTTT

GTGAATATCAGTCGATCCGAGCTTCAAACGATTGTTCCTGAGTACAT

CGACGTGAATAAAACTCTACAAGAGCTGTCCTATAAACTGCCTAATT

ATACCGTGCCTGACCTTGTAGTCGAGCAATACAACCAGACTATTCTG

AACCTGACATCGGAAATCTCTACATTGGAGAATAAAAGCGCCGAGC

TCAATTACACAGTGCAGAAGCTGCAGACCCTGATCGACAATATTAAC

AGCACTCTTGTGGACTTAAAGTGGCTGAACCGTGTGGAGACTTACAT

CAAGTGGCCCTGGTGGGTGTGGCTCTGTATTTCCGTGGTCCTTATATT

TGTTGTAAGTATGCTGCTCCTGtgctgctccaatggatcgttacaatgcagaatttgcattTG

A

PDI-229E-H1cCT-DNA(SEQ ID NO：152)

atggcgaaaaacgttgcgattttcggcttattgttttctcttcttgtgttggttccttctcagatcttcgcgCAAAC

GACTAATGGGCTGAACACCAGTTACAGCGTCTGTAACGGCTGCGTCG

GATATAGCGAGAACGTGTTCGCAGTGGAAAGTGGGGGGTACATTCC

TTCCGACTTCGCTTTCAATAACTGGTTTCTCCTGACTAACACAAGCTC

CGTCGTGGATGGCGTGGTCAGGTCCTTTCAGCCTCTTCTCCTGAATTG

CCTGTGGTCTGTGTCCGGGTTAAGATTCACTACAGGCTTCGTATACTT

CAACGGGACGGGCCGGGGGGATTGCAAGGGCTTCTCCTCCGACGTG

CTGTCAGATGTGATCCGTTACAATCTGAACTTCGAAGAGAACTTACG

GCGGGGGACAATCCTGTTCAAAACATCATATGGCGTAGTCGTATTTT

ACTGCACCAATAATACCCTGGTGAGTGGGGACGCCCATATTCCCTTC

GGAACAGTGCTGGGTAACTTTTACTGTTTTGTCAACACTACGATCGG

AAACGAAACCACTAGCGCCTTTGTCGGAGCTCTGCCAAAAACAGTT

AGGGAGTTCGTGATCTCTCGGACCGGTCACTTCTATATCAACGGCTA

CCGTTATTTTACTTTGGGCAACGTCGAAGCCGTCAATTTTAATGTGA

CAACTGCAGAGACAACTGACTTTTGCACTGTGGCTCTCGCCAGTTAT

GCCGATGTGCTGGTGAATGTAAGTCAAACGTCAATTGCCAACATCAT

CTATTGTAACTCAGTAATCAACCGGCTCCGCTGTGACCAACTCTCAT

TCGACGTCCCCGACGGATTCTATTCCACGAGCCCGATTCAGAGCGTG

GAACTGCCAGTTTCCATCGTATCCCTCCCAGTTTACCACAAGCACAC

TTTTATCGTTCTCTACGTAGATTTTAAACCCCAGTCAGGAGGAGGGA

AATGCTTCAACTGCTACCCGGCTGGCGTGAACATCACCTTGGCCAAT

TTTAATGAAACTAAAGGGCCCCTTTGCGTGGATACGTCACACTTTAC

CACAAAGTATGTTGCAGTCTATGCTAACGTCGGCAGGTGGTCAGCGT

CCATTAACACAGGCAATTGCCCGTTCTCTTTCGGGAAAGTGAACAAC

TTCGTGAAGTTTGGAAGTGTGTGCTTCAGTTTGAAAGACATTCCGGG

CGGCTGCGCCATGCCTATTGTGGCTAATTGGGCTTATTCCAAGTACT

ACACCATTGGCTCTCTCTACGTTAGCTGGAGCGACGGTGACGGTATA

ACGGGCGTACCACAACCGGTGGAAGGGGTCAGCTCTTTCATGAATG

TCACTCTGGACAAGTGTACCAAATATAATATATACGATGTGAGTGGA

GTGGGCGTTATACGCGTGTCTAACGACACCTTTCTAAACGGCATAAC

CTACACAAGCACGTCAGGCAATCTGTTAGGTTTTAAAGACGTCACTA

AAGGCACTATATATAGCATCACCCCATGCAACCCACCTGATCAATTA

GTCGTATATCAGCAAGCTGTTGTGGGTGCTATGCTGTCAGAAAACTT

CACCAGCTACGGGTTCTCCAATGTGGTGGAACTGCCCAAATTCTTTT

ACGCTAGCAATGGCACATATAACTGTACTGACGCCGTCTTGACTTAC

AGTTCATTCGGAGTGTGCGCGGACGGCAGCATTATCGCCGTGCAGCC

GGCCAATGTCAGCTATGATTCCGTTTCCGCCATCGTGACAGCCAACT

TGTCGATTCCCTCTAACTGGACAACGTCTGTCCAAGTCGAATATCTG

CAGATCACCTCAACCCCCATAGTAGTCGATTGCTCAACCTACGTCTG

CAACGGTAATGTCAGATGTGTCGAGCTGCTCAAGCAGTACACCTCCG

CCTGTAAGACTATTGAGGATGCATTAAGAAATAGTGCAAGATTGGA

AAGCGCCGATGTGTCGGAAATGCTAACCTTCGATAAGAAGGCATTC

ACACTGGCGAACGTAAGCTCTTTCGGCGATTACAACCTGTCTTCGGT

AATCCCTAGCTTGCCCACATCCGGCTCTCGGGTGGCGGGGCGGAGCG

CTATCGAGGACATTTTATTCTCGAAACTGGTTACATCTGGGCTCGGA

ACTGTGGACGCCGATTACAAGAAGTGCACCAAGGGCCTAAGCATCG

CCGACCTCGCCTGTGCTCAGTACTACAACGGAATTATGGTGCTGCCA

GGTGTCGCTGACGCAGAGCGGATGGCTATGTATACCGGCAGTCTCAT

TGGCGGGATTGCGTTGGGCGGCCTGACGTCCGCTGTCTCCATCCCTT

TCTCTCTGGCTATACAAGCCCGACTGAATTATGTGGCCCTGCAGACT

GATGTCCTGCAAGAAAATCAGAAGATTCTTGCCGCCAGCTTCAACAA

GGCCATGACTAATATTGTGGATGCGTTTACCGGAGTGAATGACGCCA

TCACCCAAACGTCCCAAGCCCTGCAGACAGTCGCCACGGCGTTAAA

CAAAATCCAGGATGTAGTGAATCAGCAAGGGAACAGCTTGAATCAC

CTGACGTCCCAGTTAAGACAGAACTTTCAGGCAATCAGTAGCTCAAT

CCAGGCTATCTACGATCGATTAGATCCTCCTCAGGCAGATCAGCAGG

TGGATCGGCTCATCACCGGCCGCCTCGCGGCATTGAATGTTTTCGTA

AGTCATACCTTGACCAAGTACACGGAGGTGAGGGCCAGTCGCCAGC

TGGCTCAGCAAAAAGTGAATGAGTGTGTGAAATCACAGAGCAAACG

GTACGGGTTTTGTGGAAATGGGACGCACATCTTTAGCATCGTTAATG

CTGCCCCCGAAGGGTTAGTCTTCCTGCACACTGTGCTCCTTCCTACCC

AGTATAAAGATGTCGAAGCATGGTCTGGGCTCTGTGTCGATGGAACT

AACGGTTATGTCCTTCGACAGCCAAACCTCGCTCTCTATAAAGAAGG

GAATTACTATAGGATCACCTCAAGAATCATGTTCGAGCCCAGGATAC

CAACAATGGCCGATTTTGTGCAGATTGAAAATTGTAACGTGACCTTT

GTGAATATCAGTCGATCCGAGCTTCAAACGATTGTTCCTGAGTACAT

CGACGTGAATAAAACTCTACAAGAGCTGTCCTATAAACTGCCTAATT

ATACCGTGCCTGACCTTGTAGTCGAGCAATACAACCAGACTATTCTG

AACCTGACATCGGAAATCTCTACATTGGAGAATAAAAGCGCCGAGC

TCAATTACACAGTGCAGAAGCTGCAGACCCTGATCGACAATATTAAC

AGCACTCTTGTGGACTTAAAGTGGCTGAACCGTGTGGAGACTTACAT

CAAGTGGCCCTGGTGGGTGTGGCTCTGTATTTCCGTGGTCCTTATATT

TGTTGTAAGTATGCTGCTCCTGagcttctggatgtgctctaatgggtctctacagtgtagaata

tgtattTGA

PDI-229E-wtTMCT-AA(SEQ ID NO：153)

MAKNVAIFGLLFSLLVLVPSQIFAQTTNGLNTSYSVCNGCVGYSENVFA

VESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRF

TTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYG

VVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPK

TVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASY

ADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPV

SIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKG

PLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSV

CFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEG

VSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGF

KDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPK

FFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPANVSYDSVSAIVTAN

LSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSAC

KTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLP

TSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQY

YNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLN

YVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTV

ATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDPPQAD

QQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSK

RYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGT

NGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNI

SRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEIS

TLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVW

LCISVVLIFVVSMLLLCCCSTGCCGFFSCFASSIRGCCESTKLPYYDVEKI

HIQ

PDI-229E-H5iTMCT-AA(SEQ ID NO：154)

MAKNVAIFGLLFSLLVLVPSQIFAQTTNGLNTSYSVCNGCVGYSENVFA

VESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRF

TTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYG

VVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPK

TVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASY

ADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPV

SIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKG

PLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSV

CFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEG

VSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGF

KDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPK

FFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPANVSYDSVSAIVTAN

LSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSAC

KTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLP

TSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQY

YNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLN

YVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTV

ATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDPPQAD

QQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSK

RYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGT

NGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNI

SRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEIS

TLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWQIL

SIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

PDI-229E-H5iCT-AA(SEQ ID NO：155)

MAKNVAIFGLLFSLLVLVPSQIFAQTTNGLNTSYSVCNGCVGYSENVFA

VESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRF

TTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYG

VVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPK

TVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASY

ADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPV

SIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKG

PLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSV

CFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEG

VSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGF

KDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPK

FFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPANVSYDSVSAIVTAN

LSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSAC

KTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLP

TSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQY

YNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLN

YVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTV

ATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDPPQAD

QQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSK

RYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGT

NGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNI

SRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEIS

TLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVW

LCISVVLIFVVSMLLLSLWMCSNGSLQCRICI

PDI-229E-H5iCT(V4)-AA(SEQ ID NO：156)

MAKNVAIFGLLFSLLVLVPSQIFAQTTNGLNTSYSVCNGCVGYSENVFA

VESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRF

TTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYG

VVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPK

TVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASY

ADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPV

SIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKG

PLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSV

CFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEG

VSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGF

KDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPK

FFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPANVSYDSVSAIVTAN

LSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSAC

KTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLP

TSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQY

YNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLN

YVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTV

ATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDPPQAD

QQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSK

RYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGT

NGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNI

SRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEIS

TLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVW

LCISVVLIFVVSMLLLCCSNGSLQCRICI

PDI-229E-H1cCT-AA(SEQ ID NO：157)

MAKNVAIFGLLFSLLVLVPSQIFAQTTNGLNTSYSVCNGCVGYSENVFA

VESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRF

TTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYG

VVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPK

TVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASY

ADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPV

SIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKG

PLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSV

CFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEG

VSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGF

KDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPK

FFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPANVSYDSVSAIVTAN

LSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSAC

KTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLP

TSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQY

YNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLN

YVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTV

ATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDPPQAD

QQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSK

RYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGT

NGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNI

SRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEIS

TLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVW

LCISVVLIFVVSMLLLSFWMCSNGSLQCRICI

Natural OC43-CoV S protein wtTM/CT AA (AVR 40344) (SEQ ID NO: 158) MFLILLISLPTAFAVIGDLNCTLDPRLKGSFNNRDTGPPSISIDTVDVTNGLGTYYVLDRVYLNTTLFLNGYYPTSGSTYRNMALKGTDLLSTLWFKPPFLSDFINGIFAKVKNTKVFKDGVMYSEFPAITIGSTFVNTSYSVVVQPRTINSTQDGVNKLQGLLEVSVCQYNMCEYPHTICHPNLGNHFKELWHYDTGVVSCLYKRNFTYDVNATYLYFHFYQEGGTFYAYFTDTGFVTKFLFNVYLGMALSHYYVMPLTCIRRPKDGFSLEYWVTPLTPRQYLLAFNQDGIIFNAVDCMSDFMSEIKCKTQSIAPPTGVYELNGYTVQPVADVYRRKPDLPNCNIEAWLNDKSVPSPLNWERKTFSNCNFNMSSLMSFIQADSFTCNNIDAAKIYGMCFSSITIDKFAIPNRRKVDLQLGNLGYLQSSNYRIDTTATSCQLYYNLPAANVSVSRFNPSTWNKRFGFIEDSVFVPQPTGVFTNHSVVYAQHCFKAPKNFCPCSSCSCPGKNNGIGTCPAGTNSLTCDNLCTLDPITLKAPDTYKCPQSKSLVGIGEHCSGLAVKSDYCGNNSCTCQPQAFLGWSADSCLQGDKCNIFANFILHDVNNGLTCSTDLQKANTEIELGVCVNYDLYGISGQGIFVEVNATYYNSWQNLLYDSNGNLYGFRDYITNRTFMIHSCYSGRVSAAYHANSSEPALLFRNIKCNYVFNNSLTRQLQPINYSFDSYLGCVVNAYNSTAISVQTCDLTVGSGYCVDYSKNRRSRRAITTGYRFTNFEPFTVNSVNDSLEPVGGLYEIQIPSEFTIGNMEEFIQTSSPKVTIDCAAFVCGDYAACKLQLVEYGSFCDNINAILTEVNELLDTTQLQVANSLMNGVTLSTKLKDGVNFNVDDINFSPVLGCLGSECSKASSRSAIEDLLFDKVKLSDVGFVEAYNNCTGGAEIRDLICVQSYKGIKVLPPLLSENQISGYTLAATSASLFPPWTAAAGVPFYLNVQYRINGLGVTMDVLSQNQKLIANAFNNALHAIQQGFDATNSALVKIQAVVNANAEALNNLLQQLSNRFGAISASLQEILSRLDALEAEAQIDRLINGRLTALNAYVSQQLSDSTLVKFSAAQAMEKVNECVKSQSSRINFCGNGNHIISLVQNAPYGLYFIHFNYVPTKYVTAKVSPGLCIAGNRGIAPKSGYFVNVNNTWMYTGSGYYYPEPITENNVVVMSTCAVNYTKAPYVMLNTSIPNLPDFKEELDQWFKNQTSVAPDLSLDYINVTFLDLQVEMNRLQEAIKVLNHSYINLKDIGTYEYYVKWPWYVWLLICLAGVAMLVLLFFICCCTGCGTSCFKKCGGCCDDYTGYQELVIKTSHDD

Natural 229E S protein wtTM/CT AA (P15423) (SEQ ID NO: 159)

MFVLLVAYALLHIAGCQTTNGLNTSYSVCNGCVGYSENVFAVESGGYI

PSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRFTTGFVYF

NGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYGVVVFYCT

NNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPKTVREFVIS

RTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASYADVLVNV

SQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPVSIVSLPVY

HKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKGPLCVDTSH

FTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSVCFSLKDIPG

GCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEGVSSFMNVT

LDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGFKDVTKGTI

YSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPKFFYASNGT

YNCTDAVLTYSSFGVCADGSIIAVQPRNVSYDSVSAIVTANLSIPSNWTT

SVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSACKTIEDALRN

SARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLPTSGSRVAGR

SAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQYYNGIMVLPG

VADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLNYVALQTDVL

QENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTVATALNKIQD

VVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDTIQADQQVDRLITGR

LAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSKRYGFCGNGT

HIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGTNGYVLRQPN

LALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNISRSELQTIVP

EYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEISTLENKSAEL

NYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVWLCISVVLIFV

VSMLLLCCCSTGCCGFFSCFASSIRGCCESTKLPYYDVEKIHIQ Natural OC43-CoV S protein wtTM/CTA (AVR 40344), signal-free peptide (SEQ ID NO: 160)

VIGDLNCTLDPRLKGSFNNRDTGPPSISIDTVDVTNGLGTYYVLDRVYL

NTTLFLNGYYPTSGSTYRNMALKGTDLLSTLWFKPPFLSDFINGIFAKV

KNTKVFKDGVMYSEFPAITIGSTFVNTSYSVVVQPRTINSTQDGVNKLQ

GLLEVSVCQYNMCEYPHTICHPNLGNHFKELWHYDTGVVSCLYKRNFT

YDVNATYLYFHFYQEGGTFYAYFTDTGFVTKFLFNVYLGMALSHYYV

MPLTCIRRPKDGFSLEYWVTPLTPRQYLLAFNQDGIIFNAVDCMSDFMS

EIKCKTQSIAPPTGVYELNGYTVQPVADVYRRKPDLPNCNIEAWLNDKS

VPSPLNWERKTFSNCNFNMSSLMSFIQADSFTCNNIDAAKIYGMCFSSIT

IDKFAIPNRRKVDLQLGNLGYLQSSNYRIDTTATSCQLYYNLPAANVSV

SRFNPSTWNKRFGFIEDSVFVPQPTGVFTNHSVVYAQHCFKAPKNFCPC

SSCSCPGKNNGIGTCPAGTNSLTCDNLCTLDPITLKAPDTYKCPQSKSLV

GIGEHCSGLAVKSDYCGNNSCTCQPQAFLGWSADSCLQGDKCNIFANFI

LHDVNNGLTCSTDLQKANTEIELGVCVNYDLYGISGQGIFVEVNATYY

NSWQNLLYDSNGNLYGFRDYITNRTFMIHSCYSGRVSAAYHANSSEPA

LLFRNIKCNYVFNNSLTRQLQPINYSFDSYLGCVVNAYNSTAISVQTCD

LTVGSGYCVDYSKNRRSRRAITTGYRFTNFEPFTVNSVNDSLEPVGGLY

EIQIPSEFTIGNMEEFIQTSSPKVTIDCAAFVCGDYAACKLQLVEYGSFCD

NINAILTEVNELLDTTQLQVANSLMNGVTLSTKLKDGVNFNVDDINFSP

VLGCLGSECSKASSRSAIEDLLFDKVKLSDVGFVEAYNNCTGGAEIRDLI

CVQSYKGIKVLPPLLSENQISGYTLAATSASLFPPWTAAAGVPFYLNVQ

YRINGLGVTMDVLSQNQKLIANAFNNALHAIQQGFDATNSALVKIQAV

VNANAEALNNLLQQLSNRFGAISASLQEILSRLDALEAEAQIDRLINGRL

TALNAYVSQQLSDSTLVKFSAAQAMEKVNECVKSQSSRINFCGNGNHII

SLVQNAPYGLYFIHFNYVPTKYVTAKVSPGLCIAGNRGIAPKSGYFVNV

NNTWMYTGSGYYYPEPITENNVVVMSTCAVNYTKAPYVMLNTSIPNLP

DFKEELDQWFKNQTSVAPDLSLDYINVTFLDLQVEMNRLQEAIKVLNH

SYINLKDIGTYEYYVKWPWYVWLLICLAGVAMLVLLFFICCCTGCGTS

CFKKCGGCCDDYTGYQELVIKTSHDD

Natural 229E S protein wtTM/CT AA (P15423), NO signal peptide (SEQ ID NO: 161) QTTNGLNTSYSVCNGCVGYSENVFAVESGGYIPSDFAFNNWFLLTNTSSVVDGVVRSFQPLLLNCLWSVSGLRFTTGFVYFNGTGRGDCKGFSSDVLSDVIRYNLNFEENLRRGTILFKTSYGVVVFYCTNNTLVSGDAHIPFGTVLGNFYCFVNTTIGNETTSAFVGALPKTVREFVISRTGHFYINGYRYFTLGNVEAVNFNVTTAETTDFCTVALASYADVLVNVSQTSIANIIYCNSVINRLRCDQLSFDVPDGFYSTSPIQSVELPVSIVSLPVYHKHTFIVLYVDFKPQSGGGKCFNCYPAGVNITLANFNETKGPLCVDTSHFTTKYVAVYANVGRWSASINTGNCPFSFGKVNNFVKFGSVCFSLKDIPGGCAMPIVANWAYSKYYTIGSLYVSWSDGDGITGVPQPVEGVSSFMNVTLDKCTKYNIYDVSGVGVIRVSNDTFLNGITYTSTSGNLLGFKDVTKGTIYSITPCNPPDQLVVYQQAVVGAMLSENFTSYGFSNVVELPKFFYASNGTYNCTDAVLTYSSFGVCADGSIIAVQPRNVSYDSVSAIVTANLSIPSNWTTSVQVEYLQITSTPIVVDCSTYVCNGNVRCVELLKQYTSACKTIEDALRNSARLESADVSEMLTFDKKAFTLANVSSFGDYNLSSVIPSLPTSGSRVAGRSAIEDILFSKLVTSGLGTVDADYKKCTKGLSIADLACAQYYNGIMVLPGVADAERMAMYTGSLIGGIALGGLTSAVSIPFSLAIQARLNYVALQTDVLQENQKILAASFNKAMTNIVDAFTGVNDAITQTSQALQTVATALNKIQDVVNQQGNSLNHLTSQLRQNFQAISSSIQAIYDRLDTIQADQQVDRLITGRLAALNVFVSHTLTKYTEVRASRQLAQQKVNECVKSQSKRYGFCGNGTHIFSIVNAAPEGLVFLHTVLLPTQYKDVEAWSGLCVDGTNGYVLRQPNLALYKEGNYYRITSRIMFEPRIPTMADFVQIENCNVTFVNISRSELQTIVPEYIDVNKTLQELSYKLPNYTVPDLVVEQYNQTILNLTSEISTLENKSAELNYTVQKLQTLIDNINSTLVDLKWLNRVETYIKWPWWVWLCISVVLIFVVSMLLLCCCSTGCCGFFSCFASSIRGCCESTKLPYYDVEKIHIQ

Modified PDI-OC43-COV wtTMCT-AA TMCT region (SEQ ID NO: 162)

WYVWLLICLAGVAMLVLLFFICCCTGCGTSCFKKCGGCCDDYTGYQELVIKTSHDD

Modified PDI-OC43-COV H5iTMCT-AA TMCT region (SEQ ID NO: 163)

WYQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

Modified PDI-OC43-COV H5iCT-AA TMCT region (SEQ ID NO: 164)

WYVWLLICLAGVAMLVLLFFISLWMCSNGSLQCRICI

Modified PDI-OC43-COV H5iCT (V4) -AA TMCT region (SEQ ID NO: 165)

WYVWLLICLAGVAMLVLLFFICCSNGSLQCRICI

Modified PDI-OC43-COV H1cCT-AA TMCT region (SEQ ID NO: 166)

WYVWLLICLAGVAMLVLLFFISFWMCSNGSLQCRICI

Modified PDI-229E-wtTMCT-AA TMCT region (SEQ ID NO: 167)

WWVWLCISVVLIFVVSMLLLCCCSTGCCGFFSCFASSIRGCCESTKLPYYDVEKIHIQ

Modified PDI-229E-H5iTMCT-AA TMCT region (SEQ ID NO: 168)

WWQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

Modified PDI-229E-H5iCT-AA TMCT region (SEQ ID NO: 169)

WWVWLCISVVLIFVVSMLLLSLWMCSNGSLQCRICI

Modified PDI-229E-H5iCT (V4) -AA TMCT region (SEQ ID NO: 170)

WWVWLCISVVLIFVVSMLLLCCSNGSLQCRICI

Modified PDI-229E-H1cCT-AA TMCT region (SEQ ID NO: 171)

WWVWLCISVVLIFVVSMLLLSFWMCSNGSLQCRICI

Modified OC43-CoV S protein TM/CT region with intermediate peptide sequence Xn (SEQ ID NO: 172)

WYVWLLICLAGVAMLVLLFFI-(X)n–csngsXXCXICI

Modified OC43-CoV S protein TM/CT region with intermediate peptide sequence Xn (SEQ ID NO: 173)

WWVWLCISVVLIFVVSMLLL-(X)n–csngsXXCXICI

All references are incorporated herein by reference.

The present invention has been described with respect to one or more embodiments. However, it will be apparent to a person skilled in the art that several changes and modifications may be made without departing from the scope of the invention as defined in the claims.

Sequence listing

<110> mideca Kagaku Co Ltd

<120> modified viral structural proteins

<130> V815385WO

<141> 2023-04-19

<150> US 63/073,327

<151> 2020-09-01

<150> US 63/211,716

<151> 2021-06-17

<160> 173

<170> SIPOSequenceListing 1.0

<210> 1

<211> 1273

<212> PRT

<213> SARS-CoV-2

<400> 1

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr

145 150 155 160

Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

165 170 175

Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe

180 185 190

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu

210 215 220

Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser

245 250 255

Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro

260 265 270

Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala

275 280 285

Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys

290 295 300

Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val

305 310 315 320

Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys

325 330 335

Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala

340 345 350

Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu

355 360 365

Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro

370 375 380

Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe

385 390 395 400

Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly

405 410 415

Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys

420 425 430

Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn

435 440 445

Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe

450 455 460

Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys

465 470 475 480

Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly

485 490 495

Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val

500 505 510

Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys

515 520 525

Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn

530 535 540

Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu

545 550 555 560

Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val

565 570 575

Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe

580 585 590

Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val

595 600 605

Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile

610 615 620

His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser

625 630 635 640

Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val

645 650 655

Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala

660 665 670

Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala

675 680 685

Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser

690 695 700

Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile

705 710 715 720

Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val

725 730 735

Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu

740 745 750

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr

755 760 765

Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln

770 775 780

Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe

785 790 795 800

Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser

805 810 815

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

820 825 830

Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

835 840 845

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

850 855 860

Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

865 870 875 880

Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

915 920 925

Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

930 935 940

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

945 950 955 960

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln

980 985 990

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

995 1000 1005

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu

1010 1015 1020

Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val

1025 1030 1035 1040

Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1045 1050 1055

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu

1060 1065 1070

Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His

1075 1080 1085

Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val

1090 1095 1100

Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr

1105 1110 1115 1120

Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr

1125 1130 1135

Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu

1140 1145 1150

Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp

1155 1160 1165

Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp

1170 1175 1180

Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu

1185 1190 1195 1200

Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile

1205 1210 1215

Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile

1220 1225 1230

Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys

1235 1240 1245

Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val

1250 1255 1260

Leu Lys Gly Val Lys Leu His Tyr Thr

1265 1270

<210> 2

<211> 1258

<212> PRT

<213> SARS-CoV-2

<400> 2

Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser

1 5 10 15

Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val

20 25 30

Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr

35 40 45

Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe

50 55 60

Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr

65 70 75 80

Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp

85 90 95

Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val

100 105 110

Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val

115 120 125

Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val

130 135 140

Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe

145 150 155 160

Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu

165 170 175

Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His

180 185 190

Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu

195 200 205

Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln

210 215 220

Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser

225 230 235 240

Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln

245 250 255

Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp

260 265 270

Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu

275 280 285

Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg

290 295 300

Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu

305 310 315 320

Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr

325 330 335

Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val

340 345 350

Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser

355 360 365

Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser

370 375 380

Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr

385 390 395 400

Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly

405 410 415

Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly

420 425 430

Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro

435 440 445

Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro

450 455 460

Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr

465 470 475 480

Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val

485 490 495

Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro

500 505 510

Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe

515 520 525

Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe

530 535 540

Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala

545 550 555 560

Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser

565 570 575

Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln

580 585 590

Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala

595 600 605

Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly

610 615 620

Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His

625 630 635 640

Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys

645 650 655

Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val

660 665 670

Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn

675 680 685

Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr

690 695 700

Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser

705 710 715 720

Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn

725 730 735

Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu

740 745 750

Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala

755 760 765

Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly

770 775 780

Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg

785 790 795 800

Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala

805 810 815

Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg

820 825 830

Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro

835 840 845

Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala

850 855 860

Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln

865 870 875 880

Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val

885 890 895

Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe

900 905 910

Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser

915 920 925

Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu

930 935 940

Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser

945 950 955 960

Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val

965 970 975

Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr

980 985 990

Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

995 1000 1005

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg

1010 1015 1020

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser

1025 1030 1035 1040

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1045 1050 1055

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala

1060 1065 1070

His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe

1075 1080 1085

Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn

1090 1095 1100

Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn

1105 1110 1115 1120

Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu

1125 1130 1135

Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly

1140 1145 1150

Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile

1155 1160 1165

Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp

1170 1175 1180

Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr

1185 1190 1195 1200

Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr

1205 1210 1215

Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys

1220 1225 1230

Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1235 1240 1245

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1250 1255

<210> 3

<211> 568

<212> PRT

<213> influenza

<400> 3

Met Glu Lys Ile Val Leu Leu Leu Ala Ile Val Ser Leu Val Lys Ser

1 5 10 15

Asp Gln Ile Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Glu Gln Val

20 25 30

Asp Thr Ile Met Glu Lys Asn Val Thr Val Thr His Ala Gln Asp Ile

35 40 45

Leu Glu Lys Thr His Asn Gly Lys Leu Cys Asp Leu Asp Gly Val Lys

50 55 60

Pro Leu Ile Leu Arg Asp Cys Ser Val Ala Gly Trp Leu Leu Gly Asn

65 70 75 80

Pro Met Cys Asp Glu Phe Ile Asn Val Pro Glu Trp Ser Tyr Ile Val

85 90 95

Glu Lys Ala Asn Pro Thr Asn Asp Leu Cys Tyr Pro Gly Ser Phe Asn

100 105 110

Asp Tyr Glu Glu Leu Lys His Leu Leu Ser Arg Ile Asn His Phe Glu

115 120 125

Lys Ile Gln Ile Ile Pro Lys Ser Ser Trp Ser Asp His Glu Ala Ser

130 135 140

Ser Gly Val Ser Ser Ala Cys Pro Tyr Leu Gly Ser Pro Ser Phe Phe

145 150 155 160

Arg Asn Val Val Trp Leu Ile Lys Lys Asn Ser Thr Tyr Pro Thr Ile

165 170 175

Lys Lys Ser Tyr Asn Asn Thr Asn Gln Glu Asp Leu Leu Val Leu Trp

180 185 190

Gly Ile His His Pro Asn Asp Ala Ala Glu Gln Thr Arg Leu Tyr Gln

195 200 205

Asn Pro Thr Thr Tyr Ile Ser Ile Gly Thr Ser Thr Leu Asn Gln Arg

210 215 220

Leu Val Pro Lys Ile Ala Thr Arg Ser Lys Val Asn Gly Gln Ser Gly

225 230 235 240

Arg Met Glu Phe Phe Trp Thr Ile Leu Lys Pro Asn Asp Ala Ile Asn

245 250 255

Phe Glu Ser Asn Gly Asn Phe Ile Ala Pro Glu Tyr Ala Tyr Lys Ile

260 265 270

Val Lys Lys Gly Asp Ser Ala Ile Met Lys Ser Glu Leu Glu Tyr Gly

275 280 285

Asn Cys Asn Thr Lys Cys Gln Thr Pro Met Gly Ala Ile Asn Ser Ser

290 295 300

Met Pro Phe His Asn Ile His Pro Leu Thr Ile Gly Glu Cys Pro Lys

305 310 315 320

Tyr Val Lys Ser Asn Arg Leu Val Leu Ala Thr Gly Leu Arg Asn Ser

325 330 335

Pro Gln Arg Glu Ser Arg Arg Lys Lys Arg Gly Leu Phe Gly Ala Ile

340 345 350

Ala Gly Phe Ile Glu Gly Gly Trp Gln Gly Met Val Asp Gly Trp Tyr

355 360 365

Gly Tyr His His Ser Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Lys

370 375 380

Glu Ser Thr Gln Lys Ala Ile Asp Gly Val Thr Asn Lys Val Asn Ser

385 390 395 400

Ile Ile Asp Lys Met Asn Thr Gln Phe Glu Ala Val Gly Arg Glu Phe

405 410 415

Asn Asn Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Met Glu Asp

420 425 430

Gly Phe Leu Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Met

435 440 445

Glu Asn Glu Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu

450 455 460

Tyr Asp Lys Val Arg Leu Gln Leu Arg Asp Asn Ala Lys Glu Leu Gly

465 470 475 480

Asn Gly Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Glu Cys Met Glu

485 490 495

Ser Ile Arg Asn Gly Thr Tyr Asn Tyr Pro Gln Tyr Ser Glu Glu Ala

500 505 510

Arg Leu Lys Arg Glu Glu Ile Ser Gly Val Lys Leu Glu Ser Ile Gly

515 520 525

Thr Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala

530 535 540

Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

545 550 555 560

Ser Leu Gln Cys Arg Ile Cys Ile

565

<210> 4

<211> 1729

<212> DNA

<213> influenza

<400> 4

ctgtaaaaat ggagaaaata gtgcttcttc ttgcaatagt cagtcttgtt aaaagtgatc 60

agatttgcat tggttaccat gcaaacaatt caacagagca ggttgacaca atcatggaaa 120

agaacgttac tgttacacat gcccaagaca tactggaaaa gacacacaac gggaagctct 180

gcgatctaga tggagtgaag cctctaattt taagagattg tagtgtagct ggatggctcc 240

tcgggaaccc aatgtgtgac gaattcatca atgtaccgga atggtcttac atagtggaga 300

aggccaatcc aaccaatgac ctctgttacc cagggagttt caacgactat gaagaactga 360

aacacctatt gagcagaata aaccattttg agaaaattca aatcatcccc aaaagttctt 420

ggtccgatca tgaagcctca tcaggagtga gctcagcatg tccatacctg ggaagtccct 480

ccttttttag aaatgtggta tggcttatca aaaagaacag tacataccca acaataaaga 540

aaagctacaa taataccaac caagaagatc ttttggtact gtggggaatt caccatccta 600

atgatgcggc agagcagaca aggctatatc aaaacccaac cacctatatt tccattggga 660

catcaacact aaaccagaga ttggtaccaa aaatagctac tagatccaaa gtaaacgggc 720

aaagtggaag gatggagttc ttctggacaa ttttaaaacc taatgatgca atcaacttcg 780

agagtaatgg aaatttcatt gctccagaat atgcatacaa aattgtcaag aaaggggact 840

cagcaattat gaaaagtgaa ttggaatatg gtaactgcaa caccaagtgt caaactccaa 900

tgggggcgat aaactctagt atgccattcc acaacataca ccctctcacc atcggggaat 960

gccccaaata tgtgaaatca aacagattag tccttgcaac agggctcaga aatagccctc 1020

aaagagagag cagaagaaaa aagagaggac tatttggagc tatagcaggt tttatagagg 1080

gaggatggca gggaatggta gatggttggt atgggtacca ccatagcaat gagcagggga 1140

gtgggtacgc tgcagacaaa gaatccactc aaaaggcaat agatggagtc accaataagg 1200

tcaactcaat cattgacaaa atgaacactc agtttgaggc cgttggaagg gaatttaata 1260

acttagaaag gagaatagag aatttaaaca agaagatgga agacgggttt ctagatgtct 1320

ggacttataa tgccgaactt ctggttctca tggaaaatga gagaactcta gactttcatg 1380

actcaaatgt taagaacctc tacgacaagg tccgactaca gcttagggat aatgcaaagg 1440

agctgggtaa cggttgtttc gagttctatc acaaatgtga taatgaatgt atggaaagta 1500

taagaaacgg aacgtacaac tatccgcagt attcagaaga agcaagatta aaaagagagg 1560

aaataagtgg ggtaaaattg gaatcaatag gaacttacca aatactgtca atttattcaa 1620

cagtggcgag ttccctagca ctggcaatca tgatggctgg tctatcttta tggatgtgct 1680

ccaatggatc gttacaatgc agaatttgca tttaaatttg tgagttcag 1729

<210> 5

<211> 1250

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2 with H5A/Indonesia/5/05 hemagglutinin CT AA

<400> 5

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe

20 25 30

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu

35 40 45

His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp

50 55 60

Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp

65 70 75 80

Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu

85 90 95

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser

100 105 110

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile

115 120 125

Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr

130 135 140

Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr

145 150 155 160

Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu

165 170 175

Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe

180 185 190

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr

195 200 205

Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu

210 215 220

Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr

225 230 235 240

Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser

245 250 255

Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro

260 265 270

Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala

275 280 285

Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys

290 295 300

Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val

305 310 315 320

Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys

325 330 335

Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala

340 345 350

Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu

355 360 365

Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro

370 375 380

Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe

385 390 395 400

Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly

405 410 415

Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys

420 425 430

Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn

435 440 445

Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe

450 455 460

Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys

465 470 475 480

Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly

485 490 495

Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val

500 505 510

Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys

515 520 525

Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn

530 535 540

Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu

545 550 555 560

Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val

565 570 575

Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe

580 585 590

Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val

595 600 605

Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile

610 615 620

His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser

625 630 635 640

Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val

645 650 655

Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala

660 665 670

Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala

675 680 685

Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser

690 695 700

Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile

705 710 715 720

Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val

725 730 735

Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu

740 745 750

Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr

755 760 765

Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln

770 775 780

Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe

785 790 795 800

Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser

805 810 815

Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly

820 825 830

Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

835 840 845

Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

850 855 860

Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

865 870 875 880

Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

915 920 925

Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

930 935 940

Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

945 950 955 960

Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln

980 985 990

Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

995 1000 1005

Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu

1010 1015 1020

Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val

1025 1030 1035 1040

Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1045 1050 1055

Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu

1060 1065 1070

Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His

1075 1080 1085

Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val

1090 1095 1100

Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr

1105 1110 1115 1120

Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr

1125 1130 1135

Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu

1140 1145 1150

Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp

1155 1160 1165

Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp

1170 1175 1180

Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu

1185 1190 1195 1200

Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile

1205 1210 1215

Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile

1220 1225 1230

Met Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

1235 1240 1245

Cys Ile

1250

<210> 6

<211> 50

<212> PRT

<213> influenza

<400> 6

Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Ile Tyr Gln Ile Leu Ala

1 5 10 15

Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val Val Ser Leu Gly

20 25 30

Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

35 40 45

Cys Ile

50

<210> 7

<211> 50

<212> PRT

<213> influenza

<400> 7

Ile Lys Gly Val Lys Leu Ser Ser Met Gly Val Tyr Gln Ile Leu Ala

1 5 10 15

Ile Tyr Ala Thr Val Ala Gly Ser Leu Ser Leu Ala Ile Met Met Ala

20 25 30

Gly Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

35 40 45

Cys Ile

50

<210> 8

<211> 49

<212> PRT

<213> influenza

<400> 8

Ile Lys Gly Val Glu Leu Lys Ser Gly Tyr Lys Asp Trp Ile Leu Trp

1 5 10 15

Ile Ser Phe Ala Ile Ser Cys Phe Leu Leu Cys Val Ala Leu Leu Gly

20 25 30

Phe Ile Met Trp Ala Cys Gln Lys Gly Asn Ile Arg Cys Asn Ile Cys

35 40 45

Ile

<210> 9

<211> 50

<212> PRT

<213> influenza

<400> 9

Ile Ser Gly Val Lys Leu Glu Ser Ile Gly Thr Tyr Gln Ile Leu Ser

1 5 10 15

Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala Leu Ala Ile Met Met Ala

20 25 30

Gly Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

35 40 45

Cys Ile

50

<210> 10

<211> 50

<212> PRT

<213> influenza

<400> 10

Ile Glu Ser Val Lys Leu Glu Asn Leu Gly Val Tyr Gln Ile Leu Ala

1 5 10 15

Ile Tyr Ser Thr Val Ser Ser Ser Leu Val Leu Val Gly Leu Ile Met

20 25 30

Ala Met Gly Leu Trp Met Cys Ser Asn Gly Ser Met Gln Cys Arg Ile

35 40 45

Cys Ile

50

<210> 11

<211> 49

<212> PRT

<213> influenza

<400> 11

Ile Asp Pro Val Lys Leu Ser Ser Gly Tyr Lys Asp Val Ile Leu Trp

1 5 10 15

Phe Ser Phe Gly Ala Ser Cys Phe Ile Leu Leu Ala Ile Val Met Gly

20 25 30

Leu Val Phe Ile Cys Val Lys Asn Gly Asn Met Arg Cys Thr Ile Cys

35 40 45

Ile

<210> 12

<211> 50

<212> PRT

<213> influenza

<400> 12

Ile Glu Gly Val Lys Leu Glu Ser Glu Gly Thr Tyr Lys Ile Leu Thr

1 5 10 15

Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Ala Met Gly Phe Ala

20 25 30

Ala Phe Leu Phe Trp Ala Met Ser Asn Gly Ser Cys Arg Cys Asn Ile

35 40 45

Cys Ile

50

<210> 13

<211> 50

<212> PRT

<213> influenza

<400> 13

Ala Ala Ser Leu Asn Asp Asp Gly Leu Asp Asn His Thr Ile Leu Leu

1 5 10 15

Tyr Tyr Ser Thr Ala Ala Ser Ser Leu Ala Val Thr Leu Met Ile Ala

20 25 30

Ile Phe Val Val Tyr Met Val Ser Arg Asp Asn Val Ser Cys Ser Ile

35 40 45

Cys Leu

50

<210> 14

<211> 50

<212> PRT

<213> artificial sequence

<220>

<223> consensus sequence of C-terminal region of influenza hemagglutinin

<220>

<221> misc_feature

<222> (2)..(2)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (7)..(7)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (9)..(9)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (11)..(11)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (13)..(13)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (16)..(16)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (26)..(26)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (28)..(36)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (44)..(45)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (47)..(47)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (2)..(2)

<223> The 'Xaa' at location 2 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (7)..(7)

<223> The 'Xaa' at location 7 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (9)..(9)

<223> The 'Xaa' at location 9 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (11)..(11)

<223> The 'Xaa' at location 11 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (13)..(13)

<223> The 'Xaa' at location 13 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (16)..(16)

<223> The 'Xaa' at location 16 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (26)..(26)

<223> The 'Xaa' at location 26 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (28)..(28)

<223> The 'Xaa' at location 28 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (29)..(29)

<223> The 'Xaa' at location 29 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (30)..(30)

<223> The 'Xaa' at location 30 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (31)..(31)

<223> The 'Xaa' at location 31 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (32)..(32)

<223> The 'Xaa' at location 32 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (33)..(33)

<223> The 'Xaa' at location 33 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (34)..(34)

<223> The 'Xaa' at location 34 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (35)..(35)

<223> The 'Xaa' at location 35 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (36)..(36)

<223> The 'Xaa' at location 36 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (44)..(44)

<223> The 'Xaa' at location 44 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (45)..(45)

<223> The 'Xaa' at location 45 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (47)..(47)

<223> The 'Xaa' at location 47 stands for Gln, Arg, Pro, or Leu.

<400> 14

Ile Xaa Gly Val Lys Leu Xaa Ser Xaa Gly Xaa Tyr Xaa Ile Leu Xaa

1 5 10 15

Ile Tyr Ser Thr Val Ala Ser Ser Leu Xaa Leu Xaa Xaa Xaa Xaa Xaa

20 25 30

Xaa Xaa Xaa Xaa Trp Met Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile

35 40 45

Cys Ile

50

<210> 15

<211> 16

<212> PRT

<213> artificial sequence

<220>

<223> consensus sequence of CT Domain of influenza hemagglutinin

<220>

<221> misc_feature

<222> (1)..(2)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (10)..(11)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (13)..(13)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (1)..(1)

<223> The 'Xaa' at location 1 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (2)..(2)

<223> The 'Xaa' at location 2 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (10)..(10)

<223> The 'Xaa' at location 10 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (11)..(11)

<223> The 'Xaa' at location 11 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (13)..(13)

<223> The 'Xaa' at location 13 stands for Gln, Arg, Pro, or Leu.

<400> 15

Xaa Xaa Trp Met Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile Cys Ile

1 5 10 15

<210> 16

<211> 69

<212> PRT

<213> SARS-CoV-2

<400> 16

Trp Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe

1 5 10 15

Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys

20 25 30

Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser

35 40 45

Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val

50 55 60

Lys Leu His Tyr Thr

65

<210> 17

<211> 50

<212> PRT

<213> influenza

<400> 17

Ile Ser Gly Val Lys Leu Glu Ser Ile Gly Thr Tyr Gln Ile Leu Ser

1 5 10 15

Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala Leu Ala Ile Met Met Ala

20 25 30

Gly Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

35 40 45

Cys Ile

50

<210> 18

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2S protein, having the C-terminal region of H5i hemagglutinin CT

<400> 18

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 19

<211> 40

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2S protein, having H5i hemagglutinin CT, C-terminal region of Change 1

<400> 19

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

20 25 30

Ser Leu Gln Cys Arg Ile Cys Ile

35 40

<210> 20

<211> 1258

<212> PRT

<213> artificial sequence

<220>

<223> (SP-free) SARS-CoV-2S protein GSAS+PP wtTM/CT AA

<400> 20

Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser

1 5 10 15

Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val

20 25 30

Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr

35 40 45

Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe

50 55 60

Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr

65 70 75 80

Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp

85 90 95

Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val

100 105 110

Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val

115 120 125

Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val

130 135 140

Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe

145 150 155 160

Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu

165 170 175

Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His

180 185 190

Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu

195 200 205

Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln

210 215 220

Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser

225 230 235 240

Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln

245 250 255

Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp

260 265 270

Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu

275 280 285

Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg

290 295 300

Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu

305 310 315 320

Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr

325 330 335

Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val

340 345 350

Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser

355 360 365

Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser

370 375 380

Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr

385 390 395 400

Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly

405 410 415

Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly

420 425 430

Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro

435 440 445

Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro

450 455 460

Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr

465 470 475 480

Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val

485 490 495

Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro

500 505 510

Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe

515 520 525

Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe

530 535 540

Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala

545 550 555 560

Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser

565 570 575

Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln

580 585 590

Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala

595 600 605

Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly

610 615 620

Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His

625 630 635 640

Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys

645 650 655

Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val

660 665 670

Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn

675 680 685

Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr

690 695 700

Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser

705 710 715 720

Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn

725 730 735

Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu

740 745 750

Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala

755 760 765

Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly

770 775 780

Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg

785 790 795 800

Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala

805 810 815

Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg

820 825 830

Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro

835 840 845

Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala

850 855 860

Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln

865 870 875 880

Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val

885 890 895

Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe

900 905 910

Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser

915 920 925

Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu

930 935 940

Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser

945 950 955 960

Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val

965 970 975

Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr

980 985 990

Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

995 1000 1005

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg

1010 1015 1020

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser

1025 1030 1035 1040

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1045 1050 1055

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala

1060 1065 1070

His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe

1075 1080 1085

Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn

1090 1095 1100

Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn

1105 1110 1115 1120

Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu

1125 1130 1135

Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly

1140 1145 1150

Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile

1155 1160 1165

Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp

1170 1175 1180

Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr

1185 1190 1195 1200

Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr

1205 1210 1215

Ile Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys

1220 1225 1230

Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1235 1240 1245

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1250 1255

<210> 21

<211> 1235

<212> PRT

<213> artificial sequence

<220>

<223> (no SP) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT AA

<400> 21

Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser

1 5 10 15

Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val

20 25 30

Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr

35 40 45

Trp Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe

50 55 60

Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr

65 70 75 80

Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp

85 90 95

Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val

100 105 110

Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val

115 120 125

Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val

130 135 140

Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe

145 150 155 160

Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu

165 170 175

Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His

180 185 190

Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu

195 200 205

Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln

210 215 220

Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser

225 230 235 240

Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln

245 250 255

Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp

260 265 270

Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu

275 280 285

Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg

290 295 300

Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu

305 310 315 320

Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr

325 330 335

Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val

340 345 350

Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser

355 360 365

Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser

370 375 380

Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr

385 390 395 400

Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly

405 410 415

Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly

420 425 430

Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro

435 440 445

Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro

450 455 460

Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr

465 470 475 480

Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val

485 490 495

Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro

500 505 510

Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe

515 520 525

Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe

530 535 540

Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala

545 550 555 560

Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser

565 570 575

Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln

580 585 590

Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala

595 600 605

Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly

610 615 620

Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His

625 630 635 640

Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys

645 650 655

Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Gly Ser Ala Ser Ser Val

660 665 670

Ala Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn

675 680 685

Ser Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr

690 695 700

Ile Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser

705 710 715 720

Val Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn

725 730 735

Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu

740 745 750

Thr Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala

755 760 765

Gln Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly

770 775 780

Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg

785 790 795 800

Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala

805 810 815

Gly Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg

820 825 830

Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro

835 840 845

Leu Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala

850 855 860

Gly Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln

865 870 875 880

Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val

885 890 895

Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe

900 905 910

Asn Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser

915 920 925

Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu

930 935 940

Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser

945 950 955 960

Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Pro Pro Glu Ala Glu Val

965 970 975

Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr

980 985 990

Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

995 1000 1005

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg

1010 1015 1020

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser

1025 1030 1035 1040

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1045 1050 1055

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala

1060 1065 1070

His Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe

1075 1080 1085

Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn

1090 1095 1100

Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn

1105 1110 1115 1120

Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu

1125 1130 1135

Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly

1140 1145 1150

Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile

1155 1160 1165

Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp

1170 1175 1180

Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr

1185 1190 1195 1200

Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr

1205 1210 1215

Ile Met Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg

1220 1225 1230

Ile Cys Ile

1235

<210> 22

<211> 3849

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-CoV-2S protein GSAS+PP wtTM/CT-DNA

<400> 22

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct gctgcatgac ctcttgctgc tcctgtctga aaggctgctg ctcttgcgga 3780

tcctgctgca aatttgatga ggatgacagt gaaccagtcc tgaagggcgt gaagctgcac 3840

tatacttag 3849

<210> 23

<211> 1282

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-CoV-2S protein GSAS+PP wtTM/CT-AA

<400> 23

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser

1235 1240 1245

Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys

1250 1255 1260

Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His

1265 1270 1275 1280

Tyr Thr

<210> 24

<211> 52

<212> DNA

<213> artificial sequence

<220>

<223> IF(PDI)-CoV(opt2).c

<400> 24

tctcagatct tcgcggtgaa tcttacgacg cgaacacagt taccacccgc at 52

<210> 25

<211> 51

<212> DNA

<213> artificial sequence

<220>

<223> IF(AVB)-CoV(opt2).r

<400> 25

acgacacgac taaggcctct aagtatagtg cagcttcacg cccttcagga c 51

<210> 26

<211> 3789

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified SARS-CoV-2S protein GSAS+PP H5iTM/CT-DNA

<400> 26

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atcaaatact gtcaatttat tcaacagtgg cgagttccct agcactggca 3720

atcatgatgg ctggtctatc tttatggatg tgctccaatg gatcgttaca atgcagaatt 3780

tgcatttaa 3789

<210> 27

<211> 1262

<212> PRT

<213> artificial sequence

<220>

<223> PDI-modified SARS-CoV-2S protein GSAS+PP H5iTM/CT-AA

<400> 27

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr

1220 1225 1230

Val Ala Ser Ser Leu Ala Leu Ala Ile Met Met Ala Gly Leu Ser Leu

1235 1240 1245

Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255 1260

<210> 28

<211> 48

<212> DNA

<213> artificial sequence

<220>

<223> IF(Avb)-H5I.r

<400> 28

acgacacgac taaggccttt aaatgcaaat tctgcattgt aacgatcc 48

<210> 29

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified SARS-CoV-2S protein GSAS+PP wtTM/H5iCT-DNA

<400> 29

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 30

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> PDI-modified SARS-CoV-2S protein GSAS+PP wtTM/H5iCT-AA

<400> 30

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 31

<211> 4474

<212> DNA

<213> artificial sequence

<220>

<223> cloning vector 8501 from left to right T-DNA

<400> 31

tggcaggata tattgtggtg taaacaaatt gacgcttaga caacttaata acacattgcg 60

gacgttttta atgtactgaa ttaacgccga atcccgggct ggtatattta tatgttgtca 120

aataactcaa aaaccataaa agtttaagtt agcaagtgtg tacattttta cttgaacaaa 180

aatattcacc tactactgtt ataaatcatt attaaacatt agagtaaaga aatatggatg 240

ataagaacaa gagtagtgat attttgacaa caattttgtt gcaacatttg agaaaatttt 300

gttgttctct cttttcattg gtcaaaaaca atagagagag aaaaaggaag agggagaata 360

aaaacataat gtgagtatga gagagaaagt tgtacaaaag ttgtaccaaa atagttgtac 420

aaatatcatt gaggaatttg acaaaagcta cacaaataag ggttaattgc tgtaaataaa 480

taaggatgac gcattagaga gatgtaccat tagagaattt ttggcaagtc attaaaaaga 540

aagaataaat tatttttaaa attaaaagtt gagtcatttg attaaacatg tgattattta 600

atgaattgat gaaagagttg gattaaagtt gtattagtaa ttagaatttg gtgtcaaatt 660

taatttgaca tttgatcttt tcctatatat tgccccatag agtcagttaa ctcattttta 720

tatttcatag atcaaataag agaaataacg gtatattaat ccctccaaaa aaaaaaaacg 780

gtatatttac taaaaaatct aagccacgta ggaggataac aggatccccg taggaggata 840

acatccaatc caaccaatca caacaatcct gatgagataa cccactttaa gcccacgcat 900

ctgtggcaca tctacattat ctaaatcaca cattcttcca cacatctgag ccacacaaaa 960

accaatccac atctttatca cccattctat aaaaaatcac actttgtgag tctacacttt 1020

gattcccttc aaacacatac aaagagaaga gactaattaa ttaattaatc atcttgagag 1080

aaaatggaac gagctataca aggaaacgac gctagggaac aagctaacag tgaacgttgg 1140

gatggaggat caggaggtac cacttctccc ttcaaacttc ctgacgaaag tccgagttgg 1200

actgagtggc ggctacataa cgatgagacg aattcgaatc aagataatcc ccttggtttc 1260

aaggaaagct ggggtttcgg gaaagttgta tttaagagat atctcagata cgacaggacg 1320

gaagcttcac tgcacagagt ccttggatct tggacgggag attcggttaa ctatgcagca 1380

tctcgatttt tcggtttcga ccagatcgga tgtacctata gtattcggtt tcgaggagtt 1440

agtatcaccg tttctggagg gtcgcgaact cttcagcatc tctgtgagat ggcaattcgg 1500

tctaagcaag aactgctaca gcttgcccca atcgaagtgg aaagtaatgt atcaagagga 1560

tgccctgaag gtactcaaac cttcgaaaaa gaaagcgagt aagttaaaat gcttcttcgt 1620

ctcctattta taatatggtt tgttattgtt aattttgttc ttgtagaaga gcttaattaa 1680

tcgttgttgt tatgaaatac tatttgtatg agatgaactg gtgtaatgta attcatttac 1740

ataagtggag tcagaatcag aatgtttcct ccataactaa ctagacatga agacctgccg 1800

cgtacaattg tcttatattt gaacaactaa aattgaacat cttttgccac aactttataa 1860

gtggttaata tagctcaaat atatggtcaa gttcaataga ttaataatgg aaatatcagt 1920

tatcgaaatt cattaacaat caacttaacg ttattaacta ctaattttat atcatcccct 1980

ttgataaatg atagtacacc aattaggaag gagcatgctc gcctaggaga ttgtcgtttc 2040

ccgccttcag tttgcaagct gctctagccg tgtagccaat acgcaaaccg cctctccccg 2100

cgcgttggga attactagcg cgtgtcgaca agcttgcatg ccggtcaaca tggtggagca 2160

cgacacactt gtctactcca aaaatatcaa agatacagtc tcagaagacc aaagggcaat 2220

tgagactttt caacaaaggg taatatccgg aaacctcctc ggattccatt gcccagctat 2280

ctgtcacttt attgtgaaga tagtggaaaa ggaaggtggc tcctacaaat gccatcattg 2340

cgataaagga aaggccatcg ttgaagatgc ctctgccgac agtggtccca aagatggacc 2400

cccacccacg aggagcatcg tggaaaaaga agacgttcca accacgtctt caaagcaagt 2460

ggattgatgt gataacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga 2520

tacagtctca gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa 2580

cctcctcgga ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga 2640

aggtggctcc tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc 2700

tgccgacagt ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga 2760

cgttccaacc acgtcttcaa agcaagtgga ttgatgtgat atctccactg acgtaaggga 2820

tgacgcacaa tcccactatc cttcgcaaga cccttcctct atataaggaa gttcatttca 2880

tttggagagg cacacaattt gctttagtga ttaaactttc ttttacaaca aattaaaggt 2940

ctattatctc ccaacaacat aagaaaacaa tggcgaaaaa cgttgcgatt ttcggcttat 3000

tgttttctct tcttgtgttg gttccttctc agatcttcgc gacgtcactc ctcagccaaa 3060

acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac taactccatg 3120

gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt gacctggaac 3180

tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc tgacctctac 3240

actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac cgtcacctgc 3300

aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc cagggattgt 3360

ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat cttcccccca 3420

aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt tgtggtagac 3480

atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt ggaggtgcac 3540

acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc agtcagtgaa 3600

cttcccatca tgcaccagga ctggctcaat ggcaaggaga cgtccagatt ttggcgatct 3660

attcaactgt cgccagttca ttggtactgg tagtctccct gggggcaatc agtttctgga 3720

tgtgctctaa tgggtctcta cagtgtagaa tatgtattta aaggccttag tcgtgtcgtt 3780

tttcaaataa tataatcctt ttagggtttt agttagttta aattttctgt tgctcctgtt 3840

tagcaggtcg tgccttcagc aagcacacaa aaacagagtg tttattttaa gttgtttgtt 3900

tagtgattca aaaaaaaaat cgttcaaaca tttggcaata aagtttctta agattgaatc 3960

ctgttgccgg tcttgcgatg attatcatat aatttctgtt gaattacgtt aagcatgtaa 4020

taattaacat gtaatgcatg acgttattta tgagatgggt ttttatgatt agagtcccgc 4080

aattatacat ttaatacgcg atagaaaaca aaatatagcg cgcaaactag gataaattat 4140

cgcgcgcggt gtcatctatg ttactagatc tctagagtct caagcttggc gcgcccacgt 4200

gactagtggc actggccgtc gttttacaac gtcgtgactg ggaaaaccct ggcgttaccc 4260

aacttaatcg ccttgcagca catccccctt tcgccagctg gcgtaatagc gaagaggccc 4320

gcaccgatcg cccttcccaa cagttgcgca gcctgaatgg cgaatgctag agcagcttga 4380

gcttggatca gattgtcgtt tcccgccttc agtttaaact atcagtgttt gacaggatat 4440

attggcgggt aaacctaaga gaaaagagcg ttta 4474

<210> 32

<211> 5083

<212> DNA

<213> artificial sequence

<220>

<223> construct 8586 from 2X35S prom to NOS term

<400> 32

gtcaacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga tacagtctca 60

gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa cctcctcgga 120

ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga aggtggctcc 180

tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc tgccgacagt 240

ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga cgttccaacc 300

acgtcttcaa agcaagtgga ttgatgtgat aacatggtgg agcacgacac acttgtctac 360

tccaaaaata tcaaagatac agtctcagaa gaccaaaggg caattgagac ttttcaacaa 420

agggtaatat ccggaaacct cctcggattc cattgcccag ctatctgtca ctttattgtg 480

aagatagtgg aaaaggaagg tggctcctac aaatgccatc attgcgataa aggaaaggcc 540

atcgttgaag atgcctctgc cgacagtggt cccaaagatg gacccccacc cacgaggagc 600

atcgtggaaa aagaagacgt tccaaccacg tcttcaaagc aagtggattg atgtgatatc 660

tccactgacg taagggatga cgcacaatcc cactatcctt cgcaagaccc ttcctctata 720

taaggaagtt catttcattt ggagaggcac acaatttgct ttagtgatta aactttcttt 780

tacaacaaat taaaggtcta ttatctccca acaacataag aaaacaatgg cgaaaaacgt 840

tgcgattttc ggcttattgt tttctcttct tgtgttggtt ccttctcaga tcttcgcggt 900

gaatcttacg acgcgaacac agttaccacc cgcatataca aatagcttca ctcggggtgt 960

ttattacccc gacaaagtgt tcaggtcctc cgtgctccac tcaacacagg acctctttct 1020

tcctttcttt tctaacgtga catggtttca tgccattcat gtatccggca ctaacggtac 1080

taagaggttc gataatcctg tgctcccttt caatgacggc gtttactttg caagcacaga 1140

gaagagtaac atcatccgag gttggatctt tggcactacc ctcgattcaa agacgcagag 1200

cctcctcatt gtgaacaatg ccactaacgt ggtgatcaaa gtttgcgagt ttcagttctg 1260

caatgaccct ttcttggggg tgtactatca taagaacaac aagtcttgga tggaatctga 1320

attccgcgtc tatagcagcg ccaacaactg cacctttgaa tacgtgtccc agcccttcct 1380

tatggacctg gagggaaagc agggaaactt taagaatctg agagagttcg tgtttaaaaa 1440

tatcgacggc tattttaaga tctattctaa gcacacgcct attaatctcg tgcgcgatct 1500

tccacaaggc ttcagcgccc tggaaccact cgtggacctc ccaattggta tcaacatcac 1560

tagatttcag actctgcttg ccctccaccg atcctatctg acacccggag actcctctag 1620

cggctggact gccggcgctg ccgcttatta cgttggttat cttcagccac gcacgttcct 1680

gctgaagtat aacgagaatg gtactattac cgatgccgtg gattgtgccc ttgaccccct 1740

gtccgaaact aagtgcacac tcaagtcatt cactgtggaa aaaggaatct accagacaag 1800

caattttcgg gtccagccta ctgagagcat tgtgcgcttt cctaacatca caaatctttg 1860

ccccttcgga gaggttttca atgctacacg gtttgcctcc gtgtatgcct ggaaccgcaa 1920

gagaatttcc aattgcgtgg ccgattactc cgtgctctac aatagtgcaa gctttagcac 1980

ctttaagtgc tatggcgtat cccctactaa gcttaacgac ttgtgtttca caaacgtgta 2040

tgccgactcc tttgtgatac ggggcgacga agttagacag atagcaccag gacagacggg 2100

aaagatagct gactacaact ataagcttcc tgatgacttc actggctgcg ttatcgcgtg 2160

gaattctaac aacctggact caaaagtcgg cggcaactat aactatctct atcggctgtt 2220

ccgcaagagt aaccttaagc cctttgagag agatataagc actgaaatct accaggctgg 2280

cagtacgccc tgtaatggcg tggaaggctt taattgttat tttccactgc aatcctatgg 2340

ttttcagcca accaatggcg tgggctacca accataccgc gtcgtggtgc tctcctttga 2400

actgctccac gctcccgcga ctgtctgcgg ccccaagaag tccacgaacc ttgtgaagaa 2460

taagtgcgtt aattttaatt tcaacggcct cactggaaca ggagtgctca ctgagagtaa 2520

caagaagttc ctgccatttc aacaatttgg cagagacata gccgatacta ctgacgccgt 2580

tagggacccc cagaccctcg agattctcga tataacgccc tgctccttcg gtggagtttc 2640

cgtgatcacg ccaggcacca ataccagtaa ccaggtcgcc gtgctgtatc aggatgtcaa 2700

ctgtactgag gtgcccgtag ccatccatgc ggatcagctc acaccaactt ggagggtgta 2760

cagcaccggc tccaatgtat tccagactcg ggccggatgc cttattggcg ccgaacacgt 2820

gaacaatagt tacgaatgcg atattccaat tggcgccgga atctgtgcta gctaccagac 2880

tcagacgaac tccccaggca gcgccagcag cgttgccagc cagtcaatca tcgcttatac 2940

aatgtcactt ggagccgaaa actccgtggc ttactcaaac aacagcatcg ccatccccac 3000

aaacttcacc atatccgtga caactgagat tctgccagtg tccatgacta agacgtccgt 3060

agattgcact atgtacatat gcggcgacag cacagaatgt tctaatctgc tgctgcaata 3120

tggaagcttc tgcactcaac tgaacagagc gctcacaggc atcgccgtgg agcaggataa 3180

gaatacccag gaggtgttcg cccaagttaa gcagatctac aagaccccac ccataaagga 3240

tttcggtgga ttcaatttta gtcagatact cccagaccca tctaagccat ccaagaggag 3300

ctttatcgag gatcttttgt ttaacaaagt tactctggcc gacgccggtt tcatcaagca 3360

gtacggagat tgcctcggcg acatcgctgc tcgtgacctc atctgtgcgc aaaagtttaa 3420

cggtctgacg gtgctgcctc ccctccttac tgatgaaatg atcgcccagt ataccagcgc 3480

actcctcgct ggcaccataa catccggttg gacattcggc gctggtgcag cactgcagat 3540

accattcgcc atgcaaatgg catatcgttt caacggtatc ggtgtcacac agaatgtcct 3600

atatgagaac cagaagctga tcgcaaatca gttcaatagt gccatcggaa aaatccagga 3660

tagccttagc agcacagcct cagcccttgg caaactccag gatgtcgtga accagaatgc 3720

ccaggctctc aataccctcg tgaagcagct ctcatctaat ttcggcgcaa tttccagtgt 3780

cctcaacgac atcctcagcc gcctcgaccc ccccgaggcc gaagtgcaga ttgacagact 3840

gattacaggt cgactccaga gcctccagac ttacgtgact cagcagctga taagagccgc 3900

cgagataagg gccagcgcta acctggctgc cacaaagatg tctgagtgcg tgctgggcca 3960

gtccaagaga gtagacttct gtggcaaagg ctaccatctg atgagcttcc cacaatccgc 4020

acctcacggc gtagtgttcc tccacgtgac atatgtaccg gctcaggaga agaatttcac 4080

taccgctcct gctatatgcc atgatggaaa ggctcacttc ccccgggagg gggtgttcgt 4140

gtccaacggc acccattggt ttgtgactca gcggaatttc tacgaacccc agatcataac 4200

cactgacaac acatttgtgt ccggaaattg tgacgtggtc attggaatag tgaacaacac 4260

tgtttatgat ccactgcagc cagaacttga cagctttaag gaggagctcg acaagtactt 4320

caagaatcat acgtcaccag atgtggacct cggagatatt agcggtatca atgccagtgt 4380

tgtcaatatt cagaaggaaa tagaccgcct taatgaggtc gccaaaaatc tgaacgagag 4440

cctcatcgat cttcaggagc tgggcaaata tgagcagtac atcaagtggc cttggtatat 4500

ttggcttggc ttcatcgccg gcctgatcgc catagtaatg gtcacaatta tgctctgctg 4560

catgacctct tgctgctcct gtctgaaagg ctgctgctct tgcggatcct gctgcaaatt 4620

tgatgaggat gacagtgaac cagtcctgaa gggcgtgaag ctgcactata cttagaggcc 4680

ttagtcgtgt cgtttttcaa ataatataat ccttttaggg ttttagttag tttaaatttt 4740

ctgttgctcc tgtttagcag gtcgtgcctt cagcaagcac acaaaaacag agtgtttatt 4800

ttaagttgtt tgtttagtga ttcaaaaaaa aaatcgttca aacatttggc aataaagttt 4860

cttaagattg aatcctgttg ccggtcttgc gatgattatc atataatttc tgttgaatta 4920

cgttaagcat gtaataatta acatgtaatg catgacgtta tttatgagat gggtttttat 4980

gattagagtc ccgcaattat acatttaata cgcgatagaa aacaaaatat agcgcgcaaa 5040

ctaggataaa ttatcgcgcg cggtgtcatc tatgttacta gat 5083

<210> 33

<211> 4461

<212> DNA

<213> artificial sequence

<220>

<223> cloning vector 8500 from left to right T-DNA

<400> 33

tggcaggata tattgtggtg taaacaaatt gacgcttaga caacttaata acacattgcg 60

gacgttttta atgtactgaa ttaacgccga atcccgggct ggtatattta tatgttgtca 120

aataactcaa aaaccataaa agtttaagtt agcaagtgtg tacattttta cttgaacaaa 180

aatattcacc tactactgtt ataaatcatt attaaacatt agagtaaaga aatatggatg 240

ataagaacaa gagtagtgat attttgacaa caattttgtt gcaacatttg agaaaatttt 300

gttgttctct cttttcattg gtcaaaaaca atagagagag aaaaaggaag agggagaata 360

aaaacataat gtgagtatga gagagaaagt tgtacaaaag ttgtaccaaa atagttgtac 420

aaatatcatt gaggaatttg acaaaagcta cacaaataag ggttaattgc tgtaaataaa 480

taaggatgac gcattagaga gatgtaccat tagagaattt ttggcaagtc attaaaaaga 540

aagaataaat tatttttaaa attaaaagtt gagtcatttg attaaacatg tgattattta 600

atgaattgat gaaagagttg gattaaagtt gtattagtaa ttagaatttg gtgtcaaatt 660

taatttgaca tttgatcttt tcctatatat tgccccatag agtcagttaa ctcattttta 720

tatttcatag atcaaataag agaaataacg gtatattaat ccctccaaaa aaaaaaaacg 780

gtatatttac taaaaaatct aagccacgta ggaggataac aggatccccg taggaggata 840

acatccaatc caaccaatca caacaatcct gatgagataa cccactttaa gcccacgcat 900

ctgtggcaca tctacattat ctaaatcaca cattcttcca cacatctgag ccacacaaaa 960

accaatccac atctttatca cccattctat aaaaaatcac actttgtgag tctacacttt 1020

gattcccttc aaacacatac aaagagaaga gactaattaa ttaattaatc atcttgagag 1080

aaaatggaac gagctataca aggaaacgac gctagggaac aagctaacag tgaacgttgg 1140

gatggaggat caggaggtac cacttctccc ttcaaacttc ctgacgaaag tccgagttgg 1200

actgagtggc ggctacataa cgatgagacg aattcgaatc aagataatcc ccttggtttc 1260

aaggaaagct ggggtttcgg gaaagttgta tttaagagat atctcagata cgacaggacg 1320

gaagcttcac tgcacagagt ccttggatct tggacgggag attcggttaa ctatgcagca 1380

tctcgatttt tcggtttcga ccagatcgga tgtacctata gtattcggtt tcgaggagtt 1440

agtatcaccg tttctggagg gtcgcgaact cttcagcatc tctgtgagat ggcaattcgg 1500

tctaagcaag aactgctaca gcttgcccca atcgaagtgg aaagtaatgt atcaagagga 1560

tgccctgaag gtactcaaac cttcgaaaaa gaaagcgagt aagttaaaat gcttcttcgt 1620

ctcctattta taatatggtt tgttattgtt aattttgttc ttgtagaaga gcttaattaa 1680

tcgttgttgt tatgaaatac tatttgtatg agatgaactg gtgtaatgta attcatttac 1740

ataagtggag tcagaatcag aatgtttcct ccataactaa ctagacatga agacctgccg 1800

cgtacaattg tcttatattt gaacaactaa aattgaacat cttttgccac aactttataa 1860

gtggttaata tagctcaaat atatggtcaa gttcaataga ttaataatgg aaatatcagt 1920

tatcgaaatt cattaacaat caacttaacg ttattaacta ctaattttat atcatcccct 1980

ttgataaatg atagtacacc aattaggaag gagcatgctc gcctaggaga ttgtcgtttc 2040

ccgccttcag tttgcaagct gctctagccg tgtagccaat acgcaaaccg cctctccccg 2100

cgcgttggga attactagcg cgtgtcgaca agcttgcatg ccggtcaaca tggtggagca 2160

cgacacactt gtctactcca aaaatatcaa agatacagtc tcagaagacc aaagggcaat 2220

tgagactttt caacaaaggg taatatccgg aaacctcctc ggattccatt gcccagctat 2280

ctgtcacttt attgtgaaga tagtggaaaa ggaaggtggc tcctacaaat gccatcattg 2340

cgataaagga aaggccatcg ttgaagatgc ctctgccgac agtggtccca aagatggacc 2400

cccacccacg aggagcatcg tggaaaaaga agacgttcca accacgtctt caaagcaagt 2460

ggattgatgt gataacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga 2520

tacagtctca gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa 2580

cctcctcgga ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga 2640

aggtggctcc tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc 2700

tgccgacagt ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga 2760

cgttccaacc acgtcttcaa agcaagtgga ttgatgtgat atctccactg acgtaaggga 2820

tgacgcacaa tcccactatc cttcgcaaga cccttcctct atataaggaa gttcatttca 2880

tttggagagg cacttttcta atcaatcatc aaacagaacg cagaaaattt cctaaaaaca 2940

aaaaaaaggc atacaaatgg cgaaaaacgt tgcgattttc ggcttattgt tttctcttct 3000

tgtgttggtt ccttctcaga tcttcgcgac gtcactcctc agccaaaacg acacccccat 3060

ctgtctatcc actggcccct ggatctgctg cccaaactaa ctccatggtg accctgggat 3120

gcctggtcaa gggctatttc cctgagccag tgacagtgac ctggaactct ggatccctgt 3180

ccagcggtgt gcacaccttc ccagctgtcc tgcagtctga cctctacact ctgagcagct 3240

cagtgactgt cccctccagc acctggccca gcgagaccgt cacctgcaac gttgcccacc 3300

cggccagcag caccaaggtg gacaagaaaa ttgtgcccag ggattgtggt tgtaagcctt 3360

gcatatgtac agtcccagaa gtatcatctg tcttcatctt ccccccaaag cccaaggatg 3420

tgctcaccat tactctgact cctaaggtca cgtgtgttgt ggtagacatc agcaaggatg 3480

atcccgaggt ccagttcagc tggtttgtag atgatgtgga ggtgcacaca gctcagacgc 3540

aaccccggga ggagcagttc aacagcactt tccgctcagt cagtgaactt cccatcatgc 3600

accaggactg gctcaatggc aaggagacgt ccagattttg gcgatctatt caactgtcgc 3660

cagttcattg gtactggtag tctccctggg ggcaatcagt ttctggatgt gctctaatgg 3720

gtctctacag tgtagaatat gtatttaaag gccttagtcg tgtcgttttt caaataatat 3780

aatcctttta gggttttagt tagtttaaat tttctgttgc tcctgtttag caggtcgtgc 3840

cttcagcaag cacacaaaaa cagagtgttt attttaagtt gtttgtttag tgattcaaaa 3900

aaaaaatcgt tcaaacattt ggcaataaag tttcttaaga ttgaatcctg ttgccggtct 3960

tgcgatgatt atcatataat ttctgttgaa ttacgttaag catgtaataa ttaacatgta 4020

atgcatgacg ttatttatga gatgggtttt tatgattaga gtcccgcaat tatacattta 4080

atacgcgata gaaaacaaaa tatagcgcgc aaactaggat aaattatcgc gcgcggtgtc 4140

atctatgtta ctagatctct agagtctcaa gcttggcgcg cccacgtgac tagtggcact 4200

ggccgtcgtt ttacaacgtc gtgactggga aaaccctggc gttacccaac ttaatcgcct 4260

tgcagcacat ccccctttcg ccagctggcg taatagcgaa gaggcccgca ccgatcgccc 4320

ttcccaacag ttgcgcagcc tgaatggcga atgctagagc agcttgagct tggatcagat 4380

tgtcgtttcc cgccttcagt ttaaactatc agtgtttgac aggatatatt ggcgggtaaa 4440

cctaagagaa aagagcgttt a 4461

<210> 34

<211> 5070

<212> DNA

<213> artificial sequence

<220>

<223> construct 8589 from 2X35S prom to NOS term

<400> 34

gtcaacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga tacagtctca 60

gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa cctcctcgga 120

ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga aggtggctcc 180

tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc tgccgacagt 240

ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga cgttccaacc 300

acgtcttcaa agcaagtgga ttgatgtgat aacatggtgg agcacgacac acttgtctac 360

tccaaaaata tcaaagatac agtctcagaa gaccaaaggg caattgagac ttttcaacaa 420

agggtaatat ccggaaacct cctcggattc cattgcccag ctatctgtca ctttattgtg 480

aagatagtgg aaaaggaagg tggctcctac aaatgccatc attgcgataa aggaaaggcc 540

atcgttgaag atgcctctgc cgacagtggt cccaaagatg gacccccacc cacgaggagc 600

atcgtggaaa aagaagacgt tccaaccacg tcttcaaagc aagtggattg atgtgatatc 660

tccactgacg taagggatga cgcacaatcc cactatcctt cgcaagaccc ttcctctata 720

taaggaagtt catttcattt ggagaggcac ttttctaatc aatcatcaaa cagaacgcag 780

aaaatttcct aaaaacaaaa aaaaggcata caaatggcga aaaacgttgc gattttcggc 840

ttattgtttt ctcttcttgt gttggttcct tctcagatct tcgcggtgaa tcttacgacg 900

cgaacacagt taccacccgc atatacaaat agcttcactc ggggtgttta ttaccccgac 960

aaagtgttca ggtcctccgt gctccactca acacaggacc tctttcttcc tttcttttct 1020

aacgtgacat ggtttcatgc cattcatgta tccggcacta acggtactaa gaggttcgat 1080

aatcctgtgc tccctttcaa tgacggcgtt tactttgcaa gcacagagaa gagtaacatc 1140

atccgaggtt ggatctttgg cactaccctc gattcaaaga cgcagagcct cctcattgtg 1200

aacaatgcca ctaacgtggt gatcaaagtt tgcgagtttc agttctgcaa tgaccctttc 1260

ttgggggtgt actatcataa gaacaacaag tcttggatgg aatctgaatt ccgcgtctat 1320

agcagcgcca acaactgcac ctttgaatac gtgtcccagc ccttccttat ggacctggag 1380

ggaaagcagg gaaactttaa gaatctgaga gagttcgtgt ttaaaaatat cgacggctat 1440

tttaagatct attctaagca cacgcctatt aatctcgtgc gcgatcttcc acaaggcttc 1500

agcgccctgg aaccactcgt ggacctccca attggtatca acatcactag atttcagact 1560

ctgcttgccc tccaccgatc ctatctgaca cccggagact cctctagcgg ctggactgcc 1620

ggcgctgccg cttattacgt tggttatctt cagccacgca cgttcctgct gaagtataac 1680

gagaatggta ctattaccga tgccgtggat tgtgcccttg accccctgtc cgaaactaag 1740

tgcacactca agtcattcac tgtggaaaaa ggaatctacc agacaagcaa ttttcgggtc 1800

cagcctactg agagcattgt gcgctttcct aacatcacaa atctttgccc cttcggagag 1860

gttttcaatg ctacacggtt tgcctccgtg tatgcctgga accgcaagag aatttccaat 1920

tgcgtggccg attactccgt gctctacaat agtgcaagct ttagcacctt taagtgctat 1980

ggcgtatccc ctactaagct taacgacttg tgtttcacaa acgtgtatgc cgactccttt 2040

gtgatacggg gcgacgaagt tagacagata gcaccaggac agacgggaaa gatagctgac 2100

tacaactata agcttcctga tgacttcact ggctgcgtta tcgcgtggaa ttctaacaac 2160

ctggactcaa aagtcggcgg caactataac tatctctatc ggctgttccg caagagtaac 2220

cttaagccct ttgagagaga tataagcact gaaatctacc aggctggcag tacgccctgt 2280

aatggcgtgg aaggctttaa ttgttatttt ccactgcaat cctatggttt tcagccaacc 2340

aatggcgtgg gctaccaacc ataccgcgtc gtggtgctct cctttgaact gctccacgct 2400

cccgcgactg tctgcggccc caagaagtcc acgaaccttg tgaagaataa gtgcgttaat 2460

tttaatttca acggcctcac tggaacagga gtgctcactg agagtaacaa gaagttcctg 2520

ccatttcaac aatttggcag agacatagcc gatactactg acgccgttag ggacccccag 2580

accctcgaga ttctcgatat aacgccctgc tccttcggtg gagtttccgt gatcacgcca 2640

ggcaccaata ccagtaacca ggtcgccgtg ctgtatcagg atgtcaactg tactgaggtg 2700

cccgtagcca tccatgcgga tcagctcaca ccaacttgga gggtgtacag caccggctcc 2760

aatgtattcc agactcgggc cggatgcctt attggcgccg aacacgtgaa caatagttac 2820

gaatgcgata ttccaattgg cgccggaatc tgtgctagct accagactca gacgaactcc 2880

ccaggcagcg ccagcagcgt tgccagccag tcaatcatcg cttatacaat gtcacttgga 2940

gccgaaaact ccgtggctta ctcaaacaac agcatcgcca tccccacaaa cttcaccata 3000

tccgtgacaa ctgagattct gccagtgtcc atgactaaga cgtccgtaga ttgcactatg 3060

tacatatgcg gcgacagcac agaatgttct aatctgctgc tgcaatatgg aagcttctgc 3120

actcaactga acagagcgct cacaggcatc gccgtggagc aggataagaa tacccaggag 3180

gtgttcgccc aagttaagca gatctacaag accccaccca taaaggattt cggtggattc 3240

aattttagtc agatactccc agacccatct aagccatcca agaggagctt tatcgaggat 3300

cttttgttta acaaagttac tctggccgac gccggtttca tcaagcagta cggagattgc 3360

ctcggcgaca tcgctgctcg tgacctcatc tgtgcgcaaa agtttaacgg tctgacggtg 3420

ctgcctcccc tccttactga tgaaatgatc gcccagtata ccagcgcact cctcgctggc 3480

accataacat ccggttggac attcggcgct ggtgcagcac tgcagatacc attcgccatg 3540

caaatggcat atcgtttcaa cggtatcggt gtcacacaga atgtcctata tgagaaccag 3600

aagctgatcg caaatcagtt caatagtgcc atcggaaaaa tccaggatag ccttagcagc 3660

acagcctcag cccttggcaa actccaggat gtcgtgaacc agaatgccca ggctctcaat 3720

accctcgtga agcagctctc atctaatttc ggcgcaattt ccagtgtcct caacgacatc 3780

ctcagccgcc tcgacccccc cgaggccgaa gtgcagattg acagactgat tacaggtcga 3840

ctccagagcc tccagactta cgtgactcag cagctgataa gagccgccga gataagggcc 3900

agcgctaacc tggctgccac aaagatgtct gagtgcgtgc tgggccagtc caagagagta 3960

gacttctgtg gcaaaggcta ccatctgatg agcttcccac aatccgcacc tcacggcgta 4020

gtgttcctcc acgtgacata tgtaccggct caggagaaga atttcactac cgctcctgct 4080

atatgccatg atggaaaggc tcacttcccc cgggaggggg tgttcgtgtc caacggcacc 4140

cattggtttg tgactcagcg gaatttctac gaaccccaga tcataaccac tgacaacaca 4200

tttgtgtccg gaaattgtga cgtggtcatt ggaatagtga acaacactgt ttatgatcca 4260

ctgcagccag aacttgacag ctttaaggag gagctcgaca agtacttcaa gaatcatacg 4320

tcaccagatg tggacctcgg agatattagc ggtatcaatg ccagtgttgt caatattcag 4380

aaggaaatag accgccttaa tgaggtcgcc aaaaatctga acgagagcct catcgatctt 4440

caggagctgg gcaaatatga gcagtacatc aagtggcctt ggtatatttg gcttggcttc 4500

atcgccggcc tgatcgccat agtaatggtc acaattatgc tctgctgcat gacctcttgc 4560

tgctcctgtc tgaaaggctg ctgctcttgc ggatcctgct gcaaatttga tgaggatgac 4620

agtgaaccag tcctgaaggg cgtgaagctg cactatactt agaggcctta gtcgtgtcgt 4680

ttttcaaata atataatcct tttagggttt tagttagttt aaattttctg ttgctcctgt 4740

ttagcaggtc gtgccttcag caagcacaca aaaacagagt gtttatttta agttgtttgt 4800

ttagtgattc aaaaaaaaaa tcgttcaaac atttggcaat aaagtttctt aagattgaat 4860

cctgttgccg gtcttgcgat gattatcata taatttctgt tgaattacgt taagcatgta 4920

ataattaaca tgtaatgcat gacgttattt atgagatggg tttttatgat tagagtcccg 4980

caattataca tttaatacgc gatagaaaac aaaatatagc gcgcaaacta ggataaatta 5040

tcgcgcgcgg tgtcatctat gttactagat 5070

<210> 35

<211> 4436

<212> DNA

<213> artificial sequence

<220>

<223> cloning vector 8716 left-to-right T-DNA

<400> 35

tggcaggata tattgtggtg taaacaaatt gacgcttaga caacttaata acacattgcg 60

gacgttttta atgtactgaa ttaacgccga atcccgggct ggtatattta tatgttgtca 120

aataactcaa aaaccataaa agtttaagtt agcaagtgtg tacattttta cttgaacaaa 180

aatattcacc tactactgtt ataaatcatt attaaacatt agagtaaaga aatatggatg 240

ataagaacaa gagtagtgat attttgacaa caattttgtt gcaacatttg agaaaatttt 300

gttgttctct cttttcattg gtcaaaaaca atagagagag aaaaaggaag agggagaata 360

aaaacataat gtgagtatga gagagaaagt tgtacaaaag ttgtaccaaa atagttgtac 420

aaatatcatt gaggaatttg acaaaagcta cacaaataag ggttaattgc tgtaaataaa 480

taaggatgac gcattagaga gatgtaccat tagagaattt ttggcaagtc attaaaaaga 540

aagaataaat tatttttaaa attaaaagtt gagtcatttg attaaacatg tgattattta 600

atgaattgat gaaagagttg gattaaagtt gtattagtaa ttagaatttg gtgtcaaatt 660

taatttgaca tttgatcttt tcctatatat tgccccatag agtcagttaa ctcattttta 720

tatttcatag atcaaataag agaaataacg gtatattaat ccctccaaaa aaaaaaaacg 780

gtatatttac taaaaaatct aagccacgta ggaggataac aggatccccg taggaggata 840

acatccaatc caaccaatca caacaatcct gatgagataa cccactttaa gcccacgcat 900

ctgtggcaca tctacattat ctaaatcaca cattcttcca cacatctgag ccacacaaaa 960

accaatccac atctttatca cccattctat aaaaaatcac actttgtgag tctacacttt 1020

gattcccttc aaacacatac aaagagaaga gactaattaa ttaattaatc atcttgagag 1080

aaaatggaac gagctataca aggaaacgac gctagggaac aagctaacag tgaacgttgg 1140

gatggaggat caggaggtac cacttctccc ttcaaacttc ctgacgaaag tccgagttgg 1200

actgagtggc ggctacataa cgatgagacg aattcgaatc aagataatcc ccttggtttc 1260

aaggaaagct ggggtttcgg gaaagttgta tttaagagat atctcagata cgacaggacg 1320

gaagcttcac tgcacagagt ccttggatct tggacgggag attcggttaa ctatgcagca 1380

tctcgatttt tcggtttcga ccagatcgga tgtacctata gtattcggtt tcgaggagtt 1440

agtatcaccg tttctggagg gtcgcgaact cttcagcatc tctgtgagat ggcaattcgg 1500

tctaagcaag aactgctaca gcttgcccca atcgaagtgg aaagtaatgt atcaagagga 1560

tgccctgaag gtactcaaac cttcgaaaaa gaaagcgagt aagttaaaat gcttcttcgt 1620

ctcctattta taatatggtt tgttattgtt aattttgttc ttgtagaaga gcttaattaa 1680

tcgttgttgt tatgaaatac tatttgtatg agatgaactg gtgtaatgta attcatttac 1740

ataagtggag tcagaatcag aatgtttcct ccataactaa ctagacatga agacctgccg 1800

cgtacaattg tcttatattt gaacaactaa aattgaacat cttttgccac aactttataa 1860

gtggttaata tagctcaaat atatggtcaa gttcaataga ttaataatgg aaatatcagt 1920

tatcgaaatt cattaacaat caacttaacg ttattaacta ctaattttat atcatcccct 1980

ttgataaatg atagtacacc aattaggaag gagcatgctc gcctaggaga ttgtcgtttc 2040

ccgccttcag tttgcaagct gctctagccg tgtagccaat acgcaaaccg cctctccccg 2100

cgcgttggga attactagcg cgtgtcgaca agcttgcatg ccggtcaaca tggtggagca 2160

cgacacactt gtctactcca aaaatatcaa agatacagtc tcagaagacc aaagggcaat 2220

tgagactttt caacaaaggg taatatccgg aaacctcctc ggattccatt gcccagctat 2280

ctgtcacttt attgtgaaga tagtggaaaa ggaaggtggc tcctacaaat gccatcattg 2340

cgataaagga aaggccatcg ttgaagatgc ctctgccgac agtggtccca aagatggacc 2400

cccacccacg aggagcatcg tggaaaaaga agacgttcca accacgtctt caaagcaagt 2460

ggattgatgt gataacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga 2520

tacagtctca gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa 2580

cctcctcgga ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga 2640

aggtggctcc tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc 2700

tgccgacagt ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga 2760

cgttccaacc acgtcttcaa agcaagtgga ttgatgtgat atctccactg acgtaaggga 2820

tgacgcacaa tcccactatc cttcgcaaga cccttcctct atataaggaa gttcatttca 2880

tttggagagg cactccattt gaatctatca aaccaaaaca cattgagcaa aatggcgaaa 2940

aacgttgcga ttttcggctt attgttttct cttcttgtgt tggttccttc tcagatcttc 3000

gcgacgtcac tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc 3060

tgctgcccaa actaactcca tggtgaccct gggatgcctg gtcaagggct atttccctga 3120

gccagtgaca gtgacctgga actctggatc cctgtccagc ggtgtgcaca ccttcccagc 3180

tgtcctgcag tctgacctct acactctgag cagctcagtg actgtcccct ccagcacctg 3240

gcccagcgag accgtcacct gcaacgttgc ccacccggcc agcagcacca aggtggacaa 3300

gaaaattgtg cccagggatt gtggttgtaa gccttgcata tgtacagtcc cagaagtatc 3360

atctgtcttc atcttccccc caaagcccaa ggatgtgctc accattactc tgactcctaa 3420

ggtcacgtgt gttgtggtag acatcagcaa ggatgatccc gaggtccagt tcagctggtt 3480

tgtagatgat gtggaggtgc acacagctca gacgcaaccc cgggaggagc agttcaacag 3540

cactttccgc tcagtcagtg aacttcccat catgcaccag gactggctca atggcaagga 3600

gacgtccaga ttttggcgat ctattcaact gtcgccagtt cattggtact ggtagtctcc 3660

ctgggggcaa tcagtttctg gatgtgctct aatgggtctc tacagtgtag aatatgtatt 3720

taaaggcctt agtcgtgtcg tttttcaaat aatataatcc ttttagggtt ttagttagtt 3780

taaattttct gttgctcctg tttagcaggt cgtgccttca gcaagcacac aaaaacagag 3840

tgtttatttt aagttgtttg tttagtgatt caaaaaaaaa atcgttcaaa catttggcaa 3900

taaagtttct taagattgaa tcctgttgcc ggtcttgcga tgattatcat ataatttctg 3960

ttgaattacg ttaagcatgt aataattaac atgtaatgca tgacgttatt tatgagatgg 4020

gtttttatga ttagagtccc gcaattatac atttaatacg cgatagaaaa caaaatatag 4080

cgcgcaaact aggataaatt atcgcgcgcg gtgtcatcta tgttactaga tctctagagt 4140

ctcaagcttg gcgcgcccac gtgactagtg gcactggccg tcgttttaca acgtcgtgac 4200

tgggaaaacc ctggcgttac ccaacttaat cgccttgcag cacatccccc tttcgccagc 4260

tggcgtaata gcgaagaggc ccgcaccgat cgcccttccc aacagttgcg cagcctgaat 4320

ggcgaatgct agagcagctt gagcttggat cagattgtcg tttcccgcct tcagtttaaa 4380

ctatcagtgt ttgacaggat atattggcgg gtaaacctaa gagaaaagag cgttta 4436

<210> 36

<211> 5045

<212> DNA

<213> artificial sequence

<220>

<223> construct 8591 from 2X35S prom to NOS term

<400> 36

gtcaacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga tacagtctca 60

gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa cctcctcgga 120

ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga aggtggctcc 180

tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc tgccgacagt 240

ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga cgttccaacc 300

acgtcttcaa agcaagtgga ttgatgtgat aacatggtgg agcacgacac acttgtctac 360

tccaaaaata tcaaagatac agtctcagaa gaccaaaggg caattgagac ttttcaacaa 420

agggtaatat ccggaaacct cctcggattc cattgcccag ctatctgtca ctttattgtg 480

aagatagtgg aaaaggaagg tggctcctac aaatgccatc attgcgataa aggaaaggcc 540

atcgttgaag atgcctctgc cgacagtggt cccaaagatg gacccccacc cacgaggagc 600

atcgtggaaa aagaagacgt tccaaccacg tcttcaaagc aagtggattg atgtgatatc 660

tccactgacg taagggatga cgcacaatcc cactatcctt cgcaagaccc ttcctctata 720

taaggaagtt catttcattt ggagaggcac tccatttgaa tctatcaaac caaaacacat 780

tgagcaaaat ggcgaaaaac gttgcgattt tcggcttatt gttttctctt cttgtgttgg 840

ttccttctca gatcttcgcg gtgaatctta cgacgcgaac acagttacca cccgcatata 900

caaatagctt cactcggggt gtttattacc ccgacaaagt gttcaggtcc tccgtgctcc 960

actcaacaca ggacctcttt cttcctttct tttctaacgt gacatggttt catgccattc 1020

atgtatccgg cactaacggt actaagaggt tcgataatcc tgtgctccct ttcaatgacg 1080

gcgtttactt tgcaagcaca gagaagagta acatcatccg aggttggatc tttggcacta 1140

ccctcgattc aaagacgcag agcctcctca ttgtgaacaa tgccactaac gtggtgatca 1200

aagtttgcga gtttcagttc tgcaatgacc ctttcttggg ggtgtactat cataagaaca 1260

acaagtcttg gatggaatct gaattccgcg tctatagcag cgccaacaac tgcacctttg 1320

aatacgtgtc ccagcccttc cttatggacc tggagggaaa gcagggaaac tttaagaatc 1380

tgagagagtt cgtgtttaaa aatatcgacg gctattttaa gatctattct aagcacacgc 1440

ctattaatct cgtgcgcgat cttccacaag gcttcagcgc cctggaacca ctcgtggacc 1500

tcccaattgg tatcaacatc actagatttc agactctgct tgccctccac cgatcctatc 1560

tgacacccgg agactcctct agcggctgga ctgccggcgc tgccgcttat tacgttggtt 1620

atcttcagcc acgcacgttc ctgctgaagt ataacgagaa tggtactatt accgatgccg 1680

tggattgtgc ccttgacccc ctgtccgaaa ctaagtgcac actcaagtca ttcactgtgg 1740

aaaaaggaat ctaccagaca agcaattttc gggtccagcc tactgagagc attgtgcgct 1800

ttcctaacat cacaaatctt tgccccttcg gagaggtttt caatgctaca cggtttgcct 1860

ccgtgtatgc ctggaaccgc aagagaattt ccaattgcgt ggccgattac tccgtgctct 1920

acaatagtgc aagctttagc acctttaagt gctatggcgt atcccctact aagcttaacg 1980

acttgtgttt cacaaacgtg tatgccgact cctttgtgat acggggcgac gaagttagac 2040

agatagcacc aggacagacg ggaaagatag ctgactacaa ctataagctt cctgatgact 2100

tcactggctg cgttatcgcg tggaattcta acaacctgga ctcaaaagtc ggcggcaact 2160

ataactatct ctatcggctg ttccgcaaga gtaaccttaa gccctttgag agagatataa 2220

gcactgaaat ctaccaggct ggcagtacgc cctgtaatgg cgtggaaggc tttaattgtt 2280

attttccact gcaatcctat ggttttcagc caaccaatgg cgtgggctac caaccatacc 2340

gcgtcgtggt gctctccttt gaactgctcc acgctcccgc gactgtctgc ggccccaaga 2400

agtccacgaa ccttgtgaag aataagtgcg ttaattttaa tttcaacggc ctcactggaa 2460

caggagtgct cactgagagt aacaagaagt tcctgccatt tcaacaattt ggcagagaca 2520

tagccgatac tactgacgcc gttagggacc cccagaccct cgagattctc gatataacgc 2580

cctgctcctt cggtggagtt tccgtgatca cgccaggcac caataccagt aaccaggtcg 2640

ccgtgctgta tcaggatgtc aactgtactg aggtgcccgt agccatccat gcggatcagc 2700

tcacaccaac ttggagggtg tacagcaccg gctccaatgt attccagact cgggccggat 2760

gccttattgg cgccgaacac gtgaacaata gttacgaatg cgatattcca attggcgccg 2820

gaatctgtgc tagctaccag actcagacga actccccagg cagcgccagc agcgttgcca 2880

gccagtcaat catcgcttat acaatgtcac ttggagccga aaactccgtg gcttactcaa 2940

acaacagcat cgccatcccc acaaacttca ccatatccgt gacaactgag attctgccag 3000

tgtccatgac taagacgtcc gtagattgca ctatgtacat atgcggcgac agcacagaat 3060

gttctaatct gctgctgcaa tatggaagct tctgcactca actgaacaga gcgctcacag 3120

gcatcgccgt ggagcaggat aagaataccc aggaggtgtt cgcccaagtt aagcagatct 3180

acaagacccc acccataaag gatttcggtg gattcaattt tagtcagata ctcccagacc 3240

catctaagcc atccaagagg agctttatcg aggatctttt gtttaacaaa gttactctgg 3300

ccgacgccgg tttcatcaag cagtacggag attgcctcgg cgacatcgct gctcgtgacc 3360

tcatctgtgc gcaaaagttt aacggtctga cggtgctgcc tcccctcctt actgatgaaa 3420

tgatcgccca gtataccagc gcactcctcg ctggcaccat aacatccggt tggacattcg 3480

gcgctggtgc agcactgcag ataccattcg ccatgcaaat ggcatatcgt ttcaacggta 3540

tcggtgtcac acagaatgtc ctatatgaga accagaagct gatcgcaaat cagttcaata 3600

gtgccatcgg aaaaatccag gatagcctta gcagcacagc ctcagccctt ggcaaactcc 3660

aggatgtcgt gaaccagaat gcccaggctc tcaataccct cgtgaagcag ctctcatcta 3720

atttcggcgc aatttccagt gtcctcaacg acatcctcag ccgcctcgac ccccccgagg 3780

ccgaagtgca gattgacaga ctgattacag gtcgactcca gagcctccag acttacgtga 3840

ctcagcagct gataagagcc gccgagataa gggccagcgc taacctggct gccacaaaga 3900

tgtctgagtg cgtgctgggc cagtccaaga gagtagactt ctgtggcaaa ggctaccatc 3960

tgatgagctt cccacaatcc gcacctcacg gcgtagtgtt cctccacgtg acatatgtac 4020

cggctcagga gaagaatttc actaccgctc ctgctatatg ccatgatgga aaggctcact 4080

tcccccggga gggggtgttc gtgtccaacg gcacccattg gtttgtgact cagcggaatt 4140

tctacgaacc ccagatcata accactgaca acacatttgt gtccggaaat tgtgacgtgg 4200

tcattggaat agtgaacaac actgtttatg atccactgca gccagaactt gacagcttta 4260

aggaggagct cgacaagtac ttcaagaatc atacgtcacc agatgtggac ctcggagata 4320

ttagcggtat caatgccagt gttgtcaata ttcagaagga aatagaccgc cttaatgagg 4380

tcgccaaaaa tctgaacgag agcctcatcg atcttcagga gctgggcaaa tatgagcagt 4440

acatcaagtg gccttggtat atttggcttg gcttcatcgc cggcctgatc gccatagtaa 4500

tggtcacaat tatgctctgc tgcatgacct cttgctgctc ctgtctgaaa ggctgctgct 4560

cttgcggatc ctgctgcaaa tttgatgagg atgacagtga accagtcctg aagggcgtga 4620

agctgcacta tacttagagg ccttagtcgt gtcgtttttc aaataatata atccttttag 4680

ggttttagtt agtttaaatt ttctgttgct cctgtttagc aggtcgtgcc ttcagcaagc 4740

acacaaaaac agagtgttta ttttaagttg tttgtttagt gattcaaaaa aaaaatcgtt 4800

caaacatttg gcaataaagt ttcttaagat tgaatcctgt tgccggtctt gcgatgatta 4860

tcatataatt tctgttgaat tacgttaagc atgtaataat taacatgtaa tgcatgacgt 4920

tatttatgag atgggttttt atgattagag tcccgcaatt atacatttaa tacgcgatag 4980

aaaacaaaat atagcgcgca aactaggata aattatcgcg cgcggtgtca tctatgttac 5040

tagat 5045

<210> 37

<211> 39

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2S protein, having H5i hemagglutinin CT, C-terminal region of Change 2

<400> 37

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly Ser

20 25 30

Leu Gln Cys Arg Ile Cys Ile

35

<210> 38

<211> 36

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2S protein, having H5i hemagglutinin CT, C-terminal region of variation 3

<400> 38

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Cys Cys Met Cys Ser Asn Gly Ser Leu Gln Cys

20 25 30

Arg Ile Cys Ile

35

<210> 39

<211> 34

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-2S protein, having H5i hemagglutinin CT, C-terminal region of variation 4

<400> 39

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Cys Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

20 25 30

Cys Ile

<210> 40

<211> 151

<212> DNA

<213> Arracacha Virus B

<400> 40

tagtcgtgtc gtttttcaaa taatataatc cttttagggt tttagttagt ttaaattttc 60

tgttgctcct gtttagcagg tcgtgccttc agcaagcaca caaaaacaga gtgtttattt 120

taagttgttt gtttagtgat tcaaaaaaaa a 151

<210> 41

<211> 182

<212> DNA

<213> beet necrotic yellow vein virus

<400> 41

cctatcttga tgaaggttgt tgtggttttc tcattactgt tttattattg tttgagttgc 60

ttatgtcggt tcttgattat gtggtgcata attattgaac taattgtttg ttgggttgta 120

atgtactgac tgggtgtgaa ttgtaccagt cgttaaaggg tttactatca gtatattgat 180

at 182

<210> 42

<211> 132

<212> DNA

<213> southern Bean mosaic Virus

<400> 42

tgaggagttg tataataata cctgcaccct tctctttggc agggagggtg tttcgttttc 60

acaatgccac gcgcttgagg gagaatgcac gttaatcatc cctccgctag tgatggagcg 120

taatccaaaa gt 132

<210> 43

<211> 282

<212> DNA

<213> turnip round-spot virus

<400> 43

tgatttataa tagccataga ttaagtttaa atgtattacg tttgtatttt attctctttt 60

ttaagtttcc tatgttgttt taaattaaat atctgtataa ttagtagatg taaatctgct 120

ttgtgcgttt gacagtctgt ggaaacgcac tggttcatga gataggacca cctaggaggt 180

aggactctgg gttttaatta tctcatttct tagttatacc gtattatata tatgatttag 240

tagtaattgt tttctcttga tatgtattat tactttttta tt 282

<210> 44

<211> 165

<212> DNA

<213> cowpea mosaic Virus

<400> 44

attttcttta gtttgaattt actgttattc ggtgtgcatt tctatgtttg gtgagcggtt 60

ttctgtgctc agagtgtgtt tattttatgt aatttaattt ctttgtgagc tcctgtttag 120

caggtcgtcc cttcagcaag gacacaaaaa gattttaatt ttatt 165

<210> 45

<211> 275

<212> DNA

<213> broad Bean true mosaic Virus

<400> 45

tagttttctt ccgcttttct tttgtagtgt gtggttttct ttgtttcttc ttttcttttc 60

tctttccttt tctcttactc ctgcctggca ggtcgtgcct tcagtaagca caacaaaaat 120

atgcatttat tagagtattt ctttcttctt tagcataaag gtattgaaga cctataaact 180

tcgtccgggt tggggaaagt accagcttag catatcttta gaaaactata tagagctctt 240

taccttgagt tgtttcctaa agtttatgca aaaaa 275

<210> 46

<211> 147

<212> DNA

<213> European melon Virus

<400> 46

ctcacgtctg gggtgagccc tagccaaata ggaaaacgat aagcgctttg catgcaaaat 60

gagttgggcc acaagtgcca ctcgcagcga aggcggtctg aggtttcccc ctggcggtta 120

cttccatatc tttgggagat aactggg 147

<210> 47

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT AA

<400> 47

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 48

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+4P, having H5i hemagglutinin CT AA

<400> 48

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 49

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+6P, having H5i hemagglutinin CT AA

<400> 49

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Pro Ala Leu Gln Ile Pro Phe Pro Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 50

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP+923, having H5i hemagglutinin CT AA

<400> 50

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Phe Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 51

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+4P+923, having H5i hemagglutinin CT AA

<400> 51

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Phe Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 52

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+6P+923, having H5i hemagglutinin CT AA

<400> 52

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Pro Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Pro Ala Leu Gln Ile Pro Phe Pro Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Phe Ser Ser Thr Pro Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 53

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, with H1 Cal hemagglutinin CT AA

<400> 53

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Ser Phe Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 54

<211> 1258

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H3 Minn hemagglutinin CT AA

<400> 54

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Met Trp Ala Cys Gln

1235 1240 1245

Lys Gly Asn Ile Arg Cys Asn Ile Cys Ile

1250 1255

<210> 55

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H6 HK hemagglutinin CT AA

<400> 55

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Gly Leu Trp Met Cys

1235 1240 1245

Ser Asn Gly Ser Met Gln Cys Arg Ile Cys Ile

1250 1255

<210> 56

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H7 Guangdong hemagglutinin CT AA

<400> 56

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Val Phe Ile Cys Val

1235 1240 1245

Lys Asn Gly Asn Met Arg Cys Thr Ile Cys Ile

1250 1255

<210> 57

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H9 HK hemagglutinin CT AA

<400> 57

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Leu Phe Trp Ala Met

1235 1240 1245

Ser Asn Gly Ser Cys Arg Cys Asn Ile Cys Ile

1250 1255

<210> 58

<211> 1259

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, with B/Wash hemagglutinin CT AA

<400> 58

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Val Val Tyr Met Val

1235 1240 1245

Ser Arg Asp Asn Val Ser Cys Ser Ile Cys Leu

1250 1255

<210> 59

<211> 1262

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT (alternative 1) AA

<400> 59

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Met Ala Gly Leu Ser Leu

1235 1240 1245

Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255 1260

<210> 60

<211> 1261

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT (alternative 2) AA

<400> 60

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Ala Gly Leu Ser Leu Trp

1235 1240 1245

Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255 1260

<210> 61

<211> 1258

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT (alternative 3) AA

<400> 61

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Cys Ser

1235 1240 1245

Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 62

<211> 1256

<212> PRT

<213> artificial sequence

<220>

<223> (PDI) modified SARS-CoV-2S protein GSAS+PP, having H5i hemagglutinin CT (alternative 4) AA

<400> 62

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Asn Leu Thr Thr Arg Thr Gln

20 25 30

Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro

35 40 45

Asp Lys Val Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe

50 55 60

Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser

65 70 75 80

Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn

85 90 95

Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly

100 105 110

Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile

115 120 125

Val Asn Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe

130 135 140

Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser

145 150 155 160

Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr

165 170 175

Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln

180 185 190

Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly

195 200 205

Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp

210 215 220

Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile

225 230 235 240

Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser

245 250 255

Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala

260 265 270

Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr

275 280 285

Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro

290 295 300

Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly

305 310 315 320

Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val

325 330 335

Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn

340 345 350

Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser

355 360 365

Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser

370 375 380

Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys

385 390 395 400

Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val

405 410 415

Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr

420 425 430

Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn

435 440 445

Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu

450 455 460

Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu

465 470 475 480

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn

485 490 495

Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val

500 505 510

Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His

515 520 525

Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys

530 535 540

Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val

545 550 555 560

Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg

565 570 575

Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu

580 585 590

Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr

595 600 605

Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val

610 615 620

Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro

625 630 635 640

Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala

645 650 655

Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp

660 665 670

Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn

675 680 685

Ser Pro Gly Ser Ala Ser Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr

690 695 700

Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser

705 710 715 720

Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu

725 730 735

Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys

740 745 750

Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe

755 760 765

Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp

770 775 780

Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr

785 790 795 800

Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

805 810 815

Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

820 825 830

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp

835 840 845

Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

850 855 860

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala

865 870 875 880

Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr

885 890 895

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

900 905 910

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

915 920 925

Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln

930 935 940

Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val

945 950 955 960

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

965 970 975

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

980 985 990

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

995 1000 1005

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

1010 1015 1020

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1025 1030 1035 1040

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1045 1050 1055

His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu

1060 1065 1070

His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro

1075 1080 1085

Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe

1090 1095 1100

Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu

1105 1110 1115 1120

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1125 1130 1135

Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1140 1145 1150

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1155 1160 1165

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1170 1175 1180

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1185 1190 1195 1200

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1205 1210 1215

Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly

1220 1225 1230

Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Ser Asn Gly

1235 1240 1245

Ser Leu Gln Cys Arg Ile Cys Ile

1250 1255

<210> 63

<211> 31

<212> PRT

<213> SARS-CoV-2

<400> 63

Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val

1 5 10 15

Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser

20 25 30

<210> 64

<211> 33

<212> PRT

<213> artificial sequence

<220>

<223> modified TMCT has the intermediate peptide sequence (X) n

<220>

<221> MISC_FEATURE

<222> (21)..(21)

<223> Xaa can be any combination of 0 to 10 amino acids

<220>

<221> misc_feature

<222> (27)..(28)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (30)..(30)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (21)..(21)

<223> The 'Xaa' at location 21 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (27)..(27)

<223> The 'Xaa' at location 27 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (28)..(28)

<223> The 'Xaa' at location 28 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (30)..(30)

<223> The 'Xaa' at location 30 stands for Gln, Arg, Pro, or Leu.

<400> 64

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Xaa Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile Cys

20 25 30

Ile

<210> 65

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S protein GSAS+4P-DNA

<400> 65

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagccccat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca ccctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 66

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S protein GSAS+6P-DNA

<400> 66

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagccccat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

cccgcactgc agataccatt ccccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca ccctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 67

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S protein GSAS+2P+L92DF-DNA

<400> 67

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagctt cagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 68

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S protein GSAS+4P+L92DF-DNA

<400> 68

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagccccat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagctt cagcagcaca ccctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 69

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S protein GSAS+6P+L92DF-DNA

<400> 69

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagccccat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

cccgcactgc agataccatt ccccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagctt cagcagcaca ccctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttaa 3780

<210> 70

<211> 3789

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified S protein with H5i hemagglutinin CT (V1) DNA

<400> 70

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgatgg ccggcctctc tttatggatg tgctccaatg gatcgttaca atgcagaatt 3780

tgcatttaa 3789

<210> 71

<211> 3786

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified S protein with H5i hemagglutinin CT (V2) DNA

<400> 71

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatggccg gcctctcttt atggatgtgc tccaatggat cgttacaatg cagaatttgc 3780

atttaa 3786

<210> 72

<211> 3777

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified S protein with H5i hemagglutinin CT (V3) DNA

<400> 72

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct gctgcatgtg ctccaatgga tcgttacaat gcagaatttg catttaa 3777

<210> 73

<211> 3771

<212> DNA

<213> artificial sequence

<220>

<223> PDI-modified S protein with H5i hemagglutinin CT (V4) DNA

<400> 73

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctct gctgctccaa tggatcgtta caatgcagaa tttgcattta a 3771

<210> 74

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+H2CalDNA

<400> 74

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctca gcttctggat gtgctctaat gggtctctac agtgtagaat atgtatttaa 3780

<210> 75

<211> 3777

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+H2MinnDNA

<400> 75

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctca tgtgggcctg tcagaagggc aacatcagat gcaacatctg catctaa 3777

<210> 76

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+H2HKDNA

<400> 76

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctcg gtctttggat gtgttcaaat ggttcaatgc agtgcaggat atgtatataa 3780

<210> 77

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+H27 Guangdong DNA

<400> 77

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctcg tcttcatatg tgtgaagaat ggaaacatgc ggtgcactat ttgtatataa 3780

<210> 78

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+H2HK DNA

<400> 78

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctcc tgttctgggc catgtccaat ggatcttgca gatgcaacat ttgtatataa 3780

<210> 79

<211> 3780

<212> DNA

<213> artificial sequence

<220>

<223> PDI-S-protein+B/Wash DNA

<400> 79

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgaatct tacgacgcga acacagttac cacccgcata tacaaatagc 120

ttcactcggg gtgtttatta ccccgacaaa gtgttcaggt cctccgtgct ccactcaaca 180

caggacctct ttcttccttt cttttctaac gtgacatggt ttcatgccat tcatgtatcc 240

ggcactaacg gtactaagag gttcgataat cctgtgctcc ctttcaatga cggcgtttac 300

tttgcaagca cagagaagag taacatcatc cgaggttgga tctttggcac taccctcgat 360

tcaaagacgc agagcctcct cattgtgaac aatgccacta acgtggtgat caaagtttgc 420

gagtttcagt tctgcaatga ccctttcttg ggggtgtact atcataagaa caacaagtct 480

tggatggaat ctgaattccg cgtctatagc agcgccaaca actgcacctt tgaatacgtg 540

tcccagccct tccttatgga cctggaggga aagcagggaa actttaagaa tctgagagag 600

ttcgtgttta aaaatatcga cggctatttt aagatctatt ctaagcacac gcctattaat 660

ctcgtgcgcg atcttccaca aggcttcagc gccctggaac cactcgtgga cctcccaatt 720

ggtatcaaca tcactagatt tcagactctg cttgccctcc accgatccta tctgacaccc 780

ggagactcct ctagcggctg gactgccggc gctgccgctt attacgttgg ttatcttcag 840

ccacgcacgt tcctgctgaa gtataacgag aatggtacta ttaccgatgc cgtggattgt 900

gcccttgacc ccctgtccga aactaagtgc acactcaagt cattcactgt ggaaaaagga 960

atctaccaga caagcaattt tcgggtccag cctactgaga gcattgtgcg ctttcctaac 1020

atcacaaatc tttgcccctt cggagaggtt ttcaatgcta cacggtttgc ctccgtgtat 1080

gcctggaacc gcaagagaat ttccaattgc gtggccgatt actccgtgct ctacaatagt 1140

gcaagcttta gcacctttaa gtgctatggc gtatccccta ctaagcttaa cgacttgtgt 1200

ttcacaaacg tgtatgccga ctcctttgtg atacggggcg acgaagttag acagatagca 1260

ccaggacaga cgggaaagat agctgactac aactataagc ttcctgatga cttcactggc 1320

tgcgttatcg cgtggaattc taacaacctg gactcaaaag tcggcggcaa ctataactat 1380

ctctatcggc tgttccgcaa gagtaacctt aagccctttg agagagatat aagcactgaa 1440

atctaccagg ctggcagtac gccctgtaat ggcgtggaag gctttaattg ttattttcca 1500

ctgcaatcct atggttttca gccaaccaat ggcgtgggct accaaccata ccgcgtcgtg 1560

gtgctctcct ttgaactgct ccacgctccc gcgactgtct gcggccccaa gaagtccacg 1620

aaccttgtga agaataagtg cgttaatttt aatttcaacg gcctcactgg aacaggagtg 1680

ctcactgaga gtaacaagaa gttcctgcca tttcaacaat ttggcagaga catagccgat 1740

actactgacg ccgttaggga cccccagacc ctcgagattc tcgatataac gccctgctcc 1800

ttcggtggag tttccgtgat cacgccaggc accaatacca gtaaccaggt cgccgtgctg 1860

tatcaggatg tcaactgtac tgaggtgccc gtagccatcc atgcggatca gctcacacca 1920

acttggaggg tgtacagcac cggctccaat gtattccaga ctcgggccgg atgccttatt 1980

ggcgccgaac acgtgaacaa tagttacgaa tgcgatattc caattggcgc cggaatctgt 2040

gctagctacc agactcagac gaactcccca ggcagcgcca gcagcgttgc cagccagtca 2100

atcatcgctt atacaatgtc acttggagcc gaaaactccg tggcttactc aaacaacagc 2160

atcgccatcc ccacaaactt caccatatcc gtgacaactg agattctgcc agtgtccatg 2220

actaagacgt ccgtagattg cactatgtac atatgcggcg acagcacaga atgttctaat 2280

ctgctgctgc aatatggaag cttctgcact caactgaaca gagcgctcac aggcatcgcc 2340

gtggagcagg ataagaatac ccaggaggtg ttcgcccaag ttaagcagat ctacaagacc 2400

ccacccataa aggatttcgg tggattcaat tttagtcaga tactcccaga cccatctaag 2460

ccatccaaga ggagctttat cgaggatctt ttgtttaaca aagttactct ggccgacgcc 2520

ggtttcatca agcagtacgg agattgcctc ggcgacatcg ctgctcgtga cctcatctgt 2580

gcgcaaaagt ttaacggtct gacggtgctg cctcccctcc ttactgatga aatgatcgcc 2640

cagtatacca gcgcactcct cgctggcacc ataacatccg gttggacatt cggcgctggt 2700

gcagcactgc agataccatt cgccatgcaa atggcatatc gtttcaacgg tatcggtgtc 2760

acacagaatg tcctatatga gaaccagaag ctgatcgcaa atcagttcaa tagtgccatc 2820

ggaaaaatcc aggatagcct tagcagcaca gcctcagccc ttggcaaact ccaggatgtc 2880

gtgaaccaga atgcccaggc tctcaatacc ctcgtgaagc agctctcatc taatttcggc 2940

gcaatttcca gtgtcctcaa cgacatcctc agccgcctcg acccccccga ggccgaagtg 3000

cagattgaca gactgattac aggtcgactc cagagcctcc agacttacgt gactcagcag 3060

ctgataagag ccgccgagat aagggccagc gctaacctgg ctgccacaaa gatgtctgag 3120

tgcgtgctgg gccagtccaa gagagtagac ttctgtggca aaggctacca tctgatgagc 3180

ttcccacaat ccgcacctca cggcgtagtg ttcctccacg tgacatatgt accggctcag 3240

gagaagaatt tcactaccgc tcctgctata tgccatgatg gaaaggctca cttcccccgg 3300

gagggggtgt tcgtgtccaa cggcacccat tggtttgtga ctcagcggaa tttctacgaa 3360

ccccagatca taaccactga caacacattt gtgtccggaa attgtgacgt ggtcattgga 3420

atagtgaaca acactgttta tgatccactg cagccagaac ttgacagctt taaggaggag 3480

ctcgacaagt acttcaagaa tcatacgtca ccagatgtgg acctcggaga tattagcggt 3540

atcaatgcca gtgttgtcaa tattcagaag gaaatagacc gccttaatga ggtcgccaaa 3600

aatctgaacg agagcctcat cgatcttcag gagctgggca aatatgagca gtacatcaag 3660

tggccttggt atatttggct tggcttcatc gccggcctga tcgccatagt aatggtcaca 3720

attatgctcg ttgtttatat ggtctccaga gacaatgttt cttgctccat ttgtctataa 3780

<210> 80

<211> 48

<212> DNA

<213> artificial sequence

<220>

<223> IF-H1HawaiiCT.r

<400> 80

acgacacgac taaggccttt aaatacatat tctacactgt agagaccc 48

<210> 81

<211> 54

<212> DNA

<213> artificial sequence

<220>

<223> IF-H3MinnesotaCT.r

<400> 81

acgacacgac taaggccttt agatgcagat gttgcatctg atgttgccct tctg 54

<210> 82

<211> 52

<212> DNA

<213> artificial sequence

<220>

<223> IF-HongKongCT.r

<400> 82

acgacacgac taaggccttt atatacatat cctgcactgc attgaaccat tt 52

<210> 83

<211> 49

<212> DNA

<213> artificial sequence

<220>

<223> IF-GuangdongCT.r

<400> 83

acgacacgac taaggccttt atatacaaat agtgcaccgc atgtttcca 49

<210> 84

<211> 50

<212> DNA

<213> artificial sequence

<220>

<223> IF-H9HKCT.r

<400> 84

acgacacgac taaggccttt atatacaaat gttgcatctg caagatccat 50

<210> 85

<211> 50

<212> DNA

<213> artificial sequence

<220>

<223> IF-BWashCT.r

<400> 85

acgacacgac taaggccttt atagacaaat ggagcaagaa acattgtctc 50

<210> 86

<211> 50

<212> DNA

<213> artificial sequence

<220>

<223> IF(nbHEL40)-PDI.c

<400> 86

ccaaaacaca ttgagcaaaa tggcgaaaaa cgttgcgatt ttcggcttat 50

<210> 87

<211> 50

<212> DNA

<213> artificial sequence

<220>

<223> IF(AvB+wtCT).r

<400> 87

acgacacgac taaggccttt aggtataatg gagtttcacc cccttcagaa 50

<210> 88

<211> 3801

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 wtTMCT-DNA

<400> 88

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtccgatct ggatcggtgc actacatttg acgatgtgca ggcacctaat 120

tatactcagc acacctcttc catgcggggc gtgtactacc ccgacgagat ttttagaagt 180

gacacactgt acctgaccca agaccttttt ctcccatttt atagcaatgt cacgggattc 240

cacactatca atcacacatt cggaaaccct gttatcccct ttaaagacgg tatctacttt 300

gctgctactg agaaatcgaa tgttgttcgc ggttgggtgt tcggctcaac catgaacaac 360

aagagtcagt cagtaataat tataaacaac tcaaccaatg tcgtcatcag ggcttgcaac 420

ttcgagctct gcgataaccc cttctttgcg gtgtccaaac cgatgggcac tcagacccat 480

accatgattt ttgacaatgc ctttaattgt actttcgaat acatcagcga tgccttctcg 540

ctggatgtgt ccgagaagag cggtaacttc aagcatttgc gggagttcgt tttcaaaaac 600

aaagacgggt ttttgtatgt ctacaaaggc tatcagccca ttgatgtggt cagggatctg 660

cccagtggtt tcaacacact gaagcccatc ttcaagttgc cactcggcat caacatcact 720

aatttccgcg ccatcctaac tgctttttcg ccagcgcagg atatttgggg gacatccgcc 780

gcagcttact tcgtgggata tctgaagccc accactttta tgctaaagta cgacgagaat 840

ggcaccatca ccgatgccgt ggactgctca cagaatcctc tcgcagagct caagtgttca 900

gtgaagtcat ttgagatcga caaagggatc taccaaacat ctaactttcg cgtcgtgcct 960

tccggtgacg tagtccgttt cccaaatatc actaacttgt gcccttttgg tgaagtattc 1020

aacgcaacca aattccccag tgtgtatgcg tgggagcgca aaaagatcag taactgtgtg 1080

gctgactata gtgttctgta caatagcacc ttcttcagca ccttcaagtg ttatggagtg 1140

agcgctacaa aactgaacga tctttgtttc tcaaacgtgt acgccgattc atttgtcgtt 1200

aaaggtgacg atgtgaggca gatcgctcca ggccagacag gtgtgattgc tgactataat 1260

tacaaactgc cagacgactt catggggtgc gtgctagctt ggaatacaag aaacattgac 1320

gccacctcca cgggaaatta caattacaag tatcgttacc ttcgccatgg aaagttgaga 1380

cccttcgagc gtgatataag taacgtgccc tttagtccag atggaaaacc ctgcacaccc 1440

cctgctctca attgctattg gcctctcaat gactacggct tttacacaac tactggcatc 1500

ggataccagc cttaccgggt cgtggtgctc agttttgagt tgcttaacgc acccgccacc 1560

gtgtgtggtc ctaaactttc tactgacctg attaaaaacc aatgcgtcaa cttcaatttt 1620

aacgggctga ccggcaccgg tgtcctgacc cctagctcta agagattcca gccttttcag 1680

cagttcggga gggatgtgag cgactttacc gactctgtca gggatccaaa gaccagcgag 1740

atactggata tctcgccctg cagtttcggt ggcgtgtccg ttattacacc tggcaccaac 1800

gcctcctcag aggtggcggt gctctatcaa gatgtcaact gcactgatgt gtcaactgcc 1860

atccatgccg atcagctgac ccccgcctgg cgcatctaca gtaccgggaa caacgttttt 1920

cagacccagg ccggctgtct aatcggcgca gagcacgttg acacatccta cgaatgtgac 1980

atacctatcg gggcaggcat ttgcgctagc taccataccg tgtcactgtt ggcttccacg 2040

tcacaaaagt caatcgttgc ctacacgatg agtctggggg ctgactcatc tatcgcctac 2100

agcaacaata ccattgcaat tcccacaaac ttcagtatct ccatcacaac agaggtgatg 2160

cccgtttcta tggctaaaac atcagtcgat tgcaatatgt atatatgcgg cgatagtact 2220

gagtgcgcca atctcttgtt acagtacggc tccttttgta cccagctgaa ccgagcactg 2280

tctggaatcg ccgcagaaca ggatcgcaat acccgggaag tcttcgccca ggtgaagcag 2340

atgtacaaaa cgcccactct caagtatttc ggcggattca acttttctca gattttgcct 2400

gacccgctca agccaacaaa acgatctttt atcgaagacc ttctgtttaa caaggtcaca 2460

ctggcggatg ctgggttcat gaaacagtac ggtgaatgcc tgggggacat caatgccaga 2520

gatctgatct gcgcccagaa attcaatggc ttaacagtcc tcccacctct cttgaccgac 2580

gatatgatcg ctgcgtacac cgctgctctg gtatcgggca ccgcgactgc tggctggacc 2640

tttggtgccg gagccgcact ccagatccca ttcgccatgc agatggccta ccgcttcaac 2700

ggaatcgggg tcacccagaa cgtgctgtat gagaaccaga aacagatcgc caatcagttc 2760

aataaggcaa ttagtcagat tcaggagagt cttaccacta ccagcaccgc cctgggcaag 2820

ctgcaagatg ttgtgaacca gaatgcgcag gcattaaaca ctctggttaa acagctgagc 2880

tcaaattttg gtgcaatctc ttcagttctg aacgatatcc tgagtcggct ggatccgcca 2940

gaggctgaag tgcaaattga tcgtttgatc accgggaggc tacaatctct gcagacgtac 3000

gtgacccagc agctcatccg ggcagccgaa attcgcgcat cagccaacct cgctgcaact 3060

aagatgtctg agtgcgtgct gggccagagt aagagggtgg acttttgtgg taagggatac 3120

cacctcatgt cctttccgca agcggctccc cacggcgtgg ttttcttaca cgttacctat 3180

gtgccatccc aagaacgcaa tttcaccacc gctccagcta tctgtcatga gggcaaagca 3240

tatttcccca gggaaggagt atttgtgttt aatggcacgt cctggtttat aacccaacgt 3300

aactttttct ccccacagat tatcacaacc gacaacacat tcgtgtctgg gaattgtgac 3360

gtcgtgatcg ggatcattaa caataccgtt tacgatccct tgcagcccga gcttgactcc 3420

tttaaagagg aactagacaa atactttaag aatcacacct caccggacgt agatttggga 3480

gacatctctg gaattaatgc ctctgtggtg aatatccaga aggagatcga ccgcctgaat 3540

gaagtcgcca agaacctcaa cgagtccctg atagatctgc aagaactggg caaatatgaa 3600

cagtacatca aatggccgtg gtacgtgtgg ttgggcttta tcgctggact tattgcaatc 3660

gtgatggtga cgattctgct ctgctgtatg acttcctgct gctcttgtct gaagggcgcc 3720

tgtagctgtg gttcctgctg caagttcgac gaagacgact ccgaaccagt tctgaagggg 3780

gtgaaactcc attataccta a 3801

<210> 89

<211> 3741

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iTMCT-DNA

<400> 89

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtccgatct ggatcggtgc actacatttg acgatgtgca ggcacctaat 120

tatactcagc acacctcttc catgcggggc gtgtactacc ccgacgagat ttttagaagt 180

gacacactgt acctgaccca agaccttttt ctcccatttt atagcaatgt cacgggattc 240

cacactatca atcacacatt cggaaaccct gttatcccct ttaaagacgg tatctacttt 300

gctgctactg agaaatcgaa tgttgttcgc ggttgggtgt tcggctcaac catgaacaac 360

aagagtcagt cagtaataat tataaacaac tcaaccaatg tcgtcatcag ggcttgcaac 420

ttcgagctct gcgataaccc cttctttgcg gtgtccaaac cgatgggcac tcagacccat 480

accatgattt ttgacaatgc ctttaattgt actttcgaat acatcagcga tgccttctcg 540

ctggatgtgt ccgagaagag cggtaacttc aagcatttgc gggagttcgt tttcaaaaac 600

aaagacgggt ttttgtatgt ctacaaaggc tatcagccca ttgatgtggt cagggatctg 660

cccagtggtt tcaacacact gaagcccatc ttcaagttgc cactcggcat caacatcact 720

aatttccgcg ccatcctaac tgctttttcg ccagcgcagg atatttgggg gacatccgcc 780

gcagcttact tcgtgggata tctgaagccc accactttta tgctaaagta cgacgagaat 840

ggcaccatca ccgatgccgt ggactgctca cagaatcctc tcgcagagct caagtgttca 900

gtgaagtcat ttgagatcga caaagggatc taccaaacat ctaactttcg cgtcgtgcct 960

tccggtgacg tagtccgttt cccaaatatc actaacttgt gcccttttgg tgaagtattc 1020

aacgcaacca aattccccag tgtgtatgcg tgggagcgca aaaagatcag taactgtgtg 1080

gctgactata gtgttctgta caatagcacc ttcttcagca ccttcaagtg ttatggagtg 1140

agcgctacaa aactgaacga tctttgtttc tcaaacgtgt acgccgattc atttgtcgtt 1200

aaaggtgacg atgtgaggca gatcgctcca ggccagacag gtgtgattgc tgactataat 1260

tacaaactgc cagacgactt catggggtgc gtgctagctt ggaatacaag aaacattgac 1320

gccacctcca cgggaaatta caattacaag tatcgttacc ttcgccatgg aaagttgaga 1380

cccttcgagc gtgatataag taacgtgccc tttagtccag atggaaaacc ctgcacaccc 1440

cctgctctca attgctattg gcctctcaat gactacggct tttacacaac tactggcatc 1500

ggataccagc cttaccgggt cgtggtgctc agttttgagt tgcttaacgc acccgccacc 1560

gtgtgtggtc ctaaactttc tactgacctg attaaaaacc aatgcgtcaa cttcaatttt 1620

aacgggctga ccggcaccgg tgtcctgacc cctagctcta agagattcca gccttttcag 1680

cagttcggga gggatgtgag cgactttacc gactctgtca gggatccaaa gaccagcgag 1740

atactggata tctcgccctg cagtttcggt ggcgtgtccg ttattacacc tggcaccaac 1800

gcctcctcag aggtggcggt gctctatcaa gatgtcaact gcactgatgt gtcaactgcc 1860

atccatgccg atcagctgac ccccgcctgg cgcatctaca gtaccgggaa caacgttttt 1920

cagacccagg ccggctgtct aatcggcgca gagcacgttg acacatccta cgaatgtgac 1980

atacctatcg gggcaggcat ttgcgctagc taccataccg tgtcactgtt ggcttccacg 2040

tcacaaaagt caatcgttgc ctacacgatg agtctggggg ctgactcatc tatcgcctac 2100

agcaacaata ccattgcaat tcccacaaac ttcagtatct ccatcacaac agaggtgatg 2160

cccgtttcta tggctaaaac atcagtcgat tgcaatatgt atatatgcgg cgatagtact 2220

gagtgcgcca atctcttgtt acagtacggc tccttttgta cccagctgaa ccgagcactg 2280

tctggaatcg ccgcagaaca ggatcgcaat acccgggaag tcttcgccca ggtgaagcag 2340

atgtacaaaa cgcccactct caagtatttc ggcggattca acttttctca gattttgcct 2400

gacccgctca agccaacaaa acgatctttt atcgaagacc ttctgtttaa caaggtcaca 2460

ctggcggatg ctgggttcat gaaacagtac ggtgaatgcc tgggggacat caatgccaga 2520

gatctgatct gcgcccagaa attcaatggc ttaacagtcc tcccacctct cttgaccgac 2580

gatatgatcg ctgcgtacac cgctgctctg gtatcgggca ccgcgactgc tggctggacc 2640

tttggtgccg gagccgcact ccagatccca ttcgccatgc agatggccta ccgcttcaac 2700

ggaatcgggg tcacccagaa cgtgctgtat gagaaccaga aacagatcgc caatcagttc 2760

aataaggcaa ttagtcagat tcaggagagt cttaccacta ccagcaccgc cctgggcaag 2820

ctgcaagatg ttgtgaacca gaatgcgcag gcattaaaca ctctggttaa acagctgagc 2880

tcaaattttg gtgcaatctc ttcagttctg aacgatatcc tgagtcggct ggatccgcca 2940

gaggctgaag tgcaaattga tcgtttgatc accgggaggc tacaatctct gcagacgtac 3000

gtgacccagc agctcatccg ggcagccgaa attcgcgcat cagccaacct cgctgcaact 3060

aagatgtctg agtgcgtgct gggccagagt aagagggtgg acttttgtgg taagggatac 3120

cacctcatgt cctttccgca agcggctccc cacggcgtgg ttttcttaca cgttacctat 3180

gtgccatccc aagaacgcaa tttcaccacc gctccagcta tctgtcatga gggcaaagca 3240

tatttcccca gggaaggagt atttgtgttt aatggcacgt cctggtttat aacccaacgt 3300

aactttttct ccccacagat tatcacaacc gacaacacat tcgtgtctgg gaattgtgac 3360

gtcgtgatcg ggatcattaa caataccgtt tacgatccct tgcagcccga gcttgactcc 3420

tttaaagagg aactagacaa atactttaag aatcacacct caccggacgt agatttggga 3480

gacatctctg gaattaatgc ctctgtggtg aatatccaga aggagatcga ccgcctgaat 3540

gaagtcgcca agaacctcaa cgagtccctg atagatctgc aagaactggg caaatatgaa 3600

cagtacatca aatggccgtg gtaccaaata ctgtcaattt attcaacagt ggcgagttcc 3660

ctagcactgg caatcatgat ggctggtcta tctttatgga tgtgctccaa tggatcgtta 3720

caatgcagaa tttgcattta a 3741

<210> 90

<211> 3732

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iCT-DNA

<400> 90

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtccgatct ggatcggtgc actacatttg acgatgtgca ggcacctaat 120

tatactcagc acacctcttc catgcggggc gtgtactacc ccgacgagat ttttagaagt 180

gacacactgt acctgaccca agaccttttt ctcccatttt atagcaatgt cacgggattc 240

cacactatca atcacacatt cggaaaccct gttatcccct ttaaagacgg tatctacttt 300

gctgctactg agaaatcgaa tgttgttcgc ggttgggtgt tcggctcaac catgaacaac 360

aagagtcagt cagtaataat tataaacaac tcaaccaatg tcgtcatcag ggcttgcaac 420

ttcgagctct gcgataaccc cttctttgcg gtgtccaaac cgatgggcac tcagacccat 480

accatgattt ttgacaatgc ctttaattgt actttcgaat acatcagcga tgccttctcg 540

ctggatgtgt ccgagaagag cggtaacttc aagcatttgc gggagttcgt tttcaaaaac 600

aaagacgggt ttttgtatgt ctacaaaggc tatcagccca ttgatgtggt cagggatctg 660

cccagtggtt tcaacacact gaagcccatc ttcaagttgc cactcggcat caacatcact 720

aatttccgcg ccatcctaac tgctttttcg ccagcgcagg atatttgggg gacatccgcc 780

gcagcttact tcgtgggata tctgaagccc accactttta tgctaaagta cgacgagaat 840

ggcaccatca ccgatgccgt ggactgctca cagaatcctc tcgcagagct caagtgttca 900

gtgaagtcat ttgagatcga caaagggatc taccaaacat ctaactttcg cgtcgtgcct 960

tccggtgacg tagtccgttt cccaaatatc actaacttgt gcccttttgg tgaagtattc 1020

aacgcaacca aattccccag tgtgtatgcg tgggagcgca aaaagatcag taactgtgtg 1080

gctgactata gtgttctgta caatagcacc ttcttcagca ccttcaagtg ttatggagtg 1140

agcgctacaa aactgaacga tctttgtttc tcaaacgtgt acgccgattc atttgtcgtt 1200

aaaggtgacg atgtgaggca gatcgctcca ggccagacag gtgtgattgc tgactataat 1260

tacaaactgc cagacgactt catggggtgc gtgctagctt ggaatacaag aaacattgac 1320

gccacctcca cgggaaatta caattacaag tatcgttacc ttcgccatgg aaagttgaga 1380

cccttcgagc gtgatataag taacgtgccc tttagtccag atggaaaacc ctgcacaccc 1440

cctgctctca attgctattg gcctctcaat gactacggct tttacacaac tactggcatc 1500

ggataccagc cttaccgggt cgtggtgctc agttttgagt tgcttaacgc acccgccacc 1560

gtgtgtggtc ctaaactttc tactgacctg attaaaaacc aatgcgtcaa cttcaatttt 1620

aacgggctga ccggcaccgg tgtcctgacc cctagctcta agagattcca gccttttcag 1680

cagttcggga gggatgtgag cgactttacc gactctgtca gggatccaaa gaccagcgag 1740

atactggata tctcgccctg cagtttcggt ggcgtgtccg ttattacacc tggcaccaac 1800

gcctcctcag aggtggcggt gctctatcaa gatgtcaact gcactgatgt gtcaactgcc 1860

atccatgccg atcagctgac ccccgcctgg cgcatctaca gtaccgggaa caacgttttt 1920

cagacccagg ccggctgtct aatcggcgca gagcacgttg acacatccta cgaatgtgac 1980

atacctatcg gggcaggcat ttgcgctagc taccataccg tgtcactgtt ggcttccacg 2040

tcacaaaagt caatcgttgc ctacacgatg agtctggggg ctgactcatc tatcgcctac 2100

agcaacaata ccattgcaat tcccacaaac ttcagtatct ccatcacaac agaggtgatg 2160

cccgtttcta tggctaaaac atcagtcgat tgcaatatgt atatatgcgg cgatagtact 2220

gagtgcgcca atctcttgtt acagtacggc tccttttgta cccagctgaa ccgagcactg 2280

tctggaatcg ccgcagaaca ggatcgcaat acccgggaag tcttcgccca ggtgaagcag 2340

atgtacaaaa cgcccactct caagtatttc ggcggattca acttttctca gattttgcct 2400

gacccgctca agccaacaaa acgatctttt atcgaagacc ttctgtttaa caaggtcaca 2460

ctggcggatg ctgggttcat gaaacagtac ggtgaatgcc tgggggacat caatgccaga 2520

gatctgatct gcgcccagaa attcaatggc ttaacagtcc tcccacctct cttgaccgac 2580

gatatgatcg ctgcgtacac cgctgctctg gtatcgggca ccgcgactgc tggctggacc 2640

tttggtgccg gagccgcact ccagatccca ttcgccatgc agatggccta ccgcttcaac 2700

ggaatcgggg tcacccagaa cgtgctgtat gagaaccaga aacagatcgc caatcagttc 2760

aataaggcaa ttagtcagat tcaggagagt cttaccacta ccagcaccgc cctgggcaag 2820

ctgcaagatg ttgtgaacca gaatgcgcag gcattaaaca ctctggttaa acagctgagc 2880

tcaaattttg gtgcaatctc ttcagttctg aacgatatcc tgagtcggct ggatccgcca 2940

gaggctgaag tgcaaattga tcgtttgatc accgggaggc tacaatctct gcagacgtac 3000

gtgacccagc agctcatccg ggcagccgaa attcgcgcat cagccaacct cgctgcaact 3060

aagatgtctg agtgcgtgct gggccagagt aagagggtgg acttttgtgg taagggatac 3120

cacctcatgt cctttccgca agcggctccc cacggcgtgg ttttcttaca cgttacctat 3180

gtgccatccc aagaacgcaa tttcaccacc gctccagcta tctgtcatga gggcaaagca 3240

tatttcccca gggaaggagt atttgtgttt aatggcacgt cctggtttat aacccaacgt 3300

aactttttct ccccacagat tatcacaacc gacaacacat tcgtgtctgg gaattgtgac 3360

gtcgtgatcg ggatcattaa caataccgtt tacgatccct tgcagcccga gcttgactcc 3420

tttaaagagg aactagacaa atactttaag aatcacacct caccggacgt agatttggga 3480

gacatctctg gaattaatgc ctctgtggtg aatatccaga aggagatcga ccgcctgaat 3540

gaagtcgcca agaacctcaa cgagtccctg atagatctgc aagaactggg caaatatgaa 3600

cagtacatca aatggccgtg gtacgtgtgg ttgggcttta tcgctggact tattgcaatc 3660

gtgatggtga cgattctgct ctctttatgg atgtgctcca atggatcgtt acaatgcaga 3720

atttgcattt aa 3732

<210> 91

<211> 3723

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iCT(V4)-DNA

<400> 91

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtccgatct ggatcggtgc actacatttg acgatgtgca ggcacctaat 120

tatactcagc acacctcttc catgcggggc gtgtactacc ccgacgagat ttttagaagt 180

gacacactgt acctgaccca agaccttttt ctcccatttt atagcaatgt cacgggattc 240

cacactatca atcacacatt cggaaaccct gttatcccct ttaaagacgg tatctacttt 300

gctgctactg agaaatcgaa tgttgttcgc ggttgggtgt tcggctcaac catgaacaac 360

aagagtcagt cagtaataat tataaacaac tcaaccaatg tcgtcatcag ggcttgcaac 420

ttcgagctct gcgataaccc cttctttgcg gtgtccaaac cgatgggcac tcagacccat 480

accatgattt ttgacaatgc ctttaattgt actttcgaat acatcagcga tgccttctcg 540

ctggatgtgt ccgagaagag cggtaacttc aagcatttgc gggagttcgt tttcaaaaac 600

aaagacgggt ttttgtatgt ctacaaaggc tatcagccca ttgatgtggt cagggatctg 660

cccagtggtt tcaacacact gaagcccatc ttcaagttgc cactcggcat caacatcact 720

aatttccgcg ccatcctaac tgctttttcg ccagcgcagg atatttgggg gacatccgcc 780

gcagcttact tcgtgggata tctgaagccc accactttta tgctaaagta cgacgagaat 840

ggcaccatca ccgatgccgt ggactgctca cagaatcctc tcgcagagct caagtgttca 900

gtgaagtcat ttgagatcga caaagggatc taccaaacat ctaactttcg cgtcgtgcct 960

tccggtgacg tagtccgttt cccaaatatc actaacttgt gcccttttgg tgaagtattc 1020

aacgcaacca aattccccag tgtgtatgcg tgggagcgca aaaagatcag taactgtgtg 1080

gctgactata gtgttctgta caatagcacc ttcttcagca ccttcaagtg ttatggagtg 1140

agcgctacaa aactgaacga tctttgtttc tcaaacgtgt acgccgattc atttgtcgtt 1200

aaaggtgacg atgtgaggca gatcgctcca ggccagacag gtgtgattgc tgactataat 1260

tacaaactgc cagacgactt catggggtgc gtgctagctt ggaatacaag aaacattgac 1320

gccacctcca cgggaaatta caattacaag tatcgttacc ttcgccatgg aaagttgaga 1380

cccttcgagc gtgatataag taacgtgccc tttagtccag atggaaaacc ctgcacaccc 1440

cctgctctca attgctattg gcctctcaat gactacggct tttacacaac tactggcatc 1500

ggataccagc cttaccgggt cgtggtgctc agttttgagt tgcttaacgc acccgccacc 1560

gtgtgtggtc ctaaactttc tactgacctg attaaaaacc aatgcgtcaa cttcaatttt 1620

aacgggctga ccggcaccgg tgtcctgacc cctagctcta agagattcca gccttttcag 1680

cagttcggga gggatgtgag cgactttacc gactctgtca gggatccaaa gaccagcgag 1740

atactggata tctcgccctg cagtttcggt ggcgtgtccg ttattacacc tggcaccaac 1800

gcctcctcag aggtggcggt gctctatcaa gatgtcaact gcactgatgt gtcaactgcc 1860

atccatgccg atcagctgac ccccgcctgg cgcatctaca gtaccgggaa caacgttttt 1920

cagacccagg ccggctgtct aatcggcgca gagcacgttg acacatccta cgaatgtgac 1980

atacctatcg gggcaggcat ttgcgctagc taccataccg tgtcactgtt ggcttccacg 2040

tcacaaaagt caatcgttgc ctacacgatg agtctggggg ctgactcatc tatcgcctac 2100

agcaacaata ccattgcaat tcccacaaac ttcagtatct ccatcacaac agaggtgatg 2160

cccgtttcta tggctaaaac atcagtcgat tgcaatatgt atatatgcgg cgatagtact 2220

gagtgcgcca atctcttgtt acagtacggc tccttttgta cccagctgaa ccgagcactg 2280

tctggaatcg ccgcagaaca ggatcgcaat acccgggaag tcttcgccca ggtgaagcag 2340

atgtacaaaa cgcccactct caagtatttc ggcggattca acttttctca gattttgcct 2400

gacccgctca agccaacaaa acgatctttt atcgaagacc ttctgtttaa caaggtcaca 2460

ctggcggatg ctgggttcat gaaacagtac ggtgaatgcc tgggggacat caatgccaga 2520

gatctgatct gcgcccagaa attcaatggc ttaacagtcc tcccacctct cttgaccgac 2580

gatatgatcg ctgcgtacac cgctgctctg gtatcgggca ccgcgactgc tggctggacc 2640

tttggtgccg gagccgcact ccagatccca ttcgccatgc agatggccta ccgcttcaac 2700

ggaatcgggg tcacccagaa cgtgctgtat gagaaccaga aacagatcgc caatcagttc 2760

aataaggcaa ttagtcagat tcaggagagt cttaccacta ccagcaccgc cctgggcaag 2820

ctgcaagatg ttgtgaacca gaatgcgcag gcattaaaca ctctggttaa acagctgagc 2880

tcaaattttg gtgcaatctc ttcagttctg aacgatatcc tgagtcggct ggatccgcca 2940

gaggctgaag tgcaaattga tcgtttgatc accgggaggc tacaatctct gcagacgtac 3000

gtgacccagc agctcatccg ggcagccgaa attcgcgcat cagccaacct cgctgcaact 3060

aagatgtctg agtgcgtgct gggccagagt aagagggtgg acttttgtgg taagggatac 3120

cacctcatgt cctttccgca agcggctccc cacggcgtgg ttttcttaca cgttacctat 3180

gtgccatccc aagaacgcaa tttcaccacc gctccagcta tctgtcatga gggcaaagca 3240

tatttcccca gggaaggagt atttgtgttt aatggcacgt cctggtttat aacccaacgt 3300

aactttttct ccccacagat tatcacaacc gacaacacat tcgtgtctgg gaattgtgac 3360

gtcgtgatcg ggatcattaa caataccgtt tacgatccct tgcagcccga gcttgactcc 3420

tttaaagagg aactagacaa atactttaag aatcacacct caccggacgt agatttggga 3480

gacatctctg gaattaatgc ctctgtggtg aatatccaga aggagatcga ccgcctgaat 3540

gaagtcgcca agaacctcaa cgagtccctg atagatctgc aagaactggg caaatatgaa 3600

cagtacatca aatggccgtg gtacgtgtgg ttgggcttta tcgctggact tattgcaatc 3660

gtgatggtga cgattctgct ctgctgctcc aatggatcgt tacaatgcag aatttgcatt 3720

taa 3723

<210> 92

<211> 3732

<212> DNA

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H1cCT-DNA

<400> 92

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtccgatct ggatcggtgc actacatttg acgatgtgca ggcacctaat 120

tatactcagc acacctcttc catgcggggc gtgtactacc ccgacgagat ttttagaagt 180

gacacactgt acctgaccca agaccttttt ctcccatttt atagcaatgt cacgggattc 240

cacactatca atcacacatt cggaaaccct gttatcccct ttaaagacgg tatctacttt 300

gctgctactg agaaatcgaa tgttgttcgc ggttgggtgt tcggctcaac catgaacaac 360

aagagtcagt cagtaataat tataaacaac tcaaccaatg tcgtcatcag ggcttgcaac 420

ttcgagctct gcgataaccc cttctttgcg gtgtccaaac cgatgggcac tcagacccat 480

accatgattt ttgacaatgc ctttaattgt actttcgaat acatcagcga tgccttctcg 540

ctggatgtgt ccgagaagag cggtaacttc aagcatttgc gggagttcgt tttcaaaaac 600

aaagacgggt ttttgtatgt ctacaaaggc tatcagccca ttgatgtggt cagggatctg 660

cccagtggtt tcaacacact gaagcccatc ttcaagttgc cactcggcat caacatcact 720

aatttccgcg ccatcctaac tgctttttcg ccagcgcagg atatttgggg gacatccgcc 780

gcagcttact tcgtgggata tctgaagccc accactttta tgctaaagta cgacgagaat 840

ggcaccatca ccgatgccgt ggactgctca cagaatcctc tcgcagagct caagtgttca 900

gtgaagtcat ttgagatcga caaagggatc taccaaacat ctaactttcg cgtcgtgcct 960

tccggtgacg tagtccgttt cccaaatatc actaacttgt gcccttttgg tgaagtattc 1020

aacgcaacca aattccccag tgtgtatgcg tgggagcgca aaaagatcag taactgtgtg 1080

gctgactata gtgttctgta caatagcacc ttcttcagca ccttcaagtg ttatggagtg 1140

agcgctacaa aactgaacga tctttgtttc tcaaacgtgt acgccgattc atttgtcgtt 1200

aaaggtgacg atgtgaggca gatcgctcca ggccagacag gtgtgattgc tgactataat 1260

tacaaactgc cagacgactt catggggtgc gtgctagctt ggaatacaag aaacattgac 1320

gccacctcca cgggaaatta caattacaag tatcgttacc ttcgccatgg aaagttgaga 1380

cccttcgagc gtgatataag taacgtgccc tttagtccag atggaaaacc ctgcacaccc 1440

cctgctctca attgctattg gcctctcaat gactacggct tttacacaac tactggcatc 1500

ggataccagc cttaccgggt cgtggtgctc agttttgagt tgcttaacgc acccgccacc 1560

gtgtgtggtc ctaaactttc tactgacctg attaaaaacc aatgcgtcaa cttcaatttt 1620

aacgggctga ccggcaccgg tgtcctgacc cctagctcta agagattcca gccttttcag 1680

cagttcggga gggatgtgag cgactttacc gactctgtca gggatccaaa gaccagcgag 1740

atactggata tctcgccctg cagtttcggt ggcgtgtccg ttattacacc tggcaccaac 1800

gcctcctcag aggtggcggt gctctatcaa gatgtcaact gcactgatgt gtcaactgcc 1860

atccatgccg atcagctgac ccccgcctgg cgcatctaca gtaccgggaa caacgttttt 1920

cagacccagg ccggctgtct aatcggcgca gagcacgttg acacatccta cgaatgtgac 1980

atacctatcg gggcaggcat ttgcgctagc taccataccg tgtcactgtt ggcttccacg 2040

tcacaaaagt caatcgttgc ctacacgatg agtctggggg ctgactcatc tatcgcctac 2100

agcaacaata ccattgcaat tcccacaaac ttcagtatct ccatcacaac agaggtgatg 2160

cccgtttcta tggctaaaac atcagtcgat tgcaatatgt atatatgcgg cgatagtact 2220

gagtgcgcca atctcttgtt acagtacggc tccttttgta cccagctgaa ccgagcactg 2280

tctggaatcg ccgcagaaca ggatcgcaat acccgggaag tcttcgccca ggtgaagcag 2340

atgtacaaaa cgcccactct caagtatttc ggcggattca acttttctca gattttgcct 2400

gacccgctca agccaacaaa acgatctttt atcgaagacc ttctgtttaa caaggtcaca 2460

ctggcggatg ctgggttcat gaaacagtac ggtgaatgcc tgggggacat caatgccaga 2520

gatctgatct gcgcccagaa attcaatggc ttaacagtcc tcccacctct cttgaccgac 2580

gatatgatcg ctgcgtacac cgctgctctg gtatcgggca ccgcgactgc tggctggacc 2640

tttggtgccg gagccgcact ccagatccca ttcgccatgc agatggccta ccgcttcaac 2700

ggaatcgggg tcacccagaa cgtgctgtat gagaaccaga aacagatcgc caatcagttc 2760

aataaggcaa ttagtcagat tcaggagagt cttaccacta ccagcaccgc cctgggcaag 2820

ctgcaagatg ttgtgaacca gaatgcgcag gcattaaaca ctctggttaa acagctgagc 2880

tcaaattttg gtgcaatctc ttcagttctg aacgatatcc tgagtcggct ggatccgcca 2940

gaggctgaag tgcaaattga tcgtttgatc accgggaggc tacaatctct gcagacgtac 3000

gtgacccagc agctcatccg ggcagccgaa attcgcgcat cagccaacct cgctgcaact 3060

aagatgtctg agtgcgtgct gggccagagt aagagggtgg acttttgtgg taagggatac 3120

cacctcatgt cctttccgca agcggctccc cacggcgtgg ttttcttaca cgttacctat 3180

gtgccatccc aagaacgcaa tttcaccacc gctccagcta tctgtcatga gggcaaagca 3240

tatttcccca gggaaggagt atttgtgttt aatggcacgt cctggtttat aacccaacgt 3300

aactttttct ccccacagat tatcacaacc gacaacacat tcgtgtctgg gaattgtgac 3360

gtcgtgatcg ggatcattaa caataccgtt tacgatccct tgcagcccga gcttgactcc 3420

tttaaagagg aactagacaa atactttaag aatcacacct caccggacgt agatttggga 3480

gacatctctg gaattaatgc ctctgtggtg aatatccaga aggagatcga ccgcctgaat 3540

gaagtcgcca agaacctcaa cgagtccctg atagatctgc aagaactggg caaatatgaa 3600

cagtacatca aatggccgtg gtacgtgtgg ttgggcttta tcgctggact tattgcaatc 3660

gtgatggtga cgattctgct cagcttctgg atgtgctcta atgggtctct acagtgtaga 3720

atatgtattt aa 3732

<210> 93

<211> 1266

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 wtTMCT-AA

<400> 93

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Ser Asp Leu Asp Arg Cys Thr Thr

20 25 30

Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln His Thr Ser Ser Met

35 40 45

Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg Ser Asp Thr Leu Tyr

50 55 60

Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser Asn Val Thr Gly Phe

65 70 75 80

His Thr Ile Asn His Thr Phe Gly Asn Pro Val Ile Pro Phe Lys Asp

85 90 95

Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn Val Val Arg Gly Trp

100 105 110

Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln Ser Val Ile Ile Ile

115 120 125

Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys Asn Phe Glu Leu Cys

130 135 140

Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met Gly Thr Gln Thr His

145 150 155 160

Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr Phe Glu Tyr Ile Ser

165 170 175

Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser Gly Asn Phe Lys His

180 185 190

Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly Phe Leu Tyr Val Tyr

195 200 205

Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp Leu Pro Ser Gly Phe

210 215 220

Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu Gly Ile Asn Ile Thr

225 230 235 240

Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro Ala Gln Asp Ile Trp

245 250 255

Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr Leu Lys Pro Thr Thr

260 265 270

Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys Ser Val Lys Ser Phe

290 295 300

Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Val Pro

305 310 315 320

Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu

340 345 350

Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val

385 390 395 400

Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu

420 425 430

Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn

435 440 445

Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg

450 455 460

Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro

465 470 475 480

Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr

485 490 495

Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys Leu Ser Thr

515 520 525

Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg Phe Gln Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp Ser Val Arg Asp Pro

565 570 575

Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser Glu Val Ala Val Leu

595 600 605

Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr Gly Asn Asn Val Phe

625 630 635 640

Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu His Val Asp Thr Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr His

660 665 670

Thr Val Ser Leu Leu Ala Ser Thr Ser Gln Lys Ser Ile Val Ala Tyr

675 680 685

Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala Tyr Ser Asn Asn Thr

690 695 700

Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile Thr Thr Glu Val Met

705 710 715 720

Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys Asn Met Tyr Ile Cys

725 730 735

Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu Gln Tyr Gly Ser Phe

740 745 750

Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile Ala Ala Glu Gln Asp

755 760 765

Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys Gln Met Tyr Lys Thr

770 775 780

Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

785 790 795 800

Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

805 810 815

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met Lys Gln Tyr Gly Glu

820 825 830

Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

835 840 845

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Asp Met Ile Ala

850 855 860

Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala Thr Ala Gly Trp Thr

865 870 875 880

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

885 890 895

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

900 905 910

Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala Ile Ser Gln Ile Gln

915 920 925

Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly Lys Leu Gln Asp Val

930 935 940

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

945 950 955 960

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

965 970 975

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

980 985 990

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

995 1000 1005

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1010 1015 1020

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1025 1030 1035 1040

His Leu Met Ser Phe Pro Gln Ala Ala Pro His Gly Val Val Phe Leu

1045 1050 1055

His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro

1060 1065 1070

Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe

1075 1080 1085

Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser

1090 1095 1100

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1105 1110 1115 1120

Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1125 1130 1135

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1140 1145 1150

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1155 1160 1165

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1170 1175 1180

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1185 1190 1195 1200

Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly

1205 1210 1215

Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Cys Cys Met Thr Ser

1220 1225 1230

Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser Cys Gly Ser Cys Cys Lys

1235 1240 1245

Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His

1250 1255 1260

Tyr Thr

1265

<210> 94

<211> 1246

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iTMCT-AA

<400> 94

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Ser Asp Leu Asp Arg Cys Thr Thr

20 25 30

Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln His Thr Ser Ser Met

35 40 45

Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg Ser Asp Thr Leu Tyr

50 55 60

Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser Asn Val Thr Gly Phe

65 70 75 80

His Thr Ile Asn His Thr Phe Gly Asn Pro Val Ile Pro Phe Lys Asp

85 90 95

Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn Val Val Arg Gly Trp

100 105 110

Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln Ser Val Ile Ile Ile

115 120 125

Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys Asn Phe Glu Leu Cys

130 135 140

Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met Gly Thr Gln Thr His

145 150 155 160

Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr Phe Glu Tyr Ile Ser

165 170 175

Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser Gly Asn Phe Lys His

180 185 190

Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly Phe Leu Tyr Val Tyr

195 200 205

Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp Leu Pro Ser Gly Phe

210 215 220

Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu Gly Ile Asn Ile Thr

225 230 235 240

Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro Ala Gln Asp Ile Trp

245 250 255

Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr Leu Lys Pro Thr Thr

260 265 270

Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys Ser Val Lys Ser Phe

290 295 300

Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Val Pro

305 310 315 320

Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu

340 345 350

Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val

385 390 395 400

Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu

420 425 430

Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn

435 440 445

Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg

450 455 460

Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro

465 470 475 480

Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr

485 490 495

Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys Leu Ser Thr

515 520 525

Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg Phe Gln Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp Ser Val Arg Asp Pro

565 570 575

Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser Glu Val Ala Val Leu

595 600 605

Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr Gly Asn Asn Val Phe

625 630 635 640

Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu His Val Asp Thr Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr His

660 665 670

Thr Val Ser Leu Leu Ala Ser Thr Ser Gln Lys Ser Ile Val Ala Tyr

675 680 685

Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala Tyr Ser Asn Asn Thr

690 695 700

Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile Thr Thr Glu Val Met

705 710 715 720

Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys Asn Met Tyr Ile Cys

725 730 735

Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu Gln Tyr Gly Ser Phe

740 745 750

Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile Ala Ala Glu Gln Asp

755 760 765

Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys Gln Met Tyr Lys Thr

770 775 780

Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

785 790 795 800

Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

805 810 815

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met Lys Gln Tyr Gly Glu

820 825 830

Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

835 840 845

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Asp Met Ile Ala

850 855 860

Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala Thr Ala Gly Trp Thr

865 870 875 880

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

885 890 895

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

900 905 910

Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala Ile Ser Gln Ile Gln

915 920 925

Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly Lys Leu Gln Asp Val

930 935 940

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

945 950 955 960

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

965 970 975

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

980 985 990

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

995 1000 1005

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1010 1015 1020

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1025 1030 1035 1040

His Leu Met Ser Phe Pro Gln Ala Ala Pro His Gly Val Val Phe Leu

1045 1050 1055

His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro

1060 1065 1070

Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe

1075 1080 1085

Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser

1090 1095 1100

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1105 1110 1115 1120

Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1125 1130 1135

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1140 1145 1150

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1155 1160 1165

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1170 1175 1180

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1185 1190 1195 1200

Gln Tyr Ile Lys Trp Pro Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr

1205 1210 1215

Val Ala Ser Ser Leu Ala Leu Ala Ile Met Met Ala Gly Leu Ser Leu

1220 1225 1230

Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1235 1240 1245

<210> 95

<211> 1243

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iCT-AA

<400> 95

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Ser Asp Leu Asp Arg Cys Thr Thr

20 25 30

Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln His Thr Ser Ser Met

35 40 45

Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg Ser Asp Thr Leu Tyr

50 55 60

Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser Asn Val Thr Gly Phe

65 70 75 80

His Thr Ile Asn His Thr Phe Gly Asn Pro Val Ile Pro Phe Lys Asp

85 90 95

Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn Val Val Arg Gly Trp

100 105 110

Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln Ser Val Ile Ile Ile

115 120 125

Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys Asn Phe Glu Leu Cys

130 135 140

Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met Gly Thr Gln Thr His

145 150 155 160

Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr Phe Glu Tyr Ile Ser

165 170 175

Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser Gly Asn Phe Lys His

180 185 190

Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly Phe Leu Tyr Val Tyr

195 200 205

Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp Leu Pro Ser Gly Phe

210 215 220

Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu Gly Ile Asn Ile Thr

225 230 235 240

Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro Ala Gln Asp Ile Trp

245 250 255

Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr Leu Lys Pro Thr Thr

260 265 270

Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys Ser Val Lys Ser Phe

290 295 300

Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Val Pro

305 310 315 320

Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu

340 345 350

Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val

385 390 395 400

Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu

420 425 430

Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn

435 440 445

Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg

450 455 460

Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro

465 470 475 480

Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr

485 490 495

Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys Leu Ser Thr

515 520 525

Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg Phe Gln Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp Ser Val Arg Asp Pro

565 570 575

Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser Glu Val Ala Val Leu

595 600 605

Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr Gly Asn Asn Val Phe

625 630 635 640

Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu His Val Asp Thr Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr His

660 665 670

Thr Val Ser Leu Leu Ala Ser Thr Ser Gln Lys Ser Ile Val Ala Tyr

675 680 685

Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala Tyr Ser Asn Asn Thr

690 695 700

Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile Thr Thr Glu Val Met

705 710 715 720

Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys Asn Met Tyr Ile Cys

725 730 735

Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu Gln Tyr Gly Ser Phe

740 745 750

Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile Ala Ala Glu Gln Asp

755 760 765

Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys Gln Met Tyr Lys Thr

770 775 780

Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

785 790 795 800

Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

805 810 815

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met Lys Gln Tyr Gly Glu

820 825 830

Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

835 840 845

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Asp Met Ile Ala

850 855 860

Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala Thr Ala Gly Trp Thr

865 870 875 880

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

885 890 895

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

900 905 910

Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala Ile Ser Gln Ile Gln

915 920 925

Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly Lys Leu Gln Asp Val

930 935 940

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

945 950 955 960

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

965 970 975

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

980 985 990

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

995 1000 1005

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1010 1015 1020

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1025 1030 1035 1040

His Leu Met Ser Phe Pro Gln Ala Ala Pro His Gly Val Val Phe Leu

1045 1050 1055

His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro

1060 1065 1070

Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe

1075 1080 1085

Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser

1090 1095 1100

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1105 1110 1115 1120

Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1125 1130 1135

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1140 1145 1150

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1155 1160 1165

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1170 1175 1180

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1185 1190 1195 1200

Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly

1205 1210 1215

Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Ser Leu Trp Met Cys

1220 1225 1230

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1235 1240

<210> 96

<211> 1240

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H5iCT(V4)-AA

<400> 96

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Ser Asp Leu Asp Arg Cys Thr Thr

20 25 30

Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln His Thr Ser Ser Met

35 40 45

Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg Ser Asp Thr Leu Tyr

50 55 60

Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser Asn Val Thr Gly Phe

65 70 75 80

His Thr Ile Asn His Thr Phe Gly Asn Pro Val Ile Pro Phe Lys Asp

85 90 95

Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn Val Val Arg Gly Trp

100 105 110

Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln Ser Val Ile Ile Ile

115 120 125

Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys Asn Phe Glu Leu Cys

130 135 140

Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met Gly Thr Gln Thr His

145 150 155 160

Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr Phe Glu Tyr Ile Ser

165 170 175

Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser Gly Asn Phe Lys His

180 185 190

Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly Phe Leu Tyr Val Tyr

195 200 205

Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp Leu Pro Ser Gly Phe

210 215 220

Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu Gly Ile Asn Ile Thr

225 230 235 240

Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro Ala Gln Asp Ile Trp

245 250 255

Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr Leu Lys Pro Thr Thr

260 265 270

Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys Ser Val Lys Ser Phe

290 295 300

Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Val Pro

305 310 315 320

Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu

340 345 350

Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val

385 390 395 400

Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu

420 425 430

Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn

435 440 445

Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg

450 455 460

Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro

465 470 475 480

Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr

485 490 495

Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys Leu Ser Thr

515 520 525

Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg Phe Gln Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp Ser Val Arg Asp Pro

565 570 575

Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser Glu Val Ala Val Leu

595 600 605

Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr Gly Asn Asn Val Phe

625 630 635 640

Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu His Val Asp Thr Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr His

660 665 670

Thr Val Ser Leu Leu Ala Ser Thr Ser Gln Lys Ser Ile Val Ala Tyr

675 680 685

Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala Tyr Ser Asn Asn Thr

690 695 700

Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile Thr Thr Glu Val Met

705 710 715 720

Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys Asn Met Tyr Ile Cys

725 730 735

Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu Gln Tyr Gly Ser Phe

740 745 750

Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile Ala Ala Glu Gln Asp

755 760 765

Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys Gln Met Tyr Lys Thr

770 775 780

Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

785 790 795 800

Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

805 810 815

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met Lys Gln Tyr Gly Glu

820 825 830

Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

835 840 845

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Asp Met Ile Ala

850 855 860

Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala Thr Ala Gly Trp Thr

865 870 875 880

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

885 890 895

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

900 905 910

Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala Ile Ser Gln Ile Gln

915 920 925

Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly Lys Leu Gln Asp Val

930 935 940

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

945 950 955 960

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

965 970 975

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

980 985 990

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

995 1000 1005

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1010 1015 1020

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1025 1030 1035 1040

His Leu Met Ser Phe Pro Gln Ala Ala Pro His Gly Val Val Phe Leu

1045 1050 1055

His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro

1060 1065 1070

Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe

1075 1080 1085

Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser

1090 1095 1100

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1105 1110 1115 1120

Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1125 1130 1135

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1140 1145 1150

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1155 1160 1165

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1170 1175 1180

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1185 1190 1195 1200

Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly

1205 1210 1215

Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Cys Cys Ser Asn Gly

1220 1225 1230

Ser Leu Gln Cys Arg Ile Cys Ile

1235 1240

<210> 97

<211> 1243

<212> PRT

<213> artificial sequence

<220>

<223> PDI-SARS-COV-1 H1cCT-AA

<400> 97

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Ser Asp Leu Asp Arg Cys Thr Thr

20 25 30

Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln His Thr Ser Ser Met

35 40 45

Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg Ser Asp Thr Leu Tyr

50 55 60

Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser Asn Val Thr Gly Phe

65 70 75 80

His Thr Ile Asn His Thr Phe Gly Asn Pro Val Ile Pro Phe Lys Asp

85 90 95

Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn Val Val Arg Gly Trp

100 105 110

Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln Ser Val Ile Ile Ile

115 120 125

Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys Asn Phe Glu Leu Cys

130 135 140

Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met Gly Thr Gln Thr His

145 150 155 160

Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr Phe Glu Tyr Ile Ser

165 170 175

Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser Gly Asn Phe Lys His

180 185 190

Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly Phe Leu Tyr Val Tyr

195 200 205

Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp Leu Pro Ser Gly Phe

210 215 220

Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu Gly Ile Asn Ile Thr

225 230 235 240

Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro Ala Gln Asp Ile Trp

245 250 255

Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr Leu Lys Pro Thr Thr

260 265 270

Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile Thr Asp Ala Val Asp

275 280 285

Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys Ser Val Lys Ser Phe

290 295 300

Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Val Pro

305 310 315 320

Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe

325 330 335

Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser Val Tyr Ala Trp Glu

340 345 350

Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn

355 360 365

Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Ala Thr Lys

370 375 380

Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala Asp Ser Phe Val Val

385 390 395 400

Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Val Ile

405 410 415

Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Met Gly Cys Val Leu

420 425 430

Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser Thr Gly Asn Tyr Asn

435 440 445

Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu Arg Pro Phe Glu Arg

450 455 460

Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly Lys Pro Cys Thr Pro

465 470 475 480

Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp Tyr Gly Phe Tyr Thr

485 490 495

Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe

500 505 510

Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly Pro Lys Leu Ser Thr

515 520 525

Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn Phe Asn Gly Leu Thr

530 535 540

Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg Phe Gln Pro Phe Gln

545 550 555 560

Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp Ser Val Arg Asp Pro

565 570 575

Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys Ser Phe Gly Gly Val

580 585 590

Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser Glu Val Ala Val Leu

595 600 605

Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr Ala Ile His Ala Asp

610 615 620

Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr Gly Asn Asn Val Phe

625 630 635 640

Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu His Val Asp Thr Ser

645 650 655

Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr His

660 665 670

Thr Val Ser Leu Leu Ala Ser Thr Ser Gln Lys Ser Ile Val Ala Tyr

675 680 685

Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala Tyr Ser Asn Asn Thr

690 695 700

Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile Thr Thr Glu Val Met

705 710 715 720

Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys Asn Met Tyr Ile Cys

725 730 735

Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu Gln Tyr Gly Ser Phe

740 745 750

Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile Ala Ala Glu Gln Asp

755 760 765

Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys Gln Met Tyr Lys Thr

770 775 780

Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro

785 790 795 800

Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe

805 810 815

Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met Lys Gln Tyr Gly Glu

820 825 830

Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe

835 840 845

Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Asp Met Ile Ala

850 855 860

Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala Thr Ala Gly Trp Thr

865 870 875 880

Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala

885 890 895

Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn

900 905 910

Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala Ile Ser Gln Ile Gln

915 920 925

Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly Lys Leu Gln Asp Val

930 935 940

Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser

945 950 955 960

Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg

965 970 975

Leu Asp Pro Pro Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly

980 985 990

Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala

995 1000 1005

Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu

1010 1015 1020

Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr

1025 1030 1035 1040

His Leu Met Ser Phe Pro Gln Ala Ala Pro His Gly Val Val Phe Leu

1045 1050 1055

His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn Phe Thr Thr Ala Pro

1060 1065 1070

Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro Arg Glu Gly Val Phe

1075 1080 1085

Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln Arg Asn Phe Phe Ser

1090 1095 1100

Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp

1105 1110 1115 1120

Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro

1125 1130 1135

Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His

1140 1145 1150

Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser

1155 1160 1165

Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys

1170 1175 1180

Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu

1185 1190 1195 1200

Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly

1205 1210 1215

Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu Ser Phe Trp Met Cys

1220 1225 1230

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1235 1240

<210> 98

<211> 60

<212> DNA

<213> artificial sequence

<220>

<223> IF(AvB+wtCT-MERS).r

<400> 98

acgacacgac taaggccttc agtgaacgtg gaccttgtga ggctcaaggt catactcctc 60

<210> 99

<211> 49

<212> DNA

<213> artificial sequence

<220>

<223> IF(H1cCT-wtTM).r

<400> 99

acgacacgac taaggccttc aaatacatat tctacactgt agagaccca 49

<210> 100

<211> 48

<212> DNA

<213> artificial sequence

<220>

<223> IF(H5ITMCT).r

<400> 100

acgacacgac taaggccttc aaatgcaaat tctgcattgt aacgatcc 48

<210> 101

<211> 4083

<212> DNA

<213> artificial sequence

<220>

<223> PDI-MERS-wtTMCT-DNA

<400> 101

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtatgtcga tgtgggtccc gatagtgtta agtccgcctg catcgaagtg 120

gacattcagc agaccttctt cgataagact tggcctcggc caattgatgt gtccaaggcc 180

gacggcatta tctaccccca aggtcggaca tattccaaca taactatcac ctatcagggg 240

ctattccctt atcagggcga ccatggggac atgtacgttt acagcgctgg tcacgctaca 300

gggacgaccc cccagaagct cttcgtggcg aactatagtc aggacgtgaa acagtttgcc 360

aacggttttg tagtgcgcat cggggcagcc gctaactcca ctggtactgt tattatcagc 420

ccttccacga gtgccacaat tcgaaagatc tatccggcct tcatgctagg atcctctgtg 480

ggcaatttta gcgacggtaa gatgggtcgg ttcttcaacc acacgcttgt gctgcttccc 540

gatgggtgcg gtactttgct gagggccttt tactgtatcc tagagccccg atccggcaac 600

cactgccccg ccgggaactc gtatacttcc tttgccactt atcatactcc agccacggat 660

tgtagcgatg ggaactacaa taggaacgcc agtttgaatt cctttaaaga gtacttcaac 720

ttgcggaatt gtaccttcat gtatacatat aacattactg aggacgaaat tctcgaatgg 780

ttcggaatca ctcaaacagc ccagggagtg cacctcttta gttctcgcta tgtggactta 840

tatggaggca atatgtttca attcgccacc ttacccgtct acgatacgat caagtattac 900

tcgatcatac cccactccat taggtccatt cagagcgatc gcaaggcatg ggccgcattc 960

tatgtgtata agctccagcc cctgaccttc ctcttggatt tctccgtgga cggctacatc 1020

agaagggcta tcgattgcgg gttcaacgac ctcagccagc tgcattgttc ttatgagagc 1080

tttgacgtgg aaagcggagt ttactcagtc tcttcctttg aggctaaacc ttcaggtagc 1140

gtcgtagagc aagcagaggg tgtggagtgc gatttctcac cactgctcag cggaacccca 1200

ccccaggtct acaactttaa gcggctcgtg ttcacaaact gtaactataa cttgactaag 1260

ttgctgtcac tcttttccgt gaatgatttt acatgctccc aaatcagccc agccgctatt 1320

gcgtctaatt gctattcctc attgatcctg gattacttca gttaccccct ctctatgaag 1380

agcgatctct cggttagtag cgctgggcct atttcccagt ttaactacaa acaatccttt 1440

tccaatccaa catgcctgat cttagctact gtaccccaca acctgactac tattacgaag 1500

ccactcaagt actcatacat taataagtgc agccgattcc tcagtgatga tcgcaccgaa 1560

gtgccgcagc ttgtaaacgc gaaccagtac tccccatgcg tctctattgt gccttctaca 1620

gtgtgggaag acggcgatta ttatagaaag cagctgtcgc cactggaagg tggcgggtgg 1680

ctagttgcca gtgggtccac agttgccatg accgagcaac ttcagatggg gtttggcata 1740

acagtgcagt atggtaccga tacgaacagc gtgtgtccaa aattggaatt tgctaacgac 1800

accaagatcg cctcccagtt gggaaattgt gttgaatatt ccctgtacgg agtgtcaggc 1860

cggggggtgt tccaaaattg caccgccgtg ggagtgaggc agcaaagatt cgtgtacgac 1920

gcataccaga atctagtcgg atactattct gacgatggaa actactactg tctgcgcgct 1980

tgcgtctcag tgcccgtgag tgtcatatat gataaggaga ccaagactca cgctactctc 2040

tttggttctg tcgcgtgcga acacatttcc tctacaatgt cccagtatag tcgctccact 2100

cggtctatgt taaagcgcag agacagtacc tacggccctc tacagacacc tgtggggtgc 2160

gttctcggcc ttgtcaattc tagcctgttt gtggaggatt gtaagctgcc ccttggtcaa 2220

agcttatgcg cactgcccga tacgcccagc acacttacac cagcttcagt ggggtccgtc 2280

cccggggaaa tgagattggc ctcgatcgct ttcaaccacc ccatacaggt ggatcagctc 2340

aactcgtcat acttcaagct aagcatccct actaatttct cctttggtgt gactcaggag 2400

tacattcaga ccacaattca aaaggtgacc gttgactgca agcagtatgt gtgcaacggg 2460

ttccagaaat gtgaacagct gctccgggag tatggccagt tctgttctaa aatcaaccag 2520

gccctccacg gagcaaacct taggcaggac gattctgtca gaaacctctt tgccagcgtc 2580

aagagttctc agagttcccc tattatacct ggcttcggcg gggatttcaa cctgacacta 2640

cttgaacctg taagcatatc aaccggaagt cgcagtgccc gttccgccat cgaggatctg 2700

ctcttcgaca aagtaactat tgcagatccc ggatacatgc aggggtatga cgactgcatg 2760

cagcagggtc cagcctctgc aagggatctg atatgcgcac agtatgtcgc tgggtacaaa 2820

gtgttgcctc ctctcatgga cgtgaacatg gaagcggcct atacctcctc acttctaggc 2880

tccatagcgg gcgtgggatg gaccgcaggg ctttcaagct tcgccgcaat tccctttgct 2940

caatctatct tctacaggct taatggcgtt ggaatcaccc agcaggtgtt aagcgaaaac 3000

cagaaattga ttgccaataa gtttaaccaa gctttggggg ccatgcagac aggctttaca 3060

accacaaacg aggctttcca taaagtacag gatgcggtaa acaataacgc acaagccctg 3120

tcaaagctgg cttcagagct ctcaaataca tttggcgcta tatccgcgtc tatcggcgat 3180

atcatacaac ggttggaccc acccgaacag gacgcacaga ttgatcgttt gatcaacggg 3240

aggcttacca ccttaaacgc ttttgtggcc cagcaactgg tgcggtctga gagcgccgcc 3300

ttgagcgctc agctggcaaa ggataaagtg aatgaatgcg tgaaagctca atcaaagaga 3360

agtgggtttt gtgggcaggg tactcatatt gtttcctttg tggtgaacgc cccaaatgga 3420

ctctacttta tgcatgttgg atactacccg agcaaccaca tcgaggtcgt ttccgcctat 3480

gggctttgtg acgcagcaaa ccctactaac tgtatcgcgc cagttaatgg ctactttatt 3540

aaaacaaata acacacgcat tgtggatgaa tggagttaca cagggtccag cttctacgct 3600

ccagagccta tcacctctct gaacacaaag tatgtggcac ctcaggtcac atatcagaac 3660

atctcgacaa acctgccccc cccactcttg ggcaactcca cagggatcga cttccaggac 3720

gagcttgacg aattcttcaa gaacgtgtcc accagtatcc ctaattttgg ttcgctgacc 3780

caaattaaca caaccctgct cgatctgaca tatgaaatgc tttcactaca gcaggtggtc 3840

aaagcgttga acgagtcgta tatcgacctg aaagagttag ggaattacac atactataac 3900

aaatggccct ggtatatttg gttaggattc attgccgggc tggtggccct tgccttgtgc 3960

gtatttttca tcttgtgctg taccggttgc ggtacgaatt gcatgggaaa actgaaatgt 4020

aatcggtgct gcgatcgcta tgaggagtat gaccttgagc ctcacaaggt ccacgttcac 4080

tga 4083

<210> 102

<211> 4032

<212> DNA

<213> artificial sequence

<220>

<223> PDI-MERS-H5iTMCT-DNA

<400> 102

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtatgtcga tgtgggtccc gatagtgtta agtccgcctg catcgaagtg 120

gacattcagc agaccttctt cgataagact tggcctcggc caattgatgt gtccaaggcc 180

gacggcatta tctaccccca aggtcggaca tattccaaca taactatcac ctatcagggg 240

ctattccctt atcagggcga ccatggggac atgtacgttt acagcgctgg tcacgctaca 300

gggacgaccc cccagaagct cttcgtggcg aactatagtc aggacgtgaa acagtttgcc 360

aacggttttg tagtgcgcat cggggcagcc gctaactcca ctggtactgt tattatcagc 420

ccttccacga gtgccacaat tcgaaagatc tatccggcct tcatgctagg atcctctgtg 480

ggcaatttta gcgacggtaa gatgggtcgg ttcttcaacc acacgcttgt gctgcttccc 540

gatgggtgcg gtactttgct gagggccttt tactgtatcc tagagccccg atccggcaac 600

cactgccccg ccgggaactc gtatacttcc tttgccactt atcatactcc agccacggat 660

tgtagcgatg ggaactacaa taggaacgcc agtttgaatt cctttaaaga gtacttcaac 720

ttgcggaatt gtaccttcat gtatacatat aacattactg aggacgaaat tctcgaatgg 780

ttcggaatca ctcaaacagc ccagggagtg cacctcttta gttctcgcta tgtggactta 840

tatggaggca atatgtttca attcgccacc ttacccgtct acgatacgat caagtattac 900

tcgatcatac cccactccat taggtccatt cagagcgatc gcaaggcatg ggccgcattc 960

tatgtgtata agctccagcc cctgaccttc ctcttggatt tctccgtgga cggctacatc 1020

agaagggcta tcgattgcgg gttcaacgac ctcagccagc tgcattgttc ttatgagagc 1080

tttgacgtgg aaagcggagt ttactcagtc tcttcctttg aggctaaacc ttcaggtagc 1140

gtcgtagagc aagcagaggg tgtggagtgc gatttctcac cactgctcag cggaacccca 1200

ccccaggtct acaactttaa gcggctcgtg ttcacaaact gtaactataa cttgactaag 1260

ttgctgtcac tcttttccgt gaatgatttt acatgctccc aaatcagccc agccgctatt 1320

gcgtctaatt gctattcctc attgatcctg gattacttca gttaccccct ctctatgaag 1380

agcgatctct cggttagtag cgctgggcct atttcccagt ttaactacaa acaatccttt 1440

tccaatccaa catgcctgat cttagctact gtaccccaca acctgactac tattacgaag 1500

ccactcaagt actcatacat taataagtgc agccgattcc tcagtgatga tcgcaccgaa 1560

gtgccgcagc ttgtaaacgc gaaccagtac tccccatgcg tctctattgt gccttctaca 1620

gtgtgggaag acggcgatta ttatagaaag cagctgtcgc cactggaagg tggcgggtgg 1680

ctagttgcca gtgggtccac agttgccatg accgagcaac ttcagatggg gtttggcata 1740

acagtgcagt atggtaccga tacgaacagc gtgtgtccaa aattggaatt tgctaacgac 1800

accaagatcg cctcccagtt gggaaattgt gttgaatatt ccctgtacgg agtgtcaggc 1860

cggggggtgt tccaaaattg caccgccgtg ggagtgaggc agcaaagatt cgtgtacgac 1920

gcataccaga atctagtcgg atactattct gacgatggaa actactactg tctgcgcgct 1980

tgcgtctcag tgcccgtgag tgtcatatat gataaggaga ccaagactca cgctactctc 2040

tttggttctg tcgcgtgcga acacatttcc tctacaatgt cccagtatag tcgctccact 2100

cggtctatgt taaagcgcag agacagtacc tacggccctc tacagacacc tgtggggtgc 2160

gttctcggcc ttgtcaattc tagcctgttt gtggaggatt gtaagctgcc ccttggtcaa 2220

agcttatgcg cactgcccga tacgcccagc acacttacac cagcttcagt ggggtccgtc 2280

cccggggaaa tgagattggc ctcgatcgct ttcaaccacc ccatacaggt ggatcagctc 2340

aactcgtcat acttcaagct aagcatccct actaatttct cctttggtgt gactcaggag 2400

tacattcaga ccacaattca aaaggtgacc gttgactgca agcagtatgt gtgcaacggg 2460

ttccagaaat gtgaacagct gctccgggag tatggccagt tctgttctaa aatcaaccag 2520

gccctccacg gagcaaacct taggcaggac gattctgtca gaaacctctt tgccagcgtc 2580

aagagttctc agagttcccc tattatacct ggcttcggcg gggatttcaa cctgacacta 2640

cttgaacctg taagcatatc aaccggaagt cgcagtgccc gttccgccat cgaggatctg 2700

ctcttcgaca aagtaactat tgcagatccc ggatacatgc aggggtatga cgactgcatg 2760

cagcagggtc cagcctctgc aagggatctg atatgcgcac agtatgtcgc tgggtacaaa 2820

gtgttgcctc ctctcatgga cgtgaacatg gaagcggcct atacctcctc acttctaggc 2880

tccatagcgg gcgtgggatg gaccgcaggg ctttcaagct tcgccgcaat tccctttgct 2940

caatctatct tctacaggct taatggcgtt ggaatcaccc agcaggtgtt aagcgaaaac 3000

cagaaattga ttgccaataa gtttaaccaa gctttggggg ccatgcagac aggctttaca 3060

accacaaacg aggctttcca taaagtacag gatgcggtaa acaataacgc acaagccctg 3120

tcaaagctgg cttcagagct ctcaaataca tttggcgcta tatccgcgtc tatcggcgat 3180

atcatacaac ggttggaccc acccgaacag gacgcacaga ttgatcgttt gatcaacggg 3240

aggcttacca ccttaaacgc ttttgtggcc cagcaactgg tgcggtctga gagcgccgcc 3300

ttgagcgctc agctggcaaa ggataaagtg aatgaatgcg tgaaagctca atcaaagaga 3360

agtgggtttt gtgggcaggg tactcatatt gtttcctttg tggtgaacgc cccaaatgga 3420

ctctacttta tgcatgttgg atactacccg agcaaccaca tcgaggtcgt ttccgcctat 3480

gggctttgtg acgcagcaaa ccctactaac tgtatcgcgc cagttaatgg ctactttatt 3540

aaaacaaata acacacgcat tgtggatgaa tggagttaca cagggtccag cttctacgct 3600

ccagagccta tcacctctct gaacacaaag tatgtggcac ctcaggtcac atatcagaac 3660

atctcgacaa acctgccccc cccactcttg ggcaactcca cagggatcga cttccaggac 3720

gagcttgacg aattcttcaa gaacgtgtcc accagtatcc ctaattttgg ttcgctgacc 3780

caaattaaca caaccctgct cgatctgaca tatgaaatgc tttcactaca gcaggtggtc 3840

aaagcgttga acgagtcgta tatcgacctg aaagagttag ggaattacac atactataac 3900

aaatggccct ggtatcaaat actgtcaatt tattcaacag tggcgagttc cctagcactg 3960

gcaatcatga tggctggtct atctttatgg atgtgctcca atggatcgtt acaatgcaga 4020

atttgcattt ga 4032

<210> 103

<211> 4026

<212> DNA

<213> artificial sequence

<220>

<223> PDI-MERS-H5iCT-DNA

<400> 103

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtatgtcga tgtgggtccc gatagtgtta agtccgcctg catcgaagtg 120

gacattcagc agaccttctt cgataagact tggcctcggc caattgatgt gtccaaggcc 180

gacggcatta tctaccccca aggtcggaca tattccaaca taactatcac ctatcagggg 240

ctattccctt atcagggcga ccatggggac atgtacgttt acagcgctgg tcacgctaca 300

gggacgaccc cccagaagct cttcgtggcg aactatagtc aggacgtgaa acagtttgcc 360

aacggttttg tagtgcgcat cggggcagcc gctaactcca ctggtactgt tattatcagc 420

ccttccacga gtgccacaat tcgaaagatc tatccggcct tcatgctagg atcctctgtg 480

ggcaatttta gcgacggtaa gatgggtcgg ttcttcaacc acacgcttgt gctgcttccc 540

gatgggtgcg gtactttgct gagggccttt tactgtatcc tagagccccg atccggcaac 600

cactgccccg ccgggaactc gtatacttcc tttgccactt atcatactcc agccacggat 660

tgtagcgatg ggaactacaa taggaacgcc agtttgaatt cctttaaaga gtacttcaac 720

ttgcggaatt gtaccttcat gtatacatat aacattactg aggacgaaat tctcgaatgg 780

ttcggaatca ctcaaacagc ccagggagtg cacctcttta gttctcgcta tgtggactta 840

tatggaggca atatgtttca attcgccacc ttacccgtct acgatacgat caagtattac 900

tcgatcatac cccactccat taggtccatt cagagcgatc gcaaggcatg ggccgcattc 960

tatgtgtata agctccagcc cctgaccttc ctcttggatt tctccgtgga cggctacatc 1020

agaagggcta tcgattgcgg gttcaacgac ctcagccagc tgcattgttc ttatgagagc 1080

tttgacgtgg aaagcggagt ttactcagtc tcttcctttg aggctaaacc ttcaggtagc 1140

gtcgtagagc aagcagaggg tgtggagtgc gatttctcac cactgctcag cggaacccca 1200

ccccaggtct acaactttaa gcggctcgtg ttcacaaact gtaactataa cttgactaag 1260

ttgctgtcac tcttttccgt gaatgatttt acatgctccc aaatcagccc agccgctatt 1320

gcgtctaatt gctattcctc attgatcctg gattacttca gttaccccct ctctatgaag 1380

agcgatctct cggttagtag cgctgggcct atttcccagt ttaactacaa acaatccttt 1440

tccaatccaa catgcctgat cttagctact gtaccccaca acctgactac tattacgaag 1500

ccactcaagt actcatacat taataagtgc agccgattcc tcagtgatga tcgcaccgaa 1560

gtgccgcagc ttgtaaacgc gaaccagtac tccccatgcg tctctattgt gccttctaca 1620

gtgtgggaag acggcgatta ttatagaaag cagctgtcgc cactggaagg tggcgggtgg 1680

ctagttgcca gtgggtccac agttgccatg accgagcaac ttcagatggg gtttggcata 1740

acagtgcagt atggtaccga tacgaacagc gtgtgtccaa aattggaatt tgctaacgac 1800

accaagatcg cctcccagtt gggaaattgt gttgaatatt ccctgtacgg agtgtcaggc 1860

cggggggtgt tccaaaattg caccgccgtg ggagtgaggc agcaaagatt cgtgtacgac 1920

gcataccaga atctagtcgg atactattct gacgatggaa actactactg tctgcgcgct 1980

tgcgtctcag tgcccgtgag tgtcatatat gataaggaga ccaagactca cgctactctc 2040

tttggttctg tcgcgtgcga acacatttcc tctacaatgt cccagtatag tcgctccact 2100

cggtctatgt taaagcgcag agacagtacc tacggccctc tacagacacc tgtggggtgc 2160

gttctcggcc ttgtcaattc tagcctgttt gtggaggatt gtaagctgcc ccttggtcaa 2220

agcttatgcg cactgcccga tacgcccagc acacttacac cagcttcagt ggggtccgtc 2280

cccggggaaa tgagattggc ctcgatcgct ttcaaccacc ccatacaggt ggatcagctc 2340

aactcgtcat acttcaagct aagcatccct actaatttct cctttggtgt gactcaggag 2400

tacattcaga ccacaattca aaaggtgacc gttgactgca agcagtatgt gtgcaacggg 2460

ttccagaaat gtgaacagct gctccgggag tatggccagt tctgttctaa aatcaaccag 2520

gccctccacg gagcaaacct taggcaggac gattctgtca gaaacctctt tgccagcgtc 2580

aagagttctc agagttcccc tattatacct ggcttcggcg gggatttcaa cctgacacta 2640

cttgaacctg taagcatatc aaccggaagt cgcagtgccc gttccgccat cgaggatctg 2700

ctcttcgaca aagtaactat tgcagatccc ggatacatgc aggggtatga cgactgcatg 2760

cagcagggtc cagcctctgc aagggatctg atatgcgcac agtatgtcgc tgggtacaaa 2820

gtgttgcctc ctctcatgga cgtgaacatg gaagcggcct atacctcctc acttctaggc 2880

tccatagcgg gcgtgggatg gaccgcaggg ctttcaagct tcgccgcaat tccctttgct 2940

caatctatct tctacaggct taatggcgtt ggaatcaccc agcaggtgtt aagcgaaaac 3000

cagaaattga ttgccaataa gtttaaccaa gctttggggg ccatgcagac aggctttaca 3060

accacaaacg aggctttcca taaagtacag gatgcggtaa acaataacgc acaagccctg 3120

tcaaagctgg cttcagagct ctcaaataca tttggcgcta tatccgcgtc tatcggcgat 3180

atcatacaac ggttggaccc acccgaacag gacgcacaga ttgatcgttt gatcaacggg 3240

aggcttacca ccttaaacgc ttttgtggcc cagcaactgg tgcggtctga gagcgccgcc 3300

ttgagcgctc agctggcaaa ggataaagtg aatgaatgcg tgaaagctca atcaaagaga 3360

agtgggtttt gtgggcaggg tactcatatt gtttcctttg tggtgaacgc cccaaatgga 3420

ctctacttta tgcatgttgg atactacccg agcaaccaca tcgaggtcgt ttccgcctat 3480

gggctttgtg acgcagcaaa ccctactaac tgtatcgcgc cagttaatgg ctactttatt 3540

aaaacaaata acacacgcat tgtggatgaa tggagttaca cagggtccag cttctacgct 3600

ccagagccta tcacctctct gaacacaaag tatgtggcac ctcaggtcac atatcagaac 3660

atctcgacaa acctgccccc cccactcttg ggcaactcca cagggatcga cttccaggac 3720

gagcttgacg aattcttcaa gaacgtgtcc accagtatcc ctaattttgg ttcgctgacc 3780

caaattaaca caaccctgct cgatctgaca tatgaaatgc tttcactaca gcaggtggtc 3840

aaagcgttga acgagtcgta tatcgacctg aaagagttag ggaattacac atactataac 3900

aaatggccct ggtatatttg gttaggattc attgccgggc tggtggccct tgccttgtgc 3960

gtatttttca tcttgtcttt atggatgtgc tccaatggat cgttacaatg cagaatttgc 4020

atttga 4026

<210> 104

<211> 4017

<212> DNA

<213> artificial sequence

<220>

<223> PDI-MERS-H5iCT(V4)-DNA

<400> 104

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtatgtcga tgtgggtccc gatagtgtta agtccgcctg catcgaagtg 120

gacattcagc agaccttctt cgataagact tggcctcggc caattgatgt gtccaaggcc 180

gacggcatta tctaccccca aggtcggaca tattccaaca taactatcac ctatcagggg 240

ctattccctt atcagggcga ccatggggac atgtacgttt acagcgctgg tcacgctaca 300

gggacgaccc cccagaagct cttcgtggcg aactatagtc aggacgtgaa acagtttgcc 360

aacggttttg tagtgcgcat cggggcagcc gctaactcca ctggtactgt tattatcagc 420

ccttccacga gtgccacaat tcgaaagatc tatccggcct tcatgctagg atcctctgtg 480

ggcaatttta gcgacggtaa gatgggtcgg ttcttcaacc acacgcttgt gctgcttccc 540

gatgggtgcg gtactttgct gagggccttt tactgtatcc tagagccccg atccggcaac 600

cactgccccg ccgggaactc gtatacttcc tttgccactt atcatactcc agccacggat 660

tgtagcgatg ggaactacaa taggaacgcc agtttgaatt cctttaaaga gtacttcaac 720

ttgcggaatt gtaccttcat gtatacatat aacattactg aggacgaaat tctcgaatgg 780

ttcggaatca ctcaaacagc ccagggagtg cacctcttta gttctcgcta tgtggactta 840

tatggaggca atatgtttca attcgccacc ttacccgtct acgatacgat caagtattac 900

tcgatcatac cccactccat taggtccatt cagagcgatc gcaaggcatg ggccgcattc 960

tatgtgtata agctccagcc cctgaccttc ctcttggatt tctccgtgga cggctacatc 1020

agaagggcta tcgattgcgg gttcaacgac ctcagccagc tgcattgttc ttatgagagc 1080

tttgacgtgg aaagcggagt ttactcagtc tcttcctttg aggctaaacc ttcaggtagc 1140

gtcgtagagc aagcagaggg tgtggagtgc gatttctcac cactgctcag cggaacccca 1200

ccccaggtct acaactttaa gcggctcgtg ttcacaaact gtaactataa cttgactaag 1260

ttgctgtcac tcttttccgt gaatgatttt acatgctccc aaatcagccc agccgctatt 1320

gcgtctaatt gctattcctc attgatcctg gattacttca gttaccccct ctctatgaag 1380

agcgatctct cggttagtag cgctgggcct atttcccagt ttaactacaa acaatccttt 1440

tccaatccaa catgcctgat cttagctact gtaccccaca acctgactac tattacgaag 1500

ccactcaagt actcatacat taataagtgc agccgattcc tcagtgatga tcgcaccgaa 1560

gtgccgcagc ttgtaaacgc gaaccagtac tccccatgcg tctctattgt gccttctaca 1620

gtgtgggaag acggcgatta ttatagaaag cagctgtcgc cactggaagg tggcgggtgg 1680

ctagttgcca gtgggtccac agttgccatg accgagcaac ttcagatggg gtttggcata 1740

acagtgcagt atggtaccga tacgaacagc gtgtgtccaa aattggaatt tgctaacgac 1800

accaagatcg cctcccagtt gggaaattgt gttgaatatt ccctgtacgg agtgtcaggc 1860

cggggggtgt tccaaaattg caccgccgtg ggagtgaggc agcaaagatt cgtgtacgac 1920

gcataccaga atctagtcgg atactattct gacgatggaa actactactg tctgcgcgct 1980

tgcgtctcag tgcccgtgag tgtcatatat gataaggaga ccaagactca cgctactctc 2040

tttggttctg tcgcgtgcga acacatttcc tctacaatgt cccagtatag tcgctccact 2100

cggtctatgt taaagcgcag agacagtacc tacggccctc tacagacacc tgtggggtgc 2160

gttctcggcc ttgtcaattc tagcctgttt gtggaggatt gtaagctgcc ccttggtcaa 2220

agcttatgcg cactgcccga tacgcccagc acacttacac cagcttcagt ggggtccgtc 2280

cccggggaaa tgagattggc ctcgatcgct ttcaaccacc ccatacaggt ggatcagctc 2340

aactcgtcat acttcaagct aagcatccct actaatttct cctttggtgt gactcaggag 2400

tacattcaga ccacaattca aaaggtgacc gttgactgca agcagtatgt gtgcaacggg 2460

ttccagaaat gtgaacagct gctccgggag tatggccagt tctgttctaa aatcaaccag 2520

gccctccacg gagcaaacct taggcaggac gattctgtca gaaacctctt tgccagcgtc 2580

aagagttctc agagttcccc tattatacct ggcttcggcg gggatttcaa cctgacacta 2640

cttgaacctg taagcatatc aaccggaagt cgcagtgccc gttccgccat cgaggatctg 2700

ctcttcgaca aagtaactat tgcagatccc ggatacatgc aggggtatga cgactgcatg 2760

cagcagggtc cagcctctgc aagggatctg atatgcgcac agtatgtcgc tgggtacaaa 2820

gtgttgcctc ctctcatgga cgtgaacatg gaagcggcct atacctcctc acttctaggc 2880

tccatagcgg gcgtgggatg gaccgcaggg ctttcaagct tcgccgcaat tccctttgct 2940

caatctatct tctacaggct taatggcgtt ggaatcaccc agcaggtgtt aagcgaaaac 3000

cagaaattga ttgccaataa gtttaaccaa gctttggggg ccatgcagac aggctttaca 3060

accacaaacg aggctttcca taaagtacag gatgcggtaa acaataacgc acaagccctg 3120

tcaaagctgg cttcagagct ctcaaataca tttggcgcta tatccgcgtc tatcggcgat 3180

atcatacaac ggttggaccc acccgaacag gacgcacaga ttgatcgttt gatcaacggg 3240

aggcttacca ccttaaacgc ttttgtggcc cagcaactgg tgcggtctga gagcgccgcc 3300

ttgagcgctc agctggcaaa ggataaagtg aatgaatgcg tgaaagctca atcaaagaga 3360

agtgggtttt gtgggcaggg tactcatatt gtttcctttg tggtgaacgc cccaaatgga 3420

ctctacttta tgcatgttgg atactacccg agcaaccaca tcgaggtcgt ttccgcctat 3480

gggctttgtg acgcagcaaa ccctactaac tgtatcgcgc cagttaatgg ctactttatt 3540

aaaacaaata acacacgcat tgtggatgaa tggagttaca cagggtccag cttctacgct 3600

ccagagccta tcacctctct gaacacaaag tatgtggcac ctcaggtcac atatcagaac 3660

atctcgacaa acctgccccc cccactcttg ggcaactcca cagggatcga cttccaggac 3720

gagcttgacg aattcttcaa gaacgtgtcc accagtatcc ctaattttgg ttcgctgacc 3780

caaattaaca caaccctgct cgatctgaca tatgaaatgc tttcactaca gcaggtggtc 3840

aaagcgttga acgagtcgta tatcgacctg aaagagttag ggaattacac atactataac 3900

aaatggccct ggtatatttg gttaggattc attgccgggc tggtggccct tgccttgtgc 3960

gtatttttca tcttgtgctg ctccaatgga tcgttacaat gcagaatttg catttga 4017

<210> 105

<211> 4026

<212> DNA

<213> artificial sequence

<220>

<223> PDI-MERS-H1cCT-DNA

<400> 105

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgtatgtcga tgtgggtccc gatagtgtta agtccgcctg catcgaagtg 120

gacattcagc agaccttctt cgataagact tggcctcggc caattgatgt gtccaaggcc 180

gacggcatta tctaccccca aggtcggaca tattccaaca taactatcac ctatcagggg 240

ctattccctt atcagggcga ccatggggac atgtacgttt acagcgctgg tcacgctaca 300

gggacgaccc cccagaagct cttcgtggcg aactatagtc aggacgtgaa acagtttgcc 360

aacggttttg tagtgcgcat cggggcagcc gctaactcca ctggtactgt tattatcagc 420

ccttccacga gtgccacaat tcgaaagatc tatccggcct tcatgctagg atcctctgtg 480

ggcaatttta gcgacggtaa gatgggtcgg ttcttcaacc acacgcttgt gctgcttccc 540

gatgggtgcg gtactttgct gagggccttt tactgtatcc tagagccccg atccggcaac 600

cactgccccg ccgggaactc gtatacttcc tttgccactt atcatactcc agccacggat 660

tgtagcgatg ggaactacaa taggaacgcc agtttgaatt cctttaaaga gtacttcaac 720

ttgcggaatt gtaccttcat gtatacatat aacattactg aggacgaaat tctcgaatgg 780

ttcggaatca ctcaaacagc ccagggagtg cacctcttta gttctcgcta tgtggactta 840

tatggaggca atatgtttca attcgccacc ttacccgtct acgatacgat caagtattac 900

tcgatcatac cccactccat taggtccatt cagagcgatc gcaaggcatg ggccgcattc 960

tatgtgtata agctccagcc cctgaccttc ctcttggatt tctccgtgga cggctacatc 1020

agaagggcta tcgattgcgg gttcaacgac ctcagccagc tgcattgttc ttatgagagc 1080

tttgacgtgg aaagcggagt ttactcagtc tcttcctttg aggctaaacc ttcaggtagc 1140

gtcgtagagc aagcagaggg tgtggagtgc gatttctcac cactgctcag cggaacccca 1200

ccccaggtct acaactttaa gcggctcgtg ttcacaaact gtaactataa cttgactaag 1260

ttgctgtcac tcttttccgt gaatgatttt acatgctccc aaatcagccc agccgctatt 1320

gcgtctaatt gctattcctc attgatcctg gattacttca gttaccccct ctctatgaag 1380

agcgatctct cggttagtag cgctgggcct atttcccagt ttaactacaa acaatccttt 1440

tccaatccaa catgcctgat cttagctact gtaccccaca acctgactac tattacgaag 1500

ccactcaagt actcatacat taataagtgc agccgattcc tcagtgatga tcgcaccgaa 1560

gtgccgcagc ttgtaaacgc gaaccagtac tccccatgcg tctctattgt gccttctaca 1620

gtgtgggaag acggcgatta ttatagaaag cagctgtcgc cactggaagg tggcgggtgg 1680

ctagttgcca gtgggtccac agttgccatg accgagcaac ttcagatggg gtttggcata 1740

acagtgcagt atggtaccga tacgaacagc gtgtgtccaa aattggaatt tgctaacgac 1800

accaagatcg cctcccagtt gggaaattgt gttgaatatt ccctgtacgg agtgtcaggc 1860

cggggggtgt tccaaaattg caccgccgtg ggagtgaggc agcaaagatt cgtgtacgac 1920

gcataccaga atctagtcgg atactattct gacgatggaa actactactg tctgcgcgct 1980

tgcgtctcag tgcccgtgag tgtcatatat gataaggaga ccaagactca cgctactctc 2040

tttggttctg tcgcgtgcga acacatttcc tctacaatgt cccagtatag tcgctccact 2100

cggtctatgt taaagcgcag agacagtacc tacggccctc tacagacacc tgtggggtgc 2160

gttctcggcc ttgtcaattc tagcctgttt gtggaggatt gtaagctgcc ccttggtcaa 2220

agcttatgcg cactgcccga tacgcccagc acacttacac cagcttcagt ggggtccgtc 2280

cccggggaaa tgagattggc ctcgatcgct ttcaaccacc ccatacaggt ggatcagctc 2340

aactcgtcat acttcaagct aagcatccct actaatttct cctttggtgt gactcaggag 2400

tacattcaga ccacaattca aaaggtgacc gttgactgca agcagtatgt gtgcaacggg 2460

ttccagaaat gtgaacagct gctccgggag tatggccagt tctgttctaa aatcaaccag 2520

gccctccacg gagcaaacct taggcaggac gattctgtca gaaacctctt tgccagcgtc 2580

aagagttctc agagttcccc tattatacct ggcttcggcg gggatttcaa cctgacacta 2640

cttgaacctg taagcatatc aaccggaagt cgcagtgccc gttccgccat cgaggatctg 2700

ctcttcgaca aagtaactat tgcagatccc ggatacatgc aggggtatga cgactgcatg 2760

cagcagggtc cagcctctgc aagggatctg atatgcgcac agtatgtcgc tgggtacaaa 2820

gtgttgcctc ctctcatgga cgtgaacatg gaagcggcct atacctcctc acttctaggc 2880

tccatagcgg gcgtgggatg gaccgcaggg ctttcaagct tcgccgcaat tccctttgct 2940

caatctatct tctacaggct taatggcgtt ggaatcaccc agcaggtgtt aagcgaaaac 3000

cagaaattga ttgccaataa gtttaaccaa gctttggggg ccatgcagac aggctttaca 3060

accacaaacg aggctttcca taaagtacag gatgcggtaa acaataacgc acaagccctg 3120

tcaaagctgg cttcagagct ctcaaataca tttggcgcta tatccgcgtc tatcggcgat 3180

atcatacaac ggttggaccc acccgaacag gacgcacaga ttgatcgttt gatcaacggg 3240

aggcttacca ccttaaacgc ttttgtggcc cagcaactgg tgcggtctga gagcgccgcc 3300

ttgagcgctc agctggcaaa ggataaagtg aatgaatgcg tgaaagctca atcaaagaga 3360

agtgggtttt gtgggcaggg tactcatatt gtttcctttg tggtgaacgc cccaaatgga 3420

ctctacttta tgcatgttgg atactacccg agcaaccaca tcgaggtcgt ttccgcctat 3480

gggctttgtg acgcagcaaa ccctactaac tgtatcgcgc cagttaatgg ctactttatt 3540

aaaacaaata acacacgcat tgtggatgaa tggagttaca cagggtccag cttctacgct 3600

ccagagccta tcacctctct gaacacaaag tatgtggcac ctcaggtcac atatcagaac 3660

atctcgacaa acctgccccc cccactcttg ggcaactcca cagggatcga cttccaggac 3720

gagcttgacg aattcttcaa gaacgtgtcc accagtatcc ctaattttgg ttcgctgacc 3780

caaattaaca caaccctgct cgatctgaca tatgaaatgc tttcactaca gcaggtggtc 3840

aaagcgttga acgagtcgta tatcgacctg aaagagttag ggaattacac atactataac 3900

aaatggccct ggtatatttg gttaggattc attgccgggc tggtggccct tgccttgtgc 3960

gtatttttca tcttgagctt ctggatgtgc tctaatgggt ctctacagtg tagaatatgt 4020

atttga 4026

<210> 106

<211> 1360

<212> PRT

<213> artificial sequence

<220>

<223> PDI-MERS-wtTMCT-AA

<400> 106

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Tyr Val Asp Val Gly Pro Asp Ser

20 25 30

Val Lys Ser Ala Cys Ile Glu Val Asp Ile Gln Gln Thr Phe Phe Asp

35 40 45

Lys Thr Trp Pro Arg Pro Ile Asp Val Ser Lys Ala Asp Gly Ile Ile

50 55 60

Tyr Pro Gln Gly Arg Thr Tyr Ser Asn Ile Thr Ile Thr Tyr Gln Gly

65 70 75 80

Leu Phe Pro Tyr Gln Gly Asp His Gly Asp Met Tyr Val Tyr Ser Ala

85 90 95

Gly His Ala Thr Gly Thr Thr Pro Gln Lys Leu Phe Val Ala Asn Tyr

100 105 110

Ser Gln Asp Val Lys Gln Phe Ala Asn Gly Phe Val Val Arg Ile Gly

115 120 125

Ala Ala Ala Asn Ser Thr Gly Thr Val Ile Ile Ser Pro Ser Thr Ser

130 135 140

Ala Thr Ile Arg Lys Ile Tyr Pro Ala Phe Met Leu Gly Ser Ser Val

145 150 155 160

Gly Asn Phe Ser Asp Gly Lys Met Gly Arg Phe Phe Asn His Thr Leu

165 170 175

Val Leu Leu Pro Asp Gly Cys Gly Thr Leu Leu Arg Ala Phe Tyr Cys

180 185 190

Ile Leu Glu Pro Arg Ser Gly Asn His Cys Pro Ala Gly Asn Ser Tyr

195 200 205

Thr Ser Phe Ala Thr Tyr His Thr Pro Ala Thr Asp Cys Ser Asp Gly

210 215 220

Asn Tyr Asn Arg Asn Ala Ser Leu Asn Ser Phe Lys Glu Tyr Phe Asn

225 230 235 240

Leu Arg Asn Cys Thr Phe Met Tyr Thr Tyr Asn Ile Thr Glu Asp Glu

245 250 255

Ile Leu Glu Trp Phe Gly Ile Thr Gln Thr Ala Gln Gly Val His Leu

260 265 270

Phe Ser Ser Arg Tyr Val Asp Leu Tyr Gly Gly Asn Met Phe Gln Phe

275 280 285

Ala Thr Leu Pro Val Tyr Asp Thr Ile Lys Tyr Tyr Ser Ile Ile Pro

290 295 300

His Ser Ile Arg Ser Ile Gln Ser Asp Arg Lys Ala Trp Ala Ala Phe

305 310 315 320

Tyr Val Tyr Lys Leu Gln Pro Leu Thr Phe Leu Leu Asp Phe Ser Val

325 330 335

Asp Gly Tyr Ile Arg Arg Ala Ile Asp Cys Gly Phe Asn Asp Leu Ser

340 345 350

Gln Leu His Cys Ser Tyr Glu Ser Phe Asp Val Glu Ser Gly Val Tyr

355 360 365

Ser Val Ser Ser Phe Glu Ala Lys Pro Ser Gly Ser Val Val Glu Gln

370 375 380

Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro

385 390 395 400

Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr

405 410 415

Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys

420 425 430

Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu

435 440 445

Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser

450 455 460

Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe

465 470 475 480

Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr

485 490 495

Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg

500 505 510

Phe Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn Ala Asn

515 520 525

Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp

530 535 540

Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp

545 550 555 560

Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu Gln Met

565 570 575

Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys

580 585 590

Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly

595 600 605

Asn Cys Val Glu Tyr Ser Leu Tyr Gly Val Ser Gly Arg Gly Val Phe

610 615 620

Gln Asn Cys Thr Ala Val Gly Val Arg Gln Gln Arg Phe Val Tyr Asp

625 630 635 640

Ala Tyr Gln Asn Leu Val Gly Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr

645 650 655

Cys Leu Arg Ala Cys Val Ser Val Pro Val Ser Val Ile Tyr Asp Lys

660 665 670

Glu Thr Lys Thr His Ala Thr Leu Phe Gly Ser Val Ala Cys Glu His

675 680 685

Ile Ser Ser Thr Met Ser Gln Tyr Ser Arg Ser Thr Arg Ser Met Leu

690 695 700

Lys Arg Arg Asp Ser Thr Tyr Gly Pro Leu Gln Thr Pro Val Gly Cys

705 710 715 720

Val Leu Gly Leu Val Asn Ser Ser Leu Phe Val Glu Asp Cys Lys Leu

725 730 735

Pro Leu Gly Gln Ser Leu Cys Ala Leu Pro Asp Thr Pro Ser Thr Leu

740 745 750

Thr Pro Ala Ser Val Gly Ser Val Pro Gly Glu Met Arg Leu Ala Ser

755 760 765

Ile Ala Phe Asn His Pro Ile Gln Val Asp Gln Leu Asn Ser Ser Tyr

770 775 780

Phe Lys Leu Ser Ile Pro Thr Asn Phe Ser Phe Gly Val Thr Gln Glu

785 790 795 800

Tyr Ile Gln Thr Thr Ile Gln Lys Val Thr Val Asp Cys Lys Gln Tyr

805 810 815

Val Cys Asn Gly Phe Gln Lys Cys Glu Gln Leu Leu Arg Glu Tyr Gly

820 825 830

Gln Phe Cys Ser Lys Ile Asn Gln Ala Leu His Gly Ala Asn Leu Arg

835 840 845

Gln Asp Asp Ser Val Arg Asn Leu Phe Ala Ser Val Lys Ser Ser Gln

850 855 860

Ser Ser Pro Ile Ile Pro Gly Phe Gly Gly Asp Phe Asn Leu Thr Leu

865 870 875 880

Leu Glu Pro Val Ser Ile Ser Thr Gly Ser Arg Ser Ala Arg Ser Ala

885 890 895

Ile Glu Asp Leu Leu Phe Asp Lys Val Thr Ile Ala Asp Pro Gly Tyr

900 905 910

Met Gln Gly Tyr Asp Asp Cys Met Gln Gln Gly Pro Ala Ser Ala Arg

915 920 925

Asp Leu Ile Cys Ala Gln Tyr Val Ala Gly Tyr Lys Val Leu Pro Pro

930 935 940

Leu Met Asp Val Asn Met Glu Ala Ala Tyr Thr Ser Ser Leu Leu Gly

945 950 955 960

Ser Ile Ala Gly Val Gly Trp Thr Ala Gly Leu Ser Ser Phe Ala Ala

965 970 975

Ile Pro Phe Ala Gln Ser Ile Phe Tyr Arg Leu Asn Gly Val Gly Ile

980 985 990

Thr Gln Gln Val Leu Ser Glu Asn Gln Lys Leu Ile Ala Asn Lys Phe

995 1000 1005

Asn Gln Ala Leu Gly Ala Met Gln Thr Gly Phe Thr Thr Thr Asn Glu

1010 1015 1020

Ala Phe His Lys Val Gln Asp Ala Val Asn Asn Asn Ala Gln Ala Leu

1025 1030 1035 1040

Ser Lys Leu Ala Ser Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala

1045 1050 1055

Ser Ile Gly Asp Ile Ile Gln Arg Leu Asp Pro Pro Glu Gln Asp Ala

1060 1065 1070

Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe

1075 1080 1085

Val Ala Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln

1090 1095 1100

Leu Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg

1105 1110 1115 1120

Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val Asn

1125 1130 1135

Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro Ser Asn

1140 1145 1150

His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala Ala Asn Pro

1155 1160 1165

Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile Lys Thr Asn Asn

1170 1175 1180

Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly Ser Ser Phe Tyr Ala

1185 1190 1195 1200

Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys Tyr Val Ala Pro Gln Val

1205 1210 1215

Thr Tyr Gln Asn Ile Ser Thr Asn Leu Pro Pro Pro Leu Leu Gly Asn

1220 1225 1230

Ser Thr Gly Ile Asp Phe Gln Asp Glu Leu Asp Glu Phe Phe Lys Asn

1235 1240 1245

Val Ser Thr Ser Ile Pro Asn Phe Gly Ser Leu Thr Gln Ile Asn Thr

1250 1255 1260

Thr Leu Leu Asp Leu Thr Tyr Glu Met Leu Ser Leu Gln Gln Val Val

1265 1270 1275 1280

Lys Ala Leu Asn Glu Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr

1285 1290 1295

Thr Tyr Tyr Asn Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala

1300 1305 1310

Gly Leu Val Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Cys Cys Thr

1315 1320 1325

Gly Cys Gly Thr Asn Cys Met Gly Lys Leu Lys Cys Asn Arg Cys Cys

1330 1335 1340

Asp Arg Tyr Glu Glu Tyr Asp Leu Glu Pro His Lys Val His Val His

1345 1350 1355 1360

<210> 107

<211> 1343

<212> PRT

<213> artificial sequence

<220>

<223> PDI-MERS-H5iTMCT-AA

<400> 107

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Tyr Val Asp Val Gly Pro Asp Ser

20 25 30

Val Lys Ser Ala Cys Ile Glu Val Asp Ile Gln Gln Thr Phe Phe Asp

35 40 45

Lys Thr Trp Pro Arg Pro Ile Asp Val Ser Lys Ala Asp Gly Ile Ile

50 55 60

Tyr Pro Gln Gly Arg Thr Tyr Ser Asn Ile Thr Ile Thr Tyr Gln Gly

65 70 75 80

Leu Phe Pro Tyr Gln Gly Asp His Gly Asp Met Tyr Val Tyr Ser Ala

85 90 95

Gly His Ala Thr Gly Thr Thr Pro Gln Lys Leu Phe Val Ala Asn Tyr

100 105 110

Ser Gln Asp Val Lys Gln Phe Ala Asn Gly Phe Val Val Arg Ile Gly

115 120 125

Ala Ala Ala Asn Ser Thr Gly Thr Val Ile Ile Ser Pro Ser Thr Ser

130 135 140

Ala Thr Ile Arg Lys Ile Tyr Pro Ala Phe Met Leu Gly Ser Ser Val

145 150 155 160

Gly Asn Phe Ser Asp Gly Lys Met Gly Arg Phe Phe Asn His Thr Leu

165 170 175

Val Leu Leu Pro Asp Gly Cys Gly Thr Leu Leu Arg Ala Phe Tyr Cys

180 185 190

Ile Leu Glu Pro Arg Ser Gly Asn His Cys Pro Ala Gly Asn Ser Tyr

195 200 205

Thr Ser Phe Ala Thr Tyr His Thr Pro Ala Thr Asp Cys Ser Asp Gly

210 215 220

Asn Tyr Asn Arg Asn Ala Ser Leu Asn Ser Phe Lys Glu Tyr Phe Asn

225 230 235 240

Leu Arg Asn Cys Thr Phe Met Tyr Thr Tyr Asn Ile Thr Glu Asp Glu

245 250 255

Ile Leu Glu Trp Phe Gly Ile Thr Gln Thr Ala Gln Gly Val His Leu

260 265 270

Phe Ser Ser Arg Tyr Val Asp Leu Tyr Gly Gly Asn Met Phe Gln Phe

275 280 285

Ala Thr Leu Pro Val Tyr Asp Thr Ile Lys Tyr Tyr Ser Ile Ile Pro

290 295 300

His Ser Ile Arg Ser Ile Gln Ser Asp Arg Lys Ala Trp Ala Ala Phe

305 310 315 320

Tyr Val Tyr Lys Leu Gln Pro Leu Thr Phe Leu Leu Asp Phe Ser Val

325 330 335

Asp Gly Tyr Ile Arg Arg Ala Ile Asp Cys Gly Phe Asn Asp Leu Ser

340 345 350

Gln Leu His Cys Ser Tyr Glu Ser Phe Asp Val Glu Ser Gly Val Tyr

355 360 365

Ser Val Ser Ser Phe Glu Ala Lys Pro Ser Gly Ser Val Val Glu Gln

370 375 380

Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro

385 390 395 400

Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr

405 410 415

Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys

420 425 430

Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu

435 440 445

Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser

450 455 460

Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe

465 470 475 480

Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr

485 490 495

Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg

500 505 510

Phe Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn Ala Asn

515 520 525

Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp

530 535 540

Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp

545 550 555 560

Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu Gln Met

565 570 575

Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys

580 585 590

Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly

595 600 605

Asn Cys Val Glu Tyr Ser Leu Tyr Gly Val Ser Gly Arg Gly Val Phe

610 615 620

Gln Asn Cys Thr Ala Val Gly Val Arg Gln Gln Arg Phe Val Tyr Asp

625 630 635 640

Ala Tyr Gln Asn Leu Val Gly Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr

645 650 655

Cys Leu Arg Ala Cys Val Ser Val Pro Val Ser Val Ile Tyr Asp Lys

660 665 670

Glu Thr Lys Thr His Ala Thr Leu Phe Gly Ser Val Ala Cys Glu His

675 680 685

Ile Ser Ser Thr Met Ser Gln Tyr Ser Arg Ser Thr Arg Ser Met Leu

690 695 700

Lys Arg Arg Asp Ser Thr Tyr Gly Pro Leu Gln Thr Pro Val Gly Cys

705 710 715 720

Val Leu Gly Leu Val Asn Ser Ser Leu Phe Val Glu Asp Cys Lys Leu

725 730 735

Pro Leu Gly Gln Ser Leu Cys Ala Leu Pro Asp Thr Pro Ser Thr Leu

740 745 750

Thr Pro Ala Ser Val Gly Ser Val Pro Gly Glu Met Arg Leu Ala Ser

755 760 765

Ile Ala Phe Asn His Pro Ile Gln Val Asp Gln Leu Asn Ser Ser Tyr

770 775 780

Phe Lys Leu Ser Ile Pro Thr Asn Phe Ser Phe Gly Val Thr Gln Glu

785 790 795 800

Tyr Ile Gln Thr Thr Ile Gln Lys Val Thr Val Asp Cys Lys Gln Tyr

805 810 815

Val Cys Asn Gly Phe Gln Lys Cys Glu Gln Leu Leu Arg Glu Tyr Gly

820 825 830

Gln Phe Cys Ser Lys Ile Asn Gln Ala Leu His Gly Ala Asn Leu Arg

835 840 845

Gln Asp Asp Ser Val Arg Asn Leu Phe Ala Ser Val Lys Ser Ser Gln

850 855 860

Ser Ser Pro Ile Ile Pro Gly Phe Gly Gly Asp Phe Asn Leu Thr Leu

865 870 875 880

Leu Glu Pro Val Ser Ile Ser Thr Gly Ser Arg Ser Ala Arg Ser Ala

885 890 895

Ile Glu Asp Leu Leu Phe Asp Lys Val Thr Ile Ala Asp Pro Gly Tyr

900 905 910

Met Gln Gly Tyr Asp Asp Cys Met Gln Gln Gly Pro Ala Ser Ala Arg

915 920 925

Asp Leu Ile Cys Ala Gln Tyr Val Ala Gly Tyr Lys Val Leu Pro Pro

930 935 940

Leu Met Asp Val Asn Met Glu Ala Ala Tyr Thr Ser Ser Leu Leu Gly

945 950 955 960

Ser Ile Ala Gly Val Gly Trp Thr Ala Gly Leu Ser Ser Phe Ala Ala

965 970 975

Ile Pro Phe Ala Gln Ser Ile Phe Tyr Arg Leu Asn Gly Val Gly Ile

980 985 990

Thr Gln Gln Val Leu Ser Glu Asn Gln Lys Leu Ile Ala Asn Lys Phe

995 1000 1005

Asn Gln Ala Leu Gly Ala Met Gln Thr Gly Phe Thr Thr Thr Asn Glu

1010 1015 1020

Ala Phe His Lys Val Gln Asp Ala Val Asn Asn Asn Ala Gln Ala Leu

1025 1030 1035 1040

Ser Lys Leu Ala Ser Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala

1045 1050 1055

Ser Ile Gly Asp Ile Ile Gln Arg Leu Asp Pro Pro Glu Gln Asp Ala

1060 1065 1070

Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe

1075 1080 1085

Val Ala Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln

1090 1095 1100

Leu Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg

1105 1110 1115 1120

Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val Asn

1125 1130 1135

Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro Ser Asn

1140 1145 1150

His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala Ala Asn Pro

1155 1160 1165

Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile Lys Thr Asn Asn

1170 1175 1180

Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly Ser Ser Phe Tyr Ala

1185 1190 1195 1200

Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys Tyr Val Ala Pro Gln Val

1205 1210 1215

Thr Tyr Gln Asn Ile Ser Thr Asn Leu Pro Pro Pro Leu Leu Gly Asn

1220 1225 1230

Ser Thr Gly Ile Asp Phe Gln Asp Glu Leu Asp Glu Phe Phe Lys Asn

1235 1240 1245

Val Ser Thr Ser Ile Pro Asn Phe Gly Ser Leu Thr Gln Ile Asn Thr

1250 1255 1260

Thr Leu Leu Asp Leu Thr Tyr Glu Met Leu Ser Leu Gln Gln Val Val

1265 1270 1275 1280

Lys Ala Leu Asn Glu Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr

1285 1290 1295

Thr Tyr Tyr Asn Lys Trp Pro Trp Tyr Gln Ile Leu Ser Ile Tyr Ser

1300 1305 1310

Thr Val Ala Ser Ser Leu Ala Leu Ala Ile Met Met Ala Gly Leu Ser

1315 1320 1325

Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1330 1335 1340

<210> 108

<211> 1341

<212> PRT

<213> artificial sequence

<220>

<223> PDI-MERS-H5iCT-AA

<400> 108

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Tyr Val Asp Val Gly Pro Asp Ser

20 25 30

Val Lys Ser Ala Cys Ile Glu Val Asp Ile Gln Gln Thr Phe Phe Asp

35 40 45

Lys Thr Trp Pro Arg Pro Ile Asp Val Ser Lys Ala Asp Gly Ile Ile

50 55 60

Tyr Pro Gln Gly Arg Thr Tyr Ser Asn Ile Thr Ile Thr Tyr Gln Gly

65 70 75 80

Leu Phe Pro Tyr Gln Gly Asp His Gly Asp Met Tyr Val Tyr Ser Ala

85 90 95

Gly His Ala Thr Gly Thr Thr Pro Gln Lys Leu Phe Val Ala Asn Tyr

100 105 110

Ser Gln Asp Val Lys Gln Phe Ala Asn Gly Phe Val Val Arg Ile Gly

115 120 125

Ala Ala Ala Asn Ser Thr Gly Thr Val Ile Ile Ser Pro Ser Thr Ser

130 135 140

Ala Thr Ile Arg Lys Ile Tyr Pro Ala Phe Met Leu Gly Ser Ser Val

145 150 155 160

Gly Asn Phe Ser Asp Gly Lys Met Gly Arg Phe Phe Asn His Thr Leu

165 170 175

Val Leu Leu Pro Asp Gly Cys Gly Thr Leu Leu Arg Ala Phe Tyr Cys

180 185 190

Ile Leu Glu Pro Arg Ser Gly Asn His Cys Pro Ala Gly Asn Ser Tyr

195 200 205

Thr Ser Phe Ala Thr Tyr His Thr Pro Ala Thr Asp Cys Ser Asp Gly

210 215 220

Asn Tyr Asn Arg Asn Ala Ser Leu Asn Ser Phe Lys Glu Tyr Phe Asn

225 230 235 240

Leu Arg Asn Cys Thr Phe Met Tyr Thr Tyr Asn Ile Thr Glu Asp Glu

245 250 255

Ile Leu Glu Trp Phe Gly Ile Thr Gln Thr Ala Gln Gly Val His Leu

260 265 270

Phe Ser Ser Arg Tyr Val Asp Leu Tyr Gly Gly Asn Met Phe Gln Phe

275 280 285

Ala Thr Leu Pro Val Tyr Asp Thr Ile Lys Tyr Tyr Ser Ile Ile Pro

290 295 300

His Ser Ile Arg Ser Ile Gln Ser Asp Arg Lys Ala Trp Ala Ala Phe

305 310 315 320

Tyr Val Tyr Lys Leu Gln Pro Leu Thr Phe Leu Leu Asp Phe Ser Val

325 330 335

Asp Gly Tyr Ile Arg Arg Ala Ile Asp Cys Gly Phe Asn Asp Leu Ser

340 345 350

Gln Leu His Cys Ser Tyr Glu Ser Phe Asp Val Glu Ser Gly Val Tyr

355 360 365

Ser Val Ser Ser Phe Glu Ala Lys Pro Ser Gly Ser Val Val Glu Gln

370 375 380

Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro

385 390 395 400

Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr

405 410 415

Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys

420 425 430

Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu

435 440 445

Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser

450 455 460

Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe

465 470 475 480

Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr

485 490 495

Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg

500 505 510

Phe Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn Ala Asn

515 520 525

Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp

530 535 540

Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp

545 550 555 560

Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu Gln Met

565 570 575

Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys

580 585 590

Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly

595 600 605

Asn Cys Val Glu Tyr Ser Leu Tyr Gly Val Ser Gly Arg Gly Val Phe

610 615 620

Gln Asn Cys Thr Ala Val Gly Val Arg Gln Gln Arg Phe Val Tyr Asp

625 630 635 640

Ala Tyr Gln Asn Leu Val Gly Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr

645 650 655

Cys Leu Arg Ala Cys Val Ser Val Pro Val Ser Val Ile Tyr Asp Lys

660 665 670

Glu Thr Lys Thr His Ala Thr Leu Phe Gly Ser Val Ala Cys Glu His

675 680 685

Ile Ser Ser Thr Met Ser Gln Tyr Ser Arg Ser Thr Arg Ser Met Leu

690 695 700

Lys Arg Arg Asp Ser Thr Tyr Gly Pro Leu Gln Thr Pro Val Gly Cys

705 710 715 720

Val Leu Gly Leu Val Asn Ser Ser Leu Phe Val Glu Asp Cys Lys Leu

725 730 735

Pro Leu Gly Gln Ser Leu Cys Ala Leu Pro Asp Thr Pro Ser Thr Leu

740 745 750

Thr Pro Ala Ser Val Gly Ser Val Pro Gly Glu Met Arg Leu Ala Ser

755 760 765

Ile Ala Phe Asn His Pro Ile Gln Val Asp Gln Leu Asn Ser Ser Tyr

770 775 780

Phe Lys Leu Ser Ile Pro Thr Asn Phe Ser Phe Gly Val Thr Gln Glu

785 790 795 800

Tyr Ile Gln Thr Thr Ile Gln Lys Val Thr Val Asp Cys Lys Gln Tyr

805 810 815

Val Cys Asn Gly Phe Gln Lys Cys Glu Gln Leu Leu Arg Glu Tyr Gly

820 825 830

Gln Phe Cys Ser Lys Ile Asn Gln Ala Leu His Gly Ala Asn Leu Arg

835 840 845

Gln Asp Asp Ser Val Arg Asn Leu Phe Ala Ser Val Lys Ser Ser Gln

850 855 860

Ser Ser Pro Ile Ile Pro Gly Phe Gly Gly Asp Phe Asn Leu Thr Leu

865 870 875 880

Leu Glu Pro Val Ser Ile Ser Thr Gly Ser Arg Ser Ala Arg Ser Ala

885 890 895

Ile Glu Asp Leu Leu Phe Asp Lys Val Thr Ile Ala Asp Pro Gly Tyr

900 905 910

Met Gln Gly Tyr Asp Asp Cys Met Gln Gln Gly Pro Ala Ser Ala Arg

915 920 925

Asp Leu Ile Cys Ala Gln Tyr Val Ala Gly Tyr Lys Val Leu Pro Pro

930 935 940

Leu Met Asp Val Asn Met Glu Ala Ala Tyr Thr Ser Ser Leu Leu Gly

945 950 955 960

Ser Ile Ala Gly Val Gly Trp Thr Ala Gly Leu Ser Ser Phe Ala Ala

965 970 975

Ile Pro Phe Ala Gln Ser Ile Phe Tyr Arg Leu Asn Gly Val Gly Ile

980 985 990

Thr Gln Gln Val Leu Ser Glu Asn Gln Lys Leu Ile Ala Asn Lys Phe

995 1000 1005

Asn Gln Ala Leu Gly Ala Met Gln Thr Gly Phe Thr Thr Thr Asn Glu

1010 1015 1020

Ala Phe His Lys Val Gln Asp Ala Val Asn Asn Asn Ala Gln Ala Leu

1025 1030 1035 1040

Ser Lys Leu Ala Ser Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala

1045 1050 1055

Ser Ile Gly Asp Ile Ile Gln Arg Leu Asp Pro Pro Glu Gln Asp Ala

1060 1065 1070

Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe

1075 1080 1085

Val Ala Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln

1090 1095 1100

Leu Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg

1105 1110 1115 1120

Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val Asn

1125 1130 1135

Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro Ser Asn

1140 1145 1150

His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala Ala Asn Pro

1155 1160 1165

Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile Lys Thr Asn Asn

1170 1175 1180

Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly Ser Ser Phe Tyr Ala

1185 1190 1195 1200

Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys Tyr Val Ala Pro Gln Val

1205 1210 1215

Thr Tyr Gln Asn Ile Ser Thr Asn Leu Pro Pro Pro Leu Leu Gly Asn

1220 1225 1230

Ser Thr Gly Ile Asp Phe Gln Asp Glu Leu Asp Glu Phe Phe Lys Asn

1235 1240 1245

Val Ser Thr Ser Ile Pro Asn Phe Gly Ser Leu Thr Gln Ile Asn Thr

1250 1255 1260

Thr Leu Leu Asp Leu Thr Tyr Glu Met Leu Ser Leu Gln Gln Val Val

1265 1270 1275 1280

Lys Ala Leu Asn Glu Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr

1285 1290 1295

Thr Tyr Tyr Asn Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala

1300 1305 1310

Gly Leu Val Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Ser Leu Trp

1315 1320 1325

Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1330 1335 1340

<210> 109

<211> 1338

<212> PRT

<213> artificial sequence

<220>

<223> PDI-MERS-H5iCT(V4)-AA

<400> 109

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Tyr Val Asp Val Gly Pro Asp Ser

20 25 30

Val Lys Ser Ala Cys Ile Glu Val Asp Ile Gln Gln Thr Phe Phe Asp

35 40 45

Lys Thr Trp Pro Arg Pro Ile Asp Val Ser Lys Ala Asp Gly Ile Ile

50 55 60

Tyr Pro Gln Gly Arg Thr Tyr Ser Asn Ile Thr Ile Thr Tyr Gln Gly

65 70 75 80

Leu Phe Pro Tyr Gln Gly Asp His Gly Asp Met Tyr Val Tyr Ser Ala

85 90 95

Gly His Ala Thr Gly Thr Thr Pro Gln Lys Leu Phe Val Ala Asn Tyr

100 105 110

Ser Gln Asp Val Lys Gln Phe Ala Asn Gly Phe Val Val Arg Ile Gly

115 120 125

Ala Ala Ala Asn Ser Thr Gly Thr Val Ile Ile Ser Pro Ser Thr Ser

130 135 140

Ala Thr Ile Arg Lys Ile Tyr Pro Ala Phe Met Leu Gly Ser Ser Val

145 150 155 160

Gly Asn Phe Ser Asp Gly Lys Met Gly Arg Phe Phe Asn His Thr Leu

165 170 175

Val Leu Leu Pro Asp Gly Cys Gly Thr Leu Leu Arg Ala Phe Tyr Cys

180 185 190

Ile Leu Glu Pro Arg Ser Gly Asn His Cys Pro Ala Gly Asn Ser Tyr

195 200 205

Thr Ser Phe Ala Thr Tyr His Thr Pro Ala Thr Asp Cys Ser Asp Gly

210 215 220

Asn Tyr Asn Arg Asn Ala Ser Leu Asn Ser Phe Lys Glu Tyr Phe Asn

225 230 235 240

Leu Arg Asn Cys Thr Phe Met Tyr Thr Tyr Asn Ile Thr Glu Asp Glu

245 250 255

Ile Leu Glu Trp Phe Gly Ile Thr Gln Thr Ala Gln Gly Val His Leu

260 265 270

Phe Ser Ser Arg Tyr Val Asp Leu Tyr Gly Gly Asn Met Phe Gln Phe

275 280 285

Ala Thr Leu Pro Val Tyr Asp Thr Ile Lys Tyr Tyr Ser Ile Ile Pro

290 295 300

His Ser Ile Arg Ser Ile Gln Ser Asp Arg Lys Ala Trp Ala Ala Phe

305 310 315 320

Tyr Val Tyr Lys Leu Gln Pro Leu Thr Phe Leu Leu Asp Phe Ser Val

325 330 335

Asp Gly Tyr Ile Arg Arg Ala Ile Asp Cys Gly Phe Asn Asp Leu Ser

340 345 350

Gln Leu His Cys Ser Tyr Glu Ser Phe Asp Val Glu Ser Gly Val Tyr

355 360 365

Ser Val Ser Ser Phe Glu Ala Lys Pro Ser Gly Ser Val Val Glu Gln

370 375 380

Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro

385 390 395 400

Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr

405 410 415

Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys

420 425 430

Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu

435 440 445

Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser

450 455 460

Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe

465 470 475 480

Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr

485 490 495

Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg

500 505 510

Phe Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn Ala Asn

515 520 525

Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp

530 535 540

Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp

545 550 555 560

Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu Gln Met

565 570 575

Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys

580 585 590

Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly

595 600 605

Asn Cys Val Glu Tyr Ser Leu Tyr Gly Val Ser Gly Arg Gly Val Phe

610 615 620

Gln Asn Cys Thr Ala Val Gly Val Arg Gln Gln Arg Phe Val Tyr Asp

625 630 635 640

Ala Tyr Gln Asn Leu Val Gly Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr

645 650 655

Cys Leu Arg Ala Cys Val Ser Val Pro Val Ser Val Ile Tyr Asp Lys

660 665 670

Glu Thr Lys Thr His Ala Thr Leu Phe Gly Ser Val Ala Cys Glu His

675 680 685

Ile Ser Ser Thr Met Ser Gln Tyr Ser Arg Ser Thr Arg Ser Met Leu

690 695 700

Lys Arg Arg Asp Ser Thr Tyr Gly Pro Leu Gln Thr Pro Val Gly Cys

705 710 715 720

Val Leu Gly Leu Val Asn Ser Ser Leu Phe Val Glu Asp Cys Lys Leu

725 730 735

Pro Leu Gly Gln Ser Leu Cys Ala Leu Pro Asp Thr Pro Ser Thr Leu

740 745 750

Thr Pro Ala Ser Val Gly Ser Val Pro Gly Glu Met Arg Leu Ala Ser

755 760 765

Ile Ala Phe Asn His Pro Ile Gln Val Asp Gln Leu Asn Ser Ser Tyr

770 775 780

Phe Lys Leu Ser Ile Pro Thr Asn Phe Ser Phe Gly Val Thr Gln Glu

785 790 795 800

Tyr Ile Gln Thr Thr Ile Gln Lys Val Thr Val Asp Cys Lys Gln Tyr

805 810 815

Val Cys Asn Gly Phe Gln Lys Cys Glu Gln Leu Leu Arg Glu Tyr Gly

820 825 830

Gln Phe Cys Ser Lys Ile Asn Gln Ala Leu His Gly Ala Asn Leu Arg

835 840 845

Gln Asp Asp Ser Val Arg Asn Leu Phe Ala Ser Val Lys Ser Ser Gln

850 855 860

Ser Ser Pro Ile Ile Pro Gly Phe Gly Gly Asp Phe Asn Leu Thr Leu

865 870 875 880

Leu Glu Pro Val Ser Ile Ser Thr Gly Ser Arg Ser Ala Arg Ser Ala

885 890 895

Ile Glu Asp Leu Leu Phe Asp Lys Val Thr Ile Ala Asp Pro Gly Tyr

900 905 910

Met Gln Gly Tyr Asp Asp Cys Met Gln Gln Gly Pro Ala Ser Ala Arg

915 920 925

Asp Leu Ile Cys Ala Gln Tyr Val Ala Gly Tyr Lys Val Leu Pro Pro

930 935 940

Leu Met Asp Val Asn Met Glu Ala Ala Tyr Thr Ser Ser Leu Leu Gly

945 950 955 960

Ser Ile Ala Gly Val Gly Trp Thr Ala Gly Leu Ser Ser Phe Ala Ala

965 970 975

Ile Pro Phe Ala Gln Ser Ile Phe Tyr Arg Leu Asn Gly Val Gly Ile

980 985 990

Thr Gln Gln Val Leu Ser Glu Asn Gln Lys Leu Ile Ala Asn Lys Phe

995 1000 1005

Asn Gln Ala Leu Gly Ala Met Gln Thr Gly Phe Thr Thr Thr Asn Glu

1010 1015 1020

Ala Phe His Lys Val Gln Asp Ala Val Asn Asn Asn Ala Gln Ala Leu

1025 1030 1035 1040

Ser Lys Leu Ala Ser Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala

1045 1050 1055

Ser Ile Gly Asp Ile Ile Gln Arg Leu Asp Pro Pro Glu Gln Asp Ala

1060 1065 1070

Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe

1075 1080 1085

Val Ala Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln

1090 1095 1100

Leu Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg

1105 1110 1115 1120

Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val Asn

1125 1130 1135

Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro Ser Asn

1140 1145 1150

His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala Ala Asn Pro

1155 1160 1165

Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile Lys Thr Asn Asn

1170 1175 1180

Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly Ser Ser Phe Tyr Ala

1185 1190 1195 1200

Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys Tyr Val Ala Pro Gln Val

1205 1210 1215

Thr Tyr Gln Asn Ile Ser Thr Asn Leu Pro Pro Pro Leu Leu Gly Asn

1220 1225 1230

Ser Thr Gly Ile Asp Phe Gln Asp Glu Leu Asp Glu Phe Phe Lys Asn

1235 1240 1245

Val Ser Thr Ser Ile Pro Asn Phe Gly Ser Leu Thr Gln Ile Asn Thr

1250 1255 1260

Thr Leu Leu Asp Leu Thr Tyr Glu Met Leu Ser Leu Gln Gln Val Val

1265 1270 1275 1280

Lys Ala Leu Asn Glu Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr

1285 1290 1295

Thr Tyr Tyr Asn Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala

1300 1305 1310

Gly Leu Val Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Cys Cys Ser

1315 1320 1325

Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1330 1335

<210> 110

<211> 1341

<212> PRT

<213> artificial sequence

<220>

<223> PDI-MERS-H1cCT-AA

<400> 110

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Tyr Val Asp Val Gly Pro Asp Ser

20 25 30

Val Lys Ser Ala Cys Ile Glu Val Asp Ile Gln Gln Thr Phe Phe Asp

35 40 45

Lys Thr Trp Pro Arg Pro Ile Asp Val Ser Lys Ala Asp Gly Ile Ile

50 55 60

Tyr Pro Gln Gly Arg Thr Tyr Ser Asn Ile Thr Ile Thr Tyr Gln Gly

65 70 75 80

Leu Phe Pro Tyr Gln Gly Asp His Gly Asp Met Tyr Val Tyr Ser Ala

85 90 95

Gly His Ala Thr Gly Thr Thr Pro Gln Lys Leu Phe Val Ala Asn Tyr

100 105 110

Ser Gln Asp Val Lys Gln Phe Ala Asn Gly Phe Val Val Arg Ile Gly

115 120 125

Ala Ala Ala Asn Ser Thr Gly Thr Val Ile Ile Ser Pro Ser Thr Ser

130 135 140

Ala Thr Ile Arg Lys Ile Tyr Pro Ala Phe Met Leu Gly Ser Ser Val

145 150 155 160

Gly Asn Phe Ser Asp Gly Lys Met Gly Arg Phe Phe Asn His Thr Leu

165 170 175

Val Leu Leu Pro Asp Gly Cys Gly Thr Leu Leu Arg Ala Phe Tyr Cys

180 185 190

Ile Leu Glu Pro Arg Ser Gly Asn His Cys Pro Ala Gly Asn Ser Tyr

195 200 205

Thr Ser Phe Ala Thr Tyr His Thr Pro Ala Thr Asp Cys Ser Asp Gly

210 215 220

Asn Tyr Asn Arg Asn Ala Ser Leu Asn Ser Phe Lys Glu Tyr Phe Asn

225 230 235 240

Leu Arg Asn Cys Thr Phe Met Tyr Thr Tyr Asn Ile Thr Glu Asp Glu

245 250 255

Ile Leu Glu Trp Phe Gly Ile Thr Gln Thr Ala Gln Gly Val His Leu

260 265 270

Phe Ser Ser Arg Tyr Val Asp Leu Tyr Gly Gly Asn Met Phe Gln Phe

275 280 285

Ala Thr Leu Pro Val Tyr Asp Thr Ile Lys Tyr Tyr Ser Ile Ile Pro

290 295 300

His Ser Ile Arg Ser Ile Gln Ser Asp Arg Lys Ala Trp Ala Ala Phe

305 310 315 320

Tyr Val Tyr Lys Leu Gln Pro Leu Thr Phe Leu Leu Asp Phe Ser Val

325 330 335

Asp Gly Tyr Ile Arg Arg Ala Ile Asp Cys Gly Phe Asn Asp Leu Ser

340 345 350

Gln Leu His Cys Ser Tyr Glu Ser Phe Asp Val Glu Ser Gly Val Tyr

355 360 365

Ser Val Ser Ser Phe Glu Ala Lys Pro Ser Gly Ser Val Val Glu Gln

370 375 380

Ala Glu Gly Val Glu Cys Asp Phe Ser Pro Leu Leu Ser Gly Thr Pro

385 390 395 400

Pro Gln Val Tyr Asn Phe Lys Arg Leu Val Phe Thr Asn Cys Asn Tyr

405 410 415

Asn Leu Thr Lys Leu Leu Ser Leu Phe Ser Val Asn Asp Phe Thr Cys

420 425 430

Ser Gln Ile Ser Pro Ala Ala Ile Ala Ser Asn Cys Tyr Ser Ser Leu

435 440 445

Ile Leu Asp Tyr Phe Ser Tyr Pro Leu Ser Met Lys Ser Asp Leu Ser

450 455 460

Val Ser Ser Ala Gly Pro Ile Ser Gln Phe Asn Tyr Lys Gln Ser Phe

465 470 475 480

Ser Asn Pro Thr Cys Leu Ile Leu Ala Thr Val Pro His Asn Leu Thr

485 490 495

Thr Ile Thr Lys Pro Leu Lys Tyr Ser Tyr Ile Asn Lys Cys Ser Arg

500 505 510

Phe Leu Ser Asp Asp Arg Thr Glu Val Pro Gln Leu Val Asn Ala Asn

515 520 525

Gln Tyr Ser Pro Cys Val Ser Ile Val Pro Ser Thr Val Trp Glu Asp

530 535 540

Gly Asp Tyr Tyr Arg Lys Gln Leu Ser Pro Leu Glu Gly Gly Gly Trp

545 550 555 560

Leu Val Ala Ser Gly Ser Thr Val Ala Met Thr Glu Gln Leu Gln Met

565 570 575

Gly Phe Gly Ile Thr Val Gln Tyr Gly Thr Asp Thr Asn Ser Val Cys

580 585 590

Pro Lys Leu Glu Phe Ala Asn Asp Thr Lys Ile Ala Ser Gln Leu Gly

595 600 605

Asn Cys Val Glu Tyr Ser Leu Tyr Gly Val Ser Gly Arg Gly Val Phe

610 615 620

Gln Asn Cys Thr Ala Val Gly Val Arg Gln Gln Arg Phe Val Tyr Asp

625 630 635 640

Ala Tyr Gln Asn Leu Val Gly Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr

645 650 655

Cys Leu Arg Ala Cys Val Ser Val Pro Val Ser Val Ile Tyr Asp Lys

660 665 670

Glu Thr Lys Thr His Ala Thr Leu Phe Gly Ser Val Ala Cys Glu His

675 680 685

Ile Ser Ser Thr Met Ser Gln Tyr Ser Arg Ser Thr Arg Ser Met Leu

690 695 700

Lys Arg Arg Asp Ser Thr Tyr Gly Pro Leu Gln Thr Pro Val Gly Cys

705 710 715 720

Val Leu Gly Leu Val Asn Ser Ser Leu Phe Val Glu Asp Cys Lys Leu

725 730 735

Pro Leu Gly Gln Ser Leu Cys Ala Leu Pro Asp Thr Pro Ser Thr Leu

740 745 750

Thr Pro Ala Ser Val Gly Ser Val Pro Gly Glu Met Arg Leu Ala Ser

755 760 765

Ile Ala Phe Asn His Pro Ile Gln Val Asp Gln Leu Asn Ser Ser Tyr

770 775 780

Phe Lys Leu Ser Ile Pro Thr Asn Phe Ser Phe Gly Val Thr Gln Glu

785 790 795 800

Tyr Ile Gln Thr Thr Ile Gln Lys Val Thr Val Asp Cys Lys Gln Tyr

805 810 815

Val Cys Asn Gly Phe Gln Lys Cys Glu Gln Leu Leu Arg Glu Tyr Gly

820 825 830

Gln Phe Cys Ser Lys Ile Asn Gln Ala Leu His Gly Ala Asn Leu Arg

835 840 845

Gln Asp Asp Ser Val Arg Asn Leu Phe Ala Ser Val Lys Ser Ser Gln

850 855 860

Ser Ser Pro Ile Ile Pro Gly Phe Gly Gly Asp Phe Asn Leu Thr Leu

865 870 875 880

Leu Glu Pro Val Ser Ile Ser Thr Gly Ser Arg Ser Ala Arg Ser Ala

885 890 895

Ile Glu Asp Leu Leu Phe Asp Lys Val Thr Ile Ala Asp Pro Gly Tyr

900 905 910

Met Gln Gly Tyr Asp Asp Cys Met Gln Gln Gly Pro Ala Ser Ala Arg

915 920 925

Asp Leu Ile Cys Ala Gln Tyr Val Ala Gly Tyr Lys Val Leu Pro Pro

930 935 940

Leu Met Asp Val Asn Met Glu Ala Ala Tyr Thr Ser Ser Leu Leu Gly

945 950 955 960

Ser Ile Ala Gly Val Gly Trp Thr Ala Gly Leu Ser Ser Phe Ala Ala

965 970 975

Ile Pro Phe Ala Gln Ser Ile Phe Tyr Arg Leu Asn Gly Val Gly Ile

980 985 990

Thr Gln Gln Val Leu Ser Glu Asn Gln Lys Leu Ile Ala Asn Lys Phe

995 1000 1005

Asn Gln Ala Leu Gly Ala Met Gln Thr Gly Phe Thr Thr Thr Asn Glu

1010 1015 1020

Ala Phe His Lys Val Gln Asp Ala Val Asn Asn Asn Ala Gln Ala Leu

1025 1030 1035 1040

Ser Lys Leu Ala Ser Glu Leu Ser Asn Thr Phe Gly Ala Ile Ser Ala

1045 1050 1055

Ser Ile Gly Asp Ile Ile Gln Arg Leu Asp Pro Pro Glu Gln Asp Ala

1060 1065 1070

Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Thr Leu Asn Ala Phe

1075 1080 1085

Val Ala Gln Gln Leu Val Arg Ser Glu Ser Ala Ala Leu Ser Ala Gln

1090 1095 1100

Leu Ala Lys Asp Lys Val Asn Glu Cys Val Lys Ala Gln Ser Lys Arg

1105 1110 1115 1120

Ser Gly Phe Cys Gly Gln Gly Thr His Ile Val Ser Phe Val Val Asn

1125 1130 1135

Ala Pro Asn Gly Leu Tyr Phe Met His Val Gly Tyr Tyr Pro Ser Asn

1140 1145 1150

His Ile Glu Val Val Ser Ala Tyr Gly Leu Cys Asp Ala Ala Asn Pro

1155 1160 1165

Thr Asn Cys Ile Ala Pro Val Asn Gly Tyr Phe Ile Lys Thr Asn Asn

1170 1175 1180

Thr Arg Ile Val Asp Glu Trp Ser Tyr Thr Gly Ser Ser Phe Tyr Ala

1185 1190 1195 1200

Pro Glu Pro Ile Thr Ser Leu Asn Thr Lys Tyr Val Ala Pro Gln Val

1205 1210 1215

Thr Tyr Gln Asn Ile Ser Thr Asn Leu Pro Pro Pro Leu Leu Gly Asn

1220 1225 1230

Ser Thr Gly Ile Asp Phe Gln Asp Glu Leu Asp Glu Phe Phe Lys Asn

1235 1240 1245

Val Ser Thr Ser Ile Pro Asn Phe Gly Ser Leu Thr Gln Ile Asn Thr

1250 1255 1260

Thr Leu Leu Asp Leu Thr Tyr Glu Met Leu Ser Leu Gln Gln Val Val

1265 1270 1275 1280

Lys Ala Leu Asn Glu Ser Tyr Ile Asp Leu Lys Glu Leu Gly Asn Tyr

1285 1290 1295

Thr Tyr Tyr Asn Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala

1300 1305 1310

Gly Leu Val Ala Leu Ala Leu Cys Val Phe Phe Ile Leu Ser Phe Trp

1315 1320 1325

Met Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1330 1335 1340

<210> 111

<211> 4364

<212> DNA

<213> artificial sequence

<220>

<223> cloning vector 7147 from left to right T-DNA

<400> 111

tggcaggata tattgtggtg taaacaaatt gacgcttaga caacttaata acacattgcg 60

gacgttttta atgtactgaa ttaacgccga atcccgggct ggtatattta tatgttgtca 120

aataactcaa aaaccataaa agtttaagtt agcaagtgtg tacattttta cttgaacaaa 180

aatattcacc tactactgtt ataaatcatt attaaacatt agagtaaaga aatatggatg 240

ataagaacaa gagtagtgat attttgacaa caattttgtt gcaacatttg agaaaatttt 300

gttgttctct cttttcattg gtcaaaaaca atagagagag aaaaaggaag agggagaata 360

aaaacataat gtgagtatga gagagaaagt tgtacaaaag ttgtaccaaa atagttgtac 420

aaatatcatt gaggaatttg acaaaagcta cacaaataag ggttaattgc tgtaaataaa 480

taaggatgac gcattagaga gatgtaccat tagagaattt ttggcaagtc attaaaaaga 540

aagaataaat tatttttaaa attaaaagtt gagtcatttg attaaacatg tgattattta 600

atgaattgat gaaagagttg gattaaagtt gtattagtaa ttagaatttg gtgtcaaatt 660

taatttgaca tttgatcttt tcctatatat tgccccatag agtcagttaa ctcattttta 720

tatttcatag atcaaataag agaaataacg gtatattaat ccctccaaaa aaaaaaaacg 780

gtatatttac taaaaaatct aagccacgta ggaggataac aggatccccg taggaggata 840

acatccaatc caaccaatca caacaatcct gatgagataa cccactttaa gcccacgcat 900

ctgtggcaca tctacattat ctaaatcaca cattcttcca cacatctgag ccacacaaaa 960

accaatccac atctttatca cccattctat aaaaaatcac actttgtgag tctacacttt 1020

gattcccttc aaacacatac aaagagaaga gactaattaa ttaattaatc atcttgagag 1080

aaaatggaac gagctataca aggaaacgac gctagggaac aagctaacag tgaacgttgg 1140

gatggaggat caggaggtac cacttctccc ttcaaacttc ctgacgaaag tccgagttgg 1200

actgagtggc ggctacataa cgatgagacg aattcgaatc aagataatcc ccttggtttc 1260

aaggaaagct ggggtttcgg gaaagttgta tttaagagat atctcagata cgacaggacg 1320

gaagcttcac tgcacagagt ccttggatct tggacgggag attcggttaa ctatgcagca 1380

tctcgatttt tcggtttcga ccagatcgga tgtacctata gtattcggtt tcgaggagtt 1440

agtatcaccg tttctggagg gtcgcgaact cttcagcatc tctgtgagat ggcaattcgg 1500

tctaagcaag aactgctaca gcttgcccca atcgaagtgg aaagtaatgt atcaagagga 1560

tgccctgaag gtactcaaac cttcgaaaaa gaaagcgagt aagttaaaat gcttcttcgt 1620

ctcctattta taatatggtt tgttattgtt aattttgttc ttgtagaaga gcttaattaa 1680

tcgttgttgt tatgaaatac tatttgtatg agatgaactg gtgtaatgta attcatttac 1740

ataagtggag tcagaatcag aatgtttcct ccataactaa ctagacatga agacctgccg 1800

cgtacaattg tcttatattt gaacaactaa aattgaacat cttttgccac aactttataa 1860

gtggttaata tagctcaaat atatggtcaa gttcaataga ttaataatgg aaatatcagt 1920

tatcgaaatt cattaacaat caacttaacg ttattaacta ctaattttat atcatcccct 1980

ttgataaatg atagtacacc aattaggaag gagcatgctc gcctaggaga ttgtcgtttc 2040

ccgccttcag tttgcaagct gctctagccg tgtagccaat acgcaaaccg cctctccccg 2100

cgcgttggga attactagcg cgtgtcgaca agcttgcatg ccggtcaaca tggtggagca 2160

cgacacactt gtctactcca aaaatatcaa agatacagtc tcagaagacc aaagggcaat 2220

tgagactttt caacaaaggg taatatccgg aaacctcctc ggattccatt gcccagctat 2280

ctgtcacttt attgtgaaga tagtggaaaa ggaaggtggc tcctacaaat gccatcattg 2340

cgataaagga aaggccatcg ttgaagatgc ctctgccgac agtggtccca aagatggacc 2400

cccacccacg aggagcatcg tggaaaaaga agacgttcca accacgtctt caaagcaagt 2460

ggattgatgt gataacatgg tggagcacga cacacttgtc tactccaaaa atatcaaaga 2520

tacagtctca gaagaccaaa gggcaattga gacttttcaa caaagggtaa tatccggaaa 2580

cctcctcgga ttccattgcc cagctatctg tcactttatt gtgaagatag tggaaaagga 2640

aggtggctcc tacaaatgcc atcattgcga taaaggaaag gccatcgttg aagatgcctc 2700

tgccgacagt ggtcccaaag atggaccccc acccacgagg agcatcgtgg aaaaagaaga 2760

cgttccaacc acgtcttcaa agcaagtgga ttgatgtgat atctccactg acgtaaggga 2820

tgacgcacaa tcccactatc cttcgcaaga cccttcctct atataaggaa gttcatttca 2880

tttggagagg cactccattt gaatctatca aaccaaaaca cattgagacg tcacgtactc 2940

ctcagccaaa acgacacccc catctgtcta tccactggcc cctggatctg ctgcccaaac 3000

taactccatg gtgaccctgg gatgcctggt caagggctat ttccctgagc cagtgacagt 3060

gacctggaac tctggatccc tgtccagcgg tgtgcacacc ttcccagctg tcctgcagtc 3120

tgacctctac actctgagca gctcagtgac tgtcccctcc agcacctggc ccagcgagac 3180

cgtcacctgc aacgttgccc acccggccag cagcaccaag gtggacaaga aaattgtgcc 3240

cagggattgt ggttgtaagc cttgcatatg tacagtccca gaagtatcat ctgtcttcat 3300

cttcccccca aagcccaagg atgtgctcac cattactctg actcctaagg tcacgtgtgt 3360

tgtggtagac atcagcaagg atgatcccga ggtccagttc agctggtttg tagatgatgt 3420

ggaggtgcac acagctcaga cgcaaccccg ggaggagcag ttcaacagca ctttccgctc 3480

agtcagtgaa cttcccatca tgcaccagga ctggctcaat ggcaaggaga cgtccagatt 3540

ttggcgatct attcaactgt cgccagttca ttggtactgg tagtctccct gggggcaatc 3600

agtttctgga tgtgctctaa tgggtctcta cagtgtagaa tatgtattta aaggccttag 3660

tcgtgtcgtt tttcaaataa tataatcctt ttagggtttt agttagttta aattttctgt 3720

tgctcctgtt tagcaggtcg tgccttcagc aagcacacaa aaacagagtg tttattttaa 3780

gttgtttgtt tagtgattca aaaaaaaaat cgttcaaaca tttggcaata aagtttctta 3840

agattgaatc ctgttgccgg tcttgcgatg attatcatat aatttctgtt gaattacgtt 3900

aagcatgtaa taattaacat gtaatgcatg acgttattta tgagatgggt ttttatgatt 3960

agagtcccgc aattatacat ttaatacgcg atagaaaaca aaatatagcg cgcaaactag 4020

gataaattat cgcgcgcggt gtcatctatg ttactagatc tctagagtct caagcttggc 4080

gcgcccacgt gactagtggc actggccgtc gttttacaac gtcgtgactg ggaaaaccct 4140

ggcgttaccc aacttaatcg ccttgcagca catccccctt tcgccagctg gcgtaatagc 4200

gaagaggccc gcaccgatcg cccttcccaa cagttgcgca gcctgaatgg cgaatgctag 4260

agcagcttga gcttggatca gattgtcgtt tcccgccttc agtttaaact atcagtgttt 4320

gacaggatat attggcgggt aaacctaaga gaaaagagcg ttta 4364

<210> 112

<211> 1255

<212> PRT

<213> SARS-CoV-1

<400> 112

Met Phe Ile Phe Leu Leu Phe Leu Thr Leu Thr Ser Gly Ser Asp Leu

1 5 10 15

Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn Tyr Thr Gln

20 25 30

His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu Ile Phe Arg

35 40 45

Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro Phe Tyr Ser

50 55 60

Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Gly Asn Pro Val

65 70 75 80

Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu Lys Ser Asn

85 90 95

Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn Lys Ser Gln

100 105 110

Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile Arg Ala Cys

115 120 125

Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser Lys Pro Met

130 135 140

Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe Asn Cys Thr

145 150 155 160

Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser Glu Lys Ser

165 170 175

Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn Lys Asp Gly

180 185 190

Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val Val Arg Asp

195 200 205

Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys Leu Pro Leu

210 215 220

Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala Phe Ser Pro

225 230 235 240

Ala Gln Asp Ile Trp Gly Thr Ser Ala Ala Ala Tyr Phe Val Gly Tyr

245 250 255

Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn Gly Thr Ile

260 265 270

Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu Leu Lys Cys

275 280 285

Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln Thr Ser Asn

290 295 300

Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro Asn Ile Thr

305 310 315 320

Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys Phe Pro Ser

325 330 335

Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val Ala Asp Tyr

340 345 350

Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys Cys Tyr Gly

355 360 365

Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn Val Tyr Ala

370 375 380

Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile Ala Pro Gly

385 390 395 400

Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe

405 410 415

Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp Ala Thr Ser

420 425 430

Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His Gly Lys Leu

435 440 445

Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser Pro Asp Gly

450 455 460

Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro Leu Asn Asp

465 470 475 480

Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro Tyr Arg Val

485 490 495

Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr Val Cys Gly

500 505 510

Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val Asn Phe Asn

515 520 525

Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser Ser Lys Arg

530 535 540

Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp Phe Thr Asp

545 550 555 560

Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile Ser Pro Cys

565 570 575

Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Ala Ser Ser

580 585 590

Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp Val Ser Thr

595 600 605

Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile Tyr Ser Thr

610 615 620

Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile Gly Ala Glu

625 630 635 640

His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile

645 650 655

Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr Ser Gln Lys

660 665 670

Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser Ser Ile Ala

675 680 685

Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser Ile Ser Ile

690 695 700

Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser Val Asp Cys

705 710 715 720

Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn Leu Leu Leu

725 730 735

Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Ser Gly Ile

740 745 750

Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala Gln Val Lys

755 760 765

Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly Phe Asn Phe

770 775 780

Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg Ser Phe Ile

785 790 795 800

Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Met

805 810 815

Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg Asp Leu Ile

820 825 830

Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr

835 840 845

Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser Gly Thr Ala

850 855 860

Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe

865 870 875 880

Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn

885 890 895

Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe Asn Lys Ala

900 905 910

Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr Ala Leu Gly

915 920 925

Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu

930 935 940

Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn

945 950 955 960

Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp

965 970 975

Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln

980 985 990

Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala

995 1000 1005

Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe

1010 1015 1020

Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ala Ala Pro His

1025 1030 1035 1040

Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ser Gln Glu Arg Asn

1045 1050 1055

Phe Thr Thr Ala Pro Ala Ile Cys His Glu Gly Lys Ala Tyr Phe Pro

1060 1065 1070

Arg Glu Gly Val Phe Val Phe Asn Gly Thr Ser Trp Phe Ile Thr Gln

1075 1080 1085

Arg Asn Phe Phe Ser Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val

1090 1095 1100

Ser Gly Asn Cys Asp Val Val Ile Gly Ile Ile Asn Asn Thr Val Tyr

1105 1110 1115 1120

Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys

1125 1130 1135

Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser

1140 1145 1150

Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu

1155 1160 1165

Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu

1170 1175 1180

Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Val Trp Leu

1185 1190 1195 1200

Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Leu Leu

1205 1210 1215

Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala Cys Ser Cys

1220 1225 1230

Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys

1235 1240 1245

Gly Val Lys Leu His Tyr Thr

1250 1255

<210> 113

<211> 1353

<212> PRT

<213> MERS

<400> 113

Met Ile His Ser Val Phe Leu Leu Met Phe Leu Leu Thr Pro Thr Glu

1 5 10 15

Ser Tyr Val Asp Val Gly Pro Asp Ser Val Lys Ser Ala Cys Ile Glu

20 25 30

Val Asp Ile Gln Gln Thr Phe Phe Asp Lys Thr Trp Pro Arg Pro Ile

35 40 45

Asp Val Ser Lys Ala Asp Gly Ile Ile Tyr Pro Gln Gly Arg Thr Tyr

50 55 60

Ser Asn Ile Thr Ile Thr Tyr Gln Gly Leu Phe Pro Tyr Gln Gly Asp

65 70 75 80

His Gly Asp Met Tyr Val Tyr Ser Ala Gly His Ala Thr Gly Thr Thr

85 90 95

Pro Gln Lys Leu Phe Val Ala Asn Tyr Ser Gln Asp Val Lys Gln Phe

100 105 110

Ala Asn Gly Phe Val Val Arg Ile Gly Ala Ala Ala Asn Ser Thr Gly

115 120 125

Thr Val Ile Ile Ser Pro Ser Thr Ser Ala Thr Ile Arg Lys Ile Tyr

130 135 140

Pro Ala Phe Met Leu Gly Ser Ser Val Gly Asn Phe Ser Asp Gly Lys

145 150 155 160

Met Gly Arg Phe Phe Asn His Thr Leu Val Leu Leu Pro Asp Gly Cys

165 170 175

Gly Thr Leu Leu Arg Ala Phe Tyr Cys Ile Leu Glu Pro Arg Ser Gly

180 185 190

Asn His Cys Pro Ala Gly Asn Ser Tyr Thr Ser Phe Ala Thr Tyr His

195 200 205

Thr Pro Ala Thr Asp Cys Ser Asp Gly Asn Tyr Asn Arg Asn Ala Ser

210 215 220

Leu Asn Ser Phe Lys Glu Tyr Phe Asn Leu Arg Asn Cys Thr Phe Met

225 230 235 240

Tyr Thr Tyr Asn Ile Thr Glu Asp Glu Ile Leu Glu Trp Phe Gly Ile

245 250 255

Thr Gln Thr Ala Gln Gly Val His Leu Phe Ser Ser Arg Tyr Val Asp

260 265 270

Leu Tyr Gly Gly Asn Met Phe Gln Phe Ala Thr Leu Pro Val Tyr Asp

275 280 285

Thr Ile Lys Tyr Tyr Ser Ile Ile Pro His Ser Ile Arg Ser Ile Gln

290 295 300

Ser Asp Arg Lys Ala Trp Ala Ala Phe Tyr Val Tyr Lys Leu Gln Pro

305 310 315 320

Leu Thr Phe Leu Leu Asp Phe Ser Val Asp Gly Tyr Ile Arg Arg Ala

325 330 335

Ile Asp Cys Gly Phe Asn Asp Leu Ser Gln Leu His Cys Ser Tyr Glu

340 345 350

Ser Phe Asp Val Glu Ser Gly Val Tyr Ser Val Ser Ser Phe Glu Ala

355 360 365

Lys Pro Ser Gly Ser Val Val Glu Gln Ala Glu Gly Val Glu Cys Asp

370 375 380

Phe Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys

385 390 395 400

Arg Leu Val Phe Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser

405 410 415

Leu Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala

420 425 430

Ile Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr

435 440 445

Pro Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile

450 455 460

Ser Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile

465 470 475 480

Leu Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys

485 490 495

Tyr Ser Tyr Ile Asn Lys Cys Ser Arg Phe Leu Ser Asp Asp Arg Thr

500 505 510

Glu Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser

515 520 525

Ile Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln

530 535 540

Leu Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr

545 550 555 560

Val Ala Met Thr Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln

565 570 575

Tyr Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn

580 585 590

Asp Thr Lys Ile Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Leu

595 600 605

Tyr Gly Val Ser Gly Arg Gly Val Phe Gln Asn Cys Thr Ala Val Gly

610 615 620

Val Arg Gln Gln Arg Phe Val Tyr Asp Ala Tyr Gln Asn Leu Val Gly

625 630 635 640

Tyr Tyr Ser Asp Asp Gly Asn Tyr Tyr Cys Leu Arg Ala Cys Val Ser

645 650 655

Val Pro Val Ser Val Ile Tyr Asp Lys Glu Thr Lys Thr His Ala Thr

660 665 670

Leu Phe Gly Ser Val Ala Cys Glu His Ile Ser Ser Thr Met Ser Gln

675 680 685

Tyr Ser Arg Ser Thr Arg Ser Met Leu Lys Arg Arg Asp Ser Thr Tyr

690 695 700

Gly Pro Leu Gln Thr Pro Val Gly Cys Val Leu Gly Leu Val Asn Ser

705 710 715 720

Ser Leu Phe Val Glu Asp Cys Lys Leu Pro Leu Gly Gln Ser Leu Cys

725 730 735

Ala Leu Pro Asp Thr Pro Ser Thr Leu Thr Pro Arg Ser Val Arg Ser

740 745 750

Val Pro Gly Glu Met Arg Leu Ala Ser Ile Ala Phe Asn His Pro Ile

755 760 765

Gln Val Asp Gln Leu Asn Ser Ser Tyr Phe Lys Leu Ser Ile Pro Thr

770 775 780

Asn Phe Ser Phe Gly Val Thr Gln Glu Tyr Ile Gln Thr Thr Ile Gln

785 790 795 800

Lys Val Thr Val Asp Cys Lys Gln Tyr Val Cys Asn Gly Phe Gln Lys

805 810 815

Cys Glu Gln Leu Leu Arg Glu Tyr Gly Gln Phe Cys Ser Lys Ile Asn

820 825 830

Gln Ala Leu His Gly Ala Asn Leu Arg Gln Asp Asp Ser Val Arg Asn

835 840 845

Leu Phe Ala Ser Val Lys Ser Ser Gln Ser Ser Pro Ile Ile Pro Gly

850 855 860

Phe Gly Gly Asp Phe Asn Leu Thr Leu Leu Glu Pro Val Ser Ile Ser

865 870 875 880

Thr Gly Ser Arg Ser Ala Arg Ser Ala Ile Glu Asp Leu Leu Phe Asp

885 890 895

Lys Val Thr Ile Ala Asp Pro Gly Tyr Met Gln Gly Tyr Asp Asp Cys

900 905 910

Met Gln Gln Gly Pro Ala Ser Ala Arg Asp Leu Ile Cys Ala Gln Tyr

915 920 925

Val Ala Gly Tyr Lys Val Leu Pro Pro Leu Met Asp Val Asn Met Glu

930 935 940

Ala Ala Tyr Thr Ser Ser Leu Leu Gly Ser Ile Ala Gly Val Gly Trp

945 950 955 960

Thr Ala Gly Leu Ser Ser Phe Ala Ala Ile Pro Phe Ala Gln Ser Ile

965 970 975

Phe Tyr Arg Leu Asn Gly Val Gly Ile Thr Gln Gln Val Leu Ser Glu

980 985 990

Asn Gln Lys Leu Ile Ala Asn Lys Phe Asn Gln Ala Leu Gly Ala Met

995 1000 1005

Gln Thr Gly Phe Thr Thr Thr Asn Glu Ala Phe His Lys Val Gln Asp

1010 1015 1020

Ala Val Asn Asn Asn Ala Gln Ala Leu Ser Lys Leu Ala Ser Glu Leu

1025 1030 1035 1040

Ser Asn Thr Phe Gly Ala Ile Ser Ala Ser Ile Gly Asp Ile Ile Gln

1045 1050 1055

Arg Leu Asp Val Leu Glu Gln Asp Ala Gln Ile Asp Arg Leu Ile Asn

1060 1065 1070

Gly Arg Leu Thr Thr Leu Asn Ala Phe Val Ala Gln Gln Leu Val Arg

1075 1080 1085

Ser Glu Ser Ala Ala Leu Ser Ala Gln Leu Ala Lys Asp Lys Val Asn

1090 1095 1100

Glu Cys Val Lys Ala Gln Ser Lys Arg Ser Gly Phe Cys Gly Gln Gly

1105 1110 1115 1120

Thr His Ile Val Ser Phe Val Val Asn Ala Pro Asn Gly Leu Tyr Phe

1125 1130 1135

Met His Val Gly Tyr Tyr Pro Ser Asn His Ile Glu Val Val Ser Ala

1140 1145 1150

Tyr Gly Leu Cys Asp Ala Ala Asn Pro Thr Asn Cys Ile Ala Pro Val

1155 1160 1165

Asn Gly Tyr Phe Ile Lys Thr Asn Asn Thr Arg Ile Val Asp Glu Trp

1170 1175 1180

Ser Tyr Thr Gly Ser Ser Phe Tyr Ala Pro Glu Pro Ile Thr Ser Leu

1185 1190 1195 1200

Asn Thr Lys Tyr Val Ala Pro Gln Val Thr Tyr Gln Asn Ile Ser Thr

1205 1210 1215

Asn Leu Pro Pro Pro Leu Leu Gly Asn Ser Thr Gly Ile Asp Phe Gln

1220 1225 1230

Asp Glu Leu Asp Glu Phe Phe Lys Asn Val Ser Thr Ser Ile Pro Asn

1235 1240 1245

Phe Gly Ser Leu Thr Gln Ile Asn Thr Thr Leu Leu Asp Leu Thr Tyr

1250 1255 1260

Glu Met Leu Ser Leu Gln Gln Val Val Lys Ala Leu Asn Glu Ser Tyr

1265 1270 1275 1280

Ile Asp Leu Lys Glu Leu Gly Asn Tyr Thr Tyr Tyr Asn Lys Trp Pro

1285 1290 1295

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1300 1305 1310

Cys Val Phe Phe Ile Leu Cys Cys Thr Gly Cys Gly Thr Asn Cys Met

1315 1320 1325

Gly Lys Leu Lys Cys Asn Arg Cys Cys Asp Arg Tyr Glu Glu Tyr Asp

1330 1335 1340

Leu Glu Pro His Lys Val His Val His

1345 1350

<210> 114

<211> 1242

<212> PRT

<213> SARS-CoV-1

<400> 114

Ser Asp Leu Asp Arg Cys Thr Thr Phe Asp Asp Val Gln Ala Pro Asn

1 5 10 15

Tyr Thr Gln His Thr Ser Ser Met Arg Gly Val Tyr Tyr Pro Asp Glu

20 25 30

Ile Phe Arg Ser Asp Thr Leu Tyr Leu Thr Gln Asp Leu Phe Leu Pro

35 40 45

Phe Tyr Ser Asn Val Thr Gly Phe His Thr Ile Asn His Thr Phe Gly

50 55 60

Asn Pro Val Ile Pro Phe Lys Asp Gly Ile Tyr Phe Ala Ala Thr Glu

65 70 75 80

Lys Ser Asn Val Val Arg Gly Trp Val Phe Gly Ser Thr Met Asn Asn

85 90 95

Lys Ser Gln Ser Val Ile Ile Ile Asn Asn Ser Thr Asn Val Val Ile

100 105 110

Arg Ala Cys Asn Phe Glu Leu Cys Asp Asn Pro Phe Phe Ala Val Ser

115 120 125

Lys Pro Met Gly Thr Gln Thr His Thr Met Ile Phe Asp Asn Ala Phe

130 135 140

Asn Cys Thr Phe Glu Tyr Ile Ser Asp Ala Phe Ser Leu Asp Val Ser

145 150 155 160

Glu Lys Ser Gly Asn Phe Lys His Leu Arg Glu Phe Val Phe Lys Asn

165 170 175

Lys Asp Gly Phe Leu Tyr Val Tyr Lys Gly Tyr Gln Pro Ile Asp Val

180 185 190

Val Arg Asp Leu Pro Ser Gly Phe Asn Thr Leu Lys Pro Ile Phe Lys

195 200 205

Leu Pro Leu Gly Ile Asn Ile Thr Asn Phe Arg Ala Ile Leu Thr Ala

210 215 220

Phe Ser Pro Ala Gln Asp Ile Trp Gly Thr Ser Ala Ala Ala Tyr Phe

225 230 235 240

Val Gly Tyr Leu Lys Pro Thr Thr Phe Met Leu Lys Tyr Asp Glu Asn

245 250 255

Gly Thr Ile Thr Asp Ala Val Asp Cys Ser Gln Asn Pro Leu Ala Glu

260 265 270

Leu Lys Cys Ser Val Lys Ser Phe Glu Ile Asp Lys Gly Ile Tyr Gln

275 280 285

Thr Ser Asn Phe Arg Val Val Pro Ser Gly Asp Val Val Arg Phe Pro

290 295 300

Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Lys

305 310 315 320

Phe Pro Ser Val Tyr Ala Trp Glu Arg Lys Lys Ile Ser Asn Cys Val

325 330 335

Ala Asp Tyr Ser Val Leu Tyr Asn Ser Thr Phe Phe Ser Thr Phe Lys

340 345 350

Cys Tyr Gly Val Ser Ala Thr Lys Leu Asn Asp Leu Cys Phe Ser Asn

355 360 365

Val Tyr Ala Asp Ser Phe Val Val Lys Gly Asp Asp Val Arg Gln Ile

370 375 380

Ala Pro Gly Gln Thr Gly Val Ile Ala Asp Tyr Asn Tyr Lys Leu Pro

385 390 395 400

Asp Asp Phe Met Gly Cys Val Leu Ala Trp Asn Thr Arg Asn Ile Asp

405 410 415

Ala Thr Ser Thr Gly Asn Tyr Asn Tyr Lys Tyr Arg Tyr Leu Arg His

420 425 430

Gly Lys Leu Arg Pro Phe Glu Arg Asp Ile Ser Asn Val Pro Phe Ser

435 440 445

Pro Asp Gly Lys Pro Cys Thr Pro Pro Ala Leu Asn Cys Tyr Trp Pro

450 455 460

Leu Asn Asp Tyr Gly Phe Tyr Thr Thr Thr Gly Ile Gly Tyr Gln Pro

465 470 475 480

Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu Asn Ala Pro Ala Thr

485 490 495

Val Cys Gly Pro Lys Leu Ser Thr Asp Leu Ile Lys Asn Gln Cys Val

500 505 510

Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Pro Ser

515 520 525

Ser Lys Arg Phe Gln Pro Phe Gln Gln Phe Gly Arg Asp Val Ser Asp

530 535 540

Phe Thr Asp Ser Val Arg Asp Pro Lys Thr Ser Glu Ile Leu Asp Ile

545 550 555 560

Ser Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn

565 570 575

Ala Ser Ser Glu Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Asp

580 585 590

Val Ser Thr Ala Ile His Ala Asp Gln Leu Thr Pro Ala Trp Arg Ile

595 600 605

Tyr Ser Thr Gly Asn Asn Val Phe Gln Thr Gln Ala Gly Cys Leu Ile

610 615 620

Gly Ala Glu His Val Asp Thr Ser Tyr Glu Cys Asp Ile Pro Ile Gly

625 630 635 640

Ala Gly Ile Cys Ala Ser Tyr His Thr Val Ser Leu Leu Arg Ser Thr

645 650 655

Ser Gln Lys Ser Ile Val Ala Tyr Thr Met Ser Leu Gly Ala Asp Ser

660 665 670

Ser Ile Ala Tyr Ser Asn Asn Thr Ile Ala Ile Pro Thr Asn Phe Ser

675 680 685

Ile Ser Ile Thr Thr Glu Val Met Pro Val Ser Met Ala Lys Thr Ser

690 695 700

Val Asp Cys Asn Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ala Asn

705 710 715 720

Leu Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu

725 730 735

Ser Gly Ile Ala Ala Glu Gln Asp Arg Asn Thr Arg Glu Val Phe Ala

740 745 750

Gln Val Lys Gln Met Tyr Lys Thr Pro Thr Leu Lys Tyr Phe Gly Gly

755 760 765

Phe Asn Phe Ser Gln Ile Leu Pro Asp Pro Leu Lys Pro Thr Lys Arg

770 775 780

Ser Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala

785 790 795 800

Gly Phe Met Lys Gln Tyr Gly Glu Cys Leu Gly Asp Ile Asn Ala Arg

805 810 815

Asp Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro

820 825 830

Leu Leu Thr Asp Asp Met Ile Ala Ala Tyr Thr Ala Ala Leu Val Ser

835 840 845

Gly Thr Ala Thr Ala Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln

850 855 860

Ile Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val

865 870 875 880

Thr Gln Asn Val Leu Tyr Glu Asn Gln Lys Gln Ile Ala Asn Gln Phe

885 890 895

Asn Lys Ala Ile Ser Gln Ile Gln Glu Ser Leu Thr Thr Thr Ser Thr

900 905 910

Ala Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu

915 920 925

Asn Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser

930 935 940

Val Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val

945 950 955 960

Gln Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr

965 970 975

Val Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn

980 985 990

Leu Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg

995 1000 1005

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ala

1010 1015 1020

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ser Gln

1025 1030 1035 1040

Glu Arg Asn Phe Thr Thr Ala Pro Ala Ile Cys His Glu Gly Lys Ala

1045 1050 1055

Tyr Phe Pro Arg Glu Gly Val Phe Val Phe Asn Gly Thr Ser Trp Phe

1060 1065 1070

Ile Thr Gln Arg Asn Phe Phe Ser Pro Gln Ile Ile Thr Thr Asp Asn

1075 1080 1085

Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Ile Asn Asn

1090 1095 1100

Thr Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu

1105 1110 1115 1120

Leu Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly

1125 1130 1135

Asp Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile

1140 1145 1150

Asp Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp

1155 1160 1165

Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr

1170 1175 1180

Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr

1185 1190 1195 1200

Ile Leu Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Ala

1205 1210 1215

Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro

1220 1225 1230

Val Leu Lys Gly Val Lys Leu His Tyr Thr

1235 1240

<210> 115

<211> 1336

<212> PRT

<213> MERS

<400> 115

Tyr Val Asp Val Gly Pro Asp Ser Val Lys Ser Ala Cys Ile Glu Val

1 5 10 15

Asp Ile Gln Gln Thr Phe Phe Asp Lys Thr Trp Pro Arg Pro Ile Asp

20 25 30

Val Ser Lys Ala Asp Gly Ile Ile Tyr Pro Gln Gly Arg Thr Tyr Ser

35 40 45

Asn Ile Thr Ile Thr Tyr Gln Gly Leu Phe Pro Tyr Gln Gly Asp His

50 55 60

Gly Asp Met Tyr Val Tyr Ser Ala Gly His Ala Thr Gly Thr Thr Pro

65 70 75 80

Gln Lys Leu Phe Val Ala Asn Tyr Ser Gln Asp Val Lys Gln Phe Ala

85 90 95

Asn Gly Phe Val Val Arg Ile Gly Ala Ala Ala Asn Ser Thr Gly Thr

100 105 110

Val Ile Ile Ser Pro Ser Thr Ser Ala Thr Ile Arg Lys Ile Tyr Pro

115 120 125

Ala Phe Met Leu Gly Ser Ser Val Gly Asn Phe Ser Asp Gly Lys Met

130 135 140

Gly Arg Phe Phe Asn His Thr Leu Val Leu Leu Pro Asp Gly Cys Gly

145 150 155 160

Thr Leu Leu Arg Ala Phe Tyr Cys Ile Leu Glu Pro Arg Ser Gly Asn

165 170 175

His Cys Pro Ala Gly Asn Ser Tyr Thr Ser Phe Ala Thr Tyr His Thr

180 185 190

Pro Ala Thr Asp Cys Ser Asp Gly Asn Tyr Asn Arg Asn Ala Ser Leu

195 200 205

Asn Ser Phe Lys Glu Tyr Phe Asn Leu Arg Asn Cys Thr Phe Met Tyr

210 215 220

Thr Tyr Asn Ile Thr Glu Asp Glu Ile Leu Glu Trp Phe Gly Ile Thr

225 230 235 240

Gln Thr Ala Gln Gly Val His Leu Phe Ser Ser Arg Tyr Val Asp Leu

245 250 255

Tyr Gly Gly Asn Met Phe Gln Phe Ala Thr Leu Pro Val Tyr Asp Thr

260 265 270

Ile Lys Tyr Tyr Ser Ile Ile Pro His Ser Ile Arg Ser Ile Gln Ser

275 280 285

Asp Arg Lys Ala Trp Ala Ala Phe Tyr Val Tyr Lys Leu Gln Pro Leu

290 295 300

Thr Phe Leu Leu Asp Phe Ser Val Asp Gly Tyr Ile Arg Arg Ala Ile

305 310 315 320

Asp Cys Gly Phe Asn Asp Leu Ser Gln Leu His Cys Ser Tyr Glu Ser

325 330 335

Phe Asp Val Glu Ser Gly Val Tyr Ser Val Ser Ser Phe Glu Ala Lys

340 345 350

Pro Ser Gly Ser Val Val Glu Gln Ala Glu Gly Val Glu Cys Asp Phe

355 360 365

Ser Pro Leu Leu Ser Gly Thr Pro Pro Gln Val Tyr Asn Phe Lys Arg

370 375 380

Leu Val Phe Thr Asn Cys Asn Tyr Asn Leu Thr Lys Leu Leu Ser Leu

385 390 395 400

Phe Ser Val Asn Asp Phe Thr Cys Ser Gln Ile Ser Pro Ala Ala Ile

405 410 415

Ala Ser Asn Cys Tyr Ser Ser Leu Ile Leu Asp Tyr Phe Ser Tyr Pro

420 425 430

Leu Ser Met Lys Ser Asp Leu Ser Val Ser Ser Ala Gly Pro Ile Ser

435 440 445

Gln Phe Asn Tyr Lys Gln Ser Phe Ser Asn Pro Thr Cys Leu Ile Leu

450 455 460

Ala Thr Val Pro His Asn Leu Thr Thr Ile Thr Lys Pro Leu Lys Tyr

465 470 475 480

Ser Tyr Ile Asn Lys Cys Ser Arg Phe Leu Ser Asp Asp Arg Thr Glu

485 490 495

Val Pro Gln Leu Val Asn Ala Asn Gln Tyr Ser Pro Cys Val Ser Ile

500 505 510

Val Pro Ser Thr Val Trp Glu Asp Gly Asp Tyr Tyr Arg Lys Gln Leu

515 520 525

Ser Pro Leu Glu Gly Gly Gly Trp Leu Val Ala Ser Gly Ser Thr Val

530 535 540

Ala Met Thr Glu Gln Leu Gln Met Gly Phe Gly Ile Thr Val Gln Tyr

545 550 555 560

Gly Thr Asp Thr Asn Ser Val Cys Pro Lys Leu Glu Phe Ala Asn Asp

565 570 575

Thr Lys Ile Ala Ser Gln Leu Gly Asn Cys Val Glu Tyr Ser Leu Tyr

580 585 590

Gly Val Ser Gly Arg Gly Val Phe Gln Asn Cys Thr Ala Val Gly Val

595 600 605

Arg Gln Gln Arg Phe Val Tyr Asp Ala Tyr Gln Asn Leu Val Gly Tyr

610 615 620

Tyr Ser Asp Asp Gly Asn Tyr Tyr Cys Leu Arg Ala Cys Val Ser Val

625 630 635 640

Pro Val Ser Val Ile Tyr Asp Lys Glu Thr Lys Thr His Ala Thr Leu

645 650 655

Phe Gly Ser Val Ala Cys Glu His Ile Ser Ser Thr Met Ser Gln Tyr

660 665 670

Ser Arg Ser Thr Arg Ser Met Leu Lys Arg Arg Asp Ser Thr Tyr Gly

675 680 685

Pro Leu Gln Thr Pro Val Gly Cys Val Leu Gly Leu Val Asn Ser Ser

690 695 700

Leu Phe Val Glu Asp Cys Lys Leu Pro Leu Gly Gln Ser Leu Cys Ala

705 710 715 720

Leu Pro Asp Thr Pro Ser Thr Leu Thr Pro Arg Ser Val Arg Ser Val

725 730 735

Pro Gly Glu Met Arg Leu Ala Ser Ile Ala Phe Asn His Pro Ile Gln

740 745 750

Val Asp Gln Leu Asn Ser Ser Tyr Phe Lys Leu Ser Ile Pro Thr Asn

755 760 765

Phe Ser Phe Gly Val Thr Gln Glu Tyr Ile Gln Thr Thr Ile Gln Lys

770 775 780

Val Thr Val Asp Cys Lys Gln Tyr Val Cys Asn Gly Phe Gln Lys Cys

785 790 795 800

Glu Gln Leu Leu Arg Glu Tyr Gly Gln Phe Cys Ser Lys Ile Asn Gln

805 810 815

Ala Leu His Gly Ala Asn Leu Arg Gln Asp Asp Ser Val Arg Asn Leu

820 825 830

Phe Ala Ser Val Lys Ser Ser Gln Ser Ser Pro Ile Ile Pro Gly Phe

835 840 845

Gly Gly Asp Phe Asn Leu Thr Leu Leu Glu Pro Val Ser Ile Ser Thr

850 855 860

Gly Ser Arg Ser Ala Arg Ser Ala Ile Glu Asp Leu Leu Phe Asp Lys

865 870 875 880

Val Thr Ile Ala Asp Pro Gly Tyr Met Gln Gly Tyr Asp Asp Cys Met

885 890 895

Gln Gln Gly Pro Ala Ser Ala Arg Asp Leu Ile Cys Ala Gln Tyr Val

900 905 910

Ala Gly Tyr Lys Val Leu Pro Pro Leu Met Asp Val Asn Met Glu Ala

915 920 925

Ala Tyr Thr Ser Ser Leu Leu Gly Ser Ile Ala Gly Val Gly Trp Thr

930 935 940

Ala Gly Leu Ser Ser Phe Ala Ala Ile Pro Phe Ala Gln Ser Ile Phe

945 950 955 960

Tyr Arg Leu Asn Gly Val Gly Ile Thr Gln Gln Val Leu Ser Glu Asn

965 970 975

Gln Lys Leu Ile Ala Asn Lys Phe Asn Gln Ala Leu Gly Ala Met Gln

980 985 990

Thr Gly Phe Thr Thr Thr Asn Glu Ala Phe His Lys Val Gln Asp Ala

995 1000 1005

Val Asn Asn Asn Ala Gln Ala Leu Ser Lys Leu Ala Ser Glu Leu Ser

1010 1015 1020

Asn Thr Phe Gly Ala Ile Ser Ala Ser Ile Gly Asp Ile Ile Gln Arg

1025 1030 1035 1040

Leu Asp Val Leu Glu Gln Asp Ala Gln Ile Asp Arg Leu Ile Asn Gly

1045 1050 1055

Arg Leu Thr Thr Leu Asn Ala Phe Val Ala Gln Gln Leu Val Arg Ser

1060 1065 1070

Glu Ser Ala Ala Leu Ser Ala Gln Leu Ala Lys Asp Lys Val Asn Glu

1075 1080 1085

Cys Val Lys Ala Gln Ser Lys Arg Ser Gly Phe Cys Gly Gln Gly Thr

1090 1095 1100

His Ile Val Ser Phe Val Val Asn Ala Pro Asn Gly Leu Tyr Phe Met

1105 1110 1115 1120

His Val Gly Tyr Tyr Pro Ser Asn His Ile Glu Val Val Ser Ala Tyr

1125 1130 1135

Gly Leu Cys Asp Ala Ala Asn Pro Thr Asn Cys Ile Ala Pro Val Asn

1140 1145 1150

Gly Tyr Phe Ile Lys Thr Asn Asn Thr Arg Ile Val Asp Glu Trp Ser

1155 1160 1165

Tyr Thr Gly Ser Ser Phe Tyr Ala Pro Glu Pro Ile Thr Ser Leu Asn

1170 1175 1180

Thr Lys Tyr Val Ala Pro Gln Val Thr Tyr Gln Asn Ile Ser Thr Asn

1185 1190 1195 1200

Leu Pro Pro Pro Leu Leu Gly Asn Ser Thr Gly Ile Asp Phe Gln Asp

1205 1210 1215

Glu Leu Asp Glu Phe Phe Lys Asn Val Ser Thr Ser Ile Pro Asn Phe

1220 1225 1230

Gly Ser Leu Thr Gln Ile Asn Thr Thr Leu Leu Asp Leu Thr Tyr Glu

1235 1240 1245

Met Leu Ser Leu Gln Gln Val Val Lys Ala Leu Asn Glu Ser Tyr Ile

1250 1255 1260

Asp Leu Lys Glu Leu Gly Asn Tyr Thr Tyr Tyr Asn Lys Trp Pro Trp

1265 1270 1275 1280

Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu Cys

1285 1290 1295

Val Phe Phe Ile Leu Cys Cys Thr Gly Cys Gly Thr Asn Cys Met Gly

1300 1305 1310

Lys Leu Lys Cys Asn Arg Cys Cys Asp Arg Tyr Glu Glu Tyr Asp Leu

1315 1320 1325

Glu Pro His Lys Val His Val His

1330 1335

<210> 116

<211> 60

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-SARS-COV-1 wtTMCT-AA

<400> 116

Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Leu Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys

20 25 30

Gly Ala Cys Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser

35 40 45

Glu Pro Val Leu Lys Gly Val Lys Leu His Tyr Thr

50 55 60

<210> 117

<211> 40

<212> PRT

<213> artificial sequence

<220>

<223> YQILSIYSTVASSLALAIMMAGLSLWMCSNGSLQCRICI

<400> 117

Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala

1 5 10 15

Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

20 25 30

Ser Leu Gln Cys Arg Ile Cys Ile

35 40

<210> 118

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-SARS-COV-1H 5iCT-AA

<400> 118

Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Leu Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 119

<211> 34

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-SARS-COV-1H 5iCT (V4) -AA

<400> 119

Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Leu Leu Cys Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

20 25 30

Cys Ile

<210> 120

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-SARS-COV-1H 1cCT-AA

<400> 120

Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Leu Leu Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 121

<211> 57

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-MERS-wtTMCT-AA

<400> 121

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1 5 10 15

Cys Val Phe Phe Ile Leu Cys Cys Thr Gly Cys Gly Thr Asn Cys Met

20 25 30

Gly Lys Leu Lys Cys Asn Arg Cys Cys Asp Arg Tyr Glu Glu Tyr Asp

35 40 45

Leu Glu Pro His Lys Val His Val His

50 55

<210> 122

<211> 40

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-MERS-H5iTMCT-AA

<400> 122

Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala

1 5 10 15

Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

20 25 30

Ser Leu Gln Cys Arg Ile Cys Ile

35 40

<210> 123

<211> 38

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-MERS-H5iCT-AA

<400> 123

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1 5 10 15

Cys Val Phe Phe Ile Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu

20 25 30

Gln Cys Arg Ile Cys Ile

35

<210> 124

<211> 35

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-MERS-H5iCT (V4) -AA

<400> 124

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1 5 10 15

Cys Val Phe Phe Ile Leu Cys Cys Ser Asn Gly Ser Leu Gln Cys Arg

20 25 30

Ile Cys Ile

35

<210> 125

<211> 38

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-MERS-H1cCT-AA

<400> 125

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1 5 10 15

Cys Val Phe Phe Ile Leu Ser Phe Trp Met Cys Ser Asn Gly Ser Leu

20 25 30

Gln Cys Arg Ile Cys Ile

35

<210> 126

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein+H2 Cal

<400> 126

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 127

<211> 36

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein+H2 Minn

<400> 127

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Met Trp Ala Cys Gln Lys Gly Asn Ile Arg Cys

20 25 30

Asn Ile Cys Ile

35

<210> 128

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein+H2HK

<400> 128

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Gly Leu Trp Met Cys Ser Asn Gly Ser Met Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 129

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein +H27 Guangdong

<400> 129

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Val Phe Ile Cys Val Lys Asn Gly Asn Met Arg

20 25 30

Cys Thr Ile Cys Ile

35

<210> 130

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein+H2HK

<400> 130

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Leu Phe Trp Ala Met Ser Asn Gly Ser Cys Arg

20 25 30

Cys Asn Ile Cys Ile

35

<210> 131

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-S-protein+B/Wash

<400> 131

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Met Leu Val Val Tyr Met Val Ser Arg Asp Asn Val Ser

20 25 30

Cys Ser Ile Cys Leu

35

<210> 132

<211> 22

<212> PRT

<213> artificial sequence

<220>

<223> consensus sequence of TM Domain of coronavirus S-protein

<220>

<221> misc_feature

<222> (3)..(3)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (12)..(12)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (14)..(16)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> MISC_FEATURE

<222> (17)..(17)

<223> Xaa may or may not be present

<220>

<221> misc_feature

<222> (19)..(21)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (3)..(3)

<223> The 'Xaa' at location 3 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (12)..(12)

<223> The 'Xaa' at location 12 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (14)..(14)

<223> The 'Xaa' at location 14 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (15)..(15)

<223> The 'Xaa' at location 15 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (16)..(16)

<223> The 'Xaa' at location 16 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (17)..(17)

<223> The 'Xaa' at location 17 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (19)..(19)

<223> The 'Xaa' at location 19 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (20)..(20)

<223> The 'Xaa' at location 20 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (21)..(21)

<223> The 'Xaa' at location 21 stands for Gln, Arg, Pro, or Leu.

<400> 132

Trp Tyr Xaa Trp Leu Gly Phe Ile Ala Gly Leu Xaa Ala Xaa Xaa Xaa

1 5 10 15

Xaa Val Xaa Xaa Xaa Leu

20

<210> 133

<211> 22

<212> PRT

<213> artificial sequence

<220>

<223> consensus sequence of TM Domain of coronavirus S-protein

<220>

<221> MISC_FEATURE

<222> (3)..(3)

<223> Xaa may be Ile or Val

<220>

<221> MISC_FEATURE

<222> (12)..(12)

<223> Xaa may be Val or Ile

<220>

<221> MISC_FEATURE

<222> (14)..(14)

<223> Xaa may be Leu or Ile

<220>

<221> MISC_FEATURE

<222> (15)..(15)

<223> Xaa may be Ala or Val

<220>

<221> MISC_FEATURE

<222> (16)..(16)

<223> Xaa may be Leu or Met

<220>

<221> MISC_FEATURE

<222> (17)..(17)

<223> Xaa may be Cys or absent

<220>

<221> MISC_FEATURE

<222> (19)..(19)

<223> Xaa may be Phe or Thr

<220>

<221> MISC_FEATURE

<222> (20)..(20)

<223> Xaa may be Phe or Ile

<220>

<221> misc_feature

<222> (21)..(21)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (3)..(3)

<223> The 'Xaa' at location 3 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (12)..(12)

<223> The 'Xaa' at location 12 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (14)..(14)

<223> The 'Xaa' at location 14 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (15)..(15)

<223> The 'Xaa' at location 15 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (16)..(16)

<223> The 'Xaa' at location 16 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (17)..(17)

<223> The 'Xaa' at location 17 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (19)..(19)

<223> The 'Xaa' at location 19 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (20)..(20)

<223> The 'Xaa' at location 20 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (21)..(21)

<223> The 'Xaa' at location 21 stands for Gln, Arg, Pro, or Leu.

<400> 133

Trp Tyr Xaa Trp Leu Gly Phe Ile Ala Gly Leu Xaa Ala Xaa Xaa Xaa

1 5 10 15

Xaa Val Xaa Xaa Xaa Leu

20

<210> 134

<211> 33

<212> PRT

<213> artificial sequence

<220>

<223> modified SARS-CoV-1S protein, TM/CT region having intermediate peptide sequence

<220>

<221> MISC_FEATURE

<222> (21)..(21)

<223> X may be any combination of 0 to 10 amino acids.

<220>

<221> misc_feature

<222> (27)..(28)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (30)..(30)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (21)..(21)

<223> The 'Xaa' at location 21 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (27)..(27)

<223> The 'Xaa' at location 27 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (28)..(28)

<223> The 'Xaa' at location 28 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (30)..(30)

<223> The 'Xaa' at location 30 stands for Gln, Arg, Pro, or Leu.

<400> 134

Trp Tyr Val Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met

1 5 10 15

Val Thr Ile Leu Xaa Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile Cys

20 25 30

Ile

<210> 135

<211> 35

<212> PRT

<213> artificial sequence

<220>

<223> modified MERS S protein, TM/CT region with intermediate peptide sequence

<220>

<221> MISC_FEATURE

<222> (23)..(23)

<223> X may be any combination of 0 to 10 amino acids

<220>

<221> misc_feature

<222> (29)..(30)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (32)..(32)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (23)..(23)

<223> The 'Xaa' at location 23 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (29)..(29)

<223> The 'Xaa' at location 29 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (30)..(30)

<223> The 'Xaa' at location 30 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (32)..(32)

<223> The 'Xaa' at location 32 stands for Gln, Arg, Pro, or Leu.

<400> 135

Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly Leu Val Ala Leu Ala Leu

1 5 10 15

Cys Val Phe Phe Ile Leu Xaa Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa

20 25 30

Ile Cys Ile

35

<210> 136

<211> 49

<212> DNA

<213> artificial sequence

<220>

<223> IF(AvB+wtCT-OC43).r

<400> 136

acgacacgac taaggccttc agtcgtcatg cgaggtctta atgacaagc 49

<210> 137

<211> 4113

<212> DNA

<213> artificial sequence

<220>

<223> PDI-OC43-wtTMCT-DNA

<400> 137

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgatcgg cgatctgaat tgtaccctgg atccccgcct gaaagggagc 120

tttaacaacc gagatacagg acccccgtct atatccatag atacagtgga tgttacgaac 180

gggctcggca cctactatgt gctagaccga gtttatttga acaccacctt attcctcaat 240

ggatactacc caacttcagg tagtacttac agaaacatgg cgctgaaggg tacggatctg 300

ctgagcaccc tatggtttaa acctcccttc ctctcggact ttattaatgg catcttcgct 360

aaggtgaaaa acacgaaggt tttcaaagat ggagtgatgt attcagagtt ccctgcgatc 420

accattggaa gtaccttcgt gaatacttcc tatagcgtgg tggttcaacc acggacaatc 480

aactccaccc aggacggcgt caacaagctc cagggattgc tggaggtgtc agtctgtcaa 540

tataacatgt gtgagtaccc acacactatc tgtcacccta atctaggcaa ccactttaag 600

gaactgtggc actacgatac gggggtggta agttgcttat ataagagaaa tttcacctat 660

gatgttaatg caacgtacct gtactttcac ttctatcaag aaggaggaac tttctacgca 720

tatttcacag ataccggctt tgtgacgaaa ttcttattca acgtttacct cggaatggca 780

ttaagccatt attacgtgat gcctctcact tgcatcagac gccctaagga tggtttttct 840

ctggagtact gggtcactcc cctgacacca cggcagtacc tgcttgcttt taaccaggac 900

ggtatcattt ttaatgccgt cgattgtatg agcgatttta tgagcgagat aaagtgcaag 960

acccaatcta ttgctccgcc cacgggggtg tacgaactga atggttacac cgtccagccc 1020

gttgccgatg tatatagacg gaaaccagac ctgcccaatt gcaacatcga agcttggtta 1080

aacgataagt cagtgccctc ccccctcaat tgggagagga agactttctc caactgtaat 1140

ttcaacatgt caagcctgat gtctttcatt caagccgatt cgttcacttg taataatata 1200

gatgcagcaa agatctatgg tatgtgcttc agttccatca caatagataa gtttgcaata 1260

ccaaaccgtc gcaaggtgga ccttcagctc ggcaacctgg gctatctgca gtccagcaat 1320

tatagaatag acaccaccgc cacatcatgt cagctgtact ataacctccc agcagcgaac 1380

gtcagtgtta gtaggttcaa tccttctacc tggaataaaa ggtttggatt catcgaagat 1440

agtgtgttcg tacctcagcc aacaggagtg ttcaccaatc acagcgtggt ctacgcccaa 1500

cattgcttca aggcacccaa aaatttctgc ccatgtagca gttgctcctg cccgggtaag 1560

aacaatggga tcggcacctg cccagcaggc accaattcac ttacatgcga taatctgtgt 1620

acactggatc ctattacact taaggcccct gatacctaca aatgccccca gagcaagagc 1680

ctggtcggta tcggagaaca ctgttccgga cttgcagtaa aaagcgacta ttgtggaaat 1740

aactcttgca cttgtcagcc acaagccttc ctcggttggt ccgctgactc ttgtttacaa 1800

ggggataagt gtaacatctt cgcaaatttc atcttacacg atgtgaataa cggcttaaca 1860

tgcagcacag atctccagaa ggcaaacaca gagatcgaat taggagtctg cgttaattac 1920

gatctctacg ggatctctgg ccagggcatc ttcgtggagg ttaatgctac ctactacaat 1980

agttggcaaa atctgctcta cgatagcaat ggcaacctct atggattcag agactatatt 2040

actaacagga cgttcatgat tcactcgtgc tattccgggc gggtgtcagc agcttatcac 2100

gcaaattctt cagagccagc tctgctattc cgaaacataa aatgtaatta cgtgttcaat 2160

aattcactga ctcggcagct gcagccgatt aattacagct tcgacagcta ccttggttgc 2220

gttgttaacg cctacaactc cactgccata tcagttcaga cctgcgacct tactgtgggc 2280

tctggctatt gtgtcgatta ttcaaagaac ggggggagcg ggtccgcaat aacaactggc 2340

tataggttca ccaattttga gcctttcacc gtgaatagtg tcaacgatag cctggagcct 2400

gtcggaggtc tttatgagat acaaatcccc tccgagttca caattggcaa catggaagag 2460

ttcatccaga cgagttcccc aaaggtgacg atcgattgcg cggctttcgt ctgcggcgac 2520

tacgccgcat gcaagttaca actcgttgag tatggaagtt tttgcgataa tataaacgca 2580

attctgactg aagtgaacga actgctggac accactcagt tgcaggtggc aaattcgctc 2640

atgaacggcg tgacactgtc aaccaaactg aaggacggtg tcaatttcaa tgtggatgac 2700

attaacttca gccccgtact gggctgtttg ggtagtgagt gttctaaggc tagcagccgc 2760

tccgccattg aggacttgtt gtttgataaa gttaagctga gtgacgttgg atttgttgag 2820

gcgtataata actgtaccgg tggtgcagag ataagggatc tgatctgtgt ccagagttat 2880

aaggggatta aggttctccc cccgctactc tcggagaatc agatatcagg atacaccctg 2940

gccgctacct cagcctcgct gtttccccct tggaccgctg ccgccggtgt cccattttat 3000

ttgaatgtgc agtatcggat caacggtctg ggagtgacaa tggacgtgct gtctcagaac 3060

cagaaactga tcgccaatgc attcaacaat gctctgcacg ccatccagca agggtttgac 3120

gctacaaatt ctgccctcgt aaaaatccag gccgtggtga atgctaacgc cgaagccctt 3180

aataatctgc tccagcagct ttctaaccgc tttggagcta tttctgcctc actgcaggaa 3240

attctatcca gactggatcc ccctgaggca gaagcccaaa tcgaccgtct cataaacggc 3300

agactcactg ctcttaacgc ctacgttagt caacaattga gcgattcgac cttggtgaaa 3360

ttcagcgcag ctcaggctat ggagaaggtg aacgagtgcg tgaagtcaca gagctccaga 3420

atcaatttct gtggcaatgg gaaccatatc atctccttgg ttcagaatgc tccctacggc 3480

ctgtatttca tccacttcaa ctacgtgccc acgaagtacg ttacagccaa agtgtccccc 3540

ggactgtgca tcgctggtaa caggggcatt gcaccaaaat ccggctactt cgtcaatgtc 3600

aacaacacat ggatgtatac tgggagtggt tattattacc ctgaacctat aacagagaac 3660

aatgtagtag tcatgtccac atgcgccgtc aattatacta aggcccccta tgttatgctc 3720

aacacttcaa ttcccaatct cccggatttc aaagaagagc tggatcagtg gtttaagaat 3780

cagacatccg tggcccctga cttaagcttg gattatatca atgtgacttt tttagactta 3840

caggtcgaga tgaaccgact ccaggaagct ataaaagtac tgaaccactc ctatatcaat 3900

ctgaaagata tcggtacata cgaatattac gtaaaatggc cttggtatgt gtggctacta 3960

atttgccttg cgggcgtggc tatgctggtc ctgctgttct tcatttgctg ctgtactggg 4020

tgcggtactt cctgcttcaa aaagtgcggt ggttgctgcg acgactacac tgggtaccag 4080

gagcttgtca ttaagacctc gcatgacgac tga 4113

<210> 138

<211> 4065

<212> DNA

<213> artificial sequence

<220>

<223> PDI-OC43-H5iTMCT-DNA

<400> 138

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgatcgg cgatctgaat tgtaccctgg atccccgcct gaaagggagc 120

tttaacaacc gagatacagg acccccgtct atatccatag atacagtgga tgttacgaac 180

gggctcggca cctactatgt gctagaccga gtttatttga acaccacctt attcctcaat 240

ggatactacc caacttcagg tagtacttac agaaacatgg cgctgaaggg tacggatctg 300

ctgagcaccc tatggtttaa acctcccttc ctctcggact ttattaatgg catcttcgct 360

aaggtgaaaa acacgaaggt tttcaaagat ggagtgatgt attcagagtt ccctgcgatc 420

accattggaa gtaccttcgt gaatacttcc tatagcgtgg tggttcaacc acggacaatc 480

aactccaccc aggacggcgt caacaagctc cagggattgc tggaggtgtc agtctgtcaa 540

tataacatgt gtgagtaccc acacactatc tgtcacccta atctaggcaa ccactttaag 600

gaactgtggc actacgatac gggggtggta agttgcttat ataagagaaa tttcacctat 660

gatgttaatg caacgtacct gtactttcac ttctatcaag aaggaggaac tttctacgca 720

tatttcacag ataccggctt tgtgacgaaa ttcttattca acgtttacct cggaatggca 780

ttaagccatt attacgtgat gcctctcact tgcatcagac gccctaagga tggtttttct 840

ctggagtact gggtcactcc cctgacacca cggcagtacc tgcttgcttt taaccaggac 900

ggtatcattt ttaatgccgt cgattgtatg agcgatttta tgagcgagat aaagtgcaag 960

acccaatcta ttgctccgcc cacgggggtg tacgaactga atggttacac cgtccagccc 1020

gttgccgatg tatatagacg gaaaccagac ctgcccaatt gcaacatcga agcttggtta 1080

aacgataagt cagtgccctc ccccctcaat tgggagagga agactttctc caactgtaat 1140

ttcaacatgt caagcctgat gtctttcatt caagccgatt cgttcacttg taataatata 1200

gatgcagcaa agatctatgg tatgtgcttc agttccatca caatagataa gtttgcaata 1260

ccaaaccgtc gcaaggtgga ccttcagctc ggcaacctgg gctatctgca gtccagcaat 1320

tatagaatag acaccaccgc cacatcatgt cagctgtact ataacctccc agcagcgaac 1380

gtcagtgtta gtaggttcaa tccttctacc tggaataaaa ggtttggatt catcgaagat 1440

agtgtgttcg tacctcagcc aacaggagtg ttcaccaatc acagcgtggt ctacgcccaa 1500

cattgcttca aggcacccaa aaatttctgc ccatgtagca gttgctcctg cccgggtaag 1560

aacaatggga tcggcacctg cccagcaggc accaattcac ttacatgcga taatctgtgt 1620

acactggatc ctattacact taaggcccct gatacctaca aatgccccca gagcaagagc 1680

ctggtcggta tcggagaaca ctgttccgga cttgcagtaa aaagcgacta ttgtggaaat 1740

aactcttgca cttgtcagcc acaagccttc ctcggttggt ccgctgactc ttgtttacaa 1800

ggggataagt gtaacatctt cgcaaatttc atcttacacg atgtgaataa cggcttaaca 1860

tgcagcacag atctccagaa ggcaaacaca gagatcgaat taggagtctg cgttaattac 1920

gatctctacg ggatctctgg ccagggcatc ttcgtggagg ttaatgctac ctactacaat 1980

agttggcaaa atctgctcta cgatagcaat ggcaacctct atggattcag agactatatt 2040

actaacagga cgttcatgat tcactcgtgc tattccgggc gggtgtcagc agcttatcac 2100

gcaaattctt cagagccagc tctgctattc cgaaacataa aatgtaatta cgtgttcaat 2160

aattcactga ctcggcagct gcagccgatt aattacagct tcgacagcta ccttggttgc 2220

gttgttaacg cctacaactc cactgccata tcagttcaga cctgcgacct tactgtgggc 2280

tctggctatt gtgtcgatta ttcaaagaac ggggggagcg ggtccgcaat aacaactggc 2340

tataggttca ccaattttga gcctttcacc gtgaatagtg tcaacgatag cctggagcct 2400

gtcggaggtc tttatgagat acaaatcccc tccgagttca caattggcaa catggaagag 2460

ttcatccaga cgagttcccc aaaggtgacg atcgattgcg cggctttcgt ctgcggcgac 2520

tacgccgcat gcaagttaca actcgttgag tatggaagtt tttgcgataa tataaacgca 2580

attctgactg aagtgaacga actgctggac accactcagt tgcaggtggc aaattcgctc 2640

atgaacggcg tgacactgtc aaccaaactg aaggacggtg tcaatttcaa tgtggatgac 2700

attaacttca gccccgtact gggctgtttg ggtagtgagt gttctaaggc tagcagccgc 2760

tccgccattg aggacttgtt gtttgataaa gttaagctga gtgacgttgg atttgttgag 2820

gcgtataata actgtaccgg tggtgcagag ataagggatc tgatctgtgt ccagagttat 2880

aaggggatta aggttctccc cccgctactc tcggagaatc agatatcagg atacaccctg 2940

gccgctacct cagcctcgct gtttccccct tggaccgctg ccgccggtgt cccattttat 3000

ttgaatgtgc agtatcggat caacggtctg ggagtgacaa tggacgtgct gtctcagaac 3060

cagaaactga tcgccaatgc attcaacaat gctctgcacg ccatccagca agggtttgac 3120

gctacaaatt ctgccctcgt aaaaatccag gccgtggtga atgctaacgc cgaagccctt 3180

aataatctgc tccagcagct ttctaaccgc tttggagcta tttctgcctc actgcaggaa 3240

attctatcca gactggatcc ccctgaggca gaagcccaaa tcgaccgtct cataaacggc 3300

agactcactg ctcttaacgc ctacgttagt caacaattga gcgattcgac cttggtgaaa 3360

ttcagcgcag ctcaggctat ggagaaggtg aacgagtgcg tgaagtcaca gagctccaga 3420

atcaatttct gtggcaatgg gaaccatatc atctccttgg ttcagaatgc tccctacggc 3480

ctgtatttca tccacttcaa ctacgtgccc acgaagtacg ttacagccaa agtgtccccc 3540

ggactgtgca tcgctggtaa caggggcatt gcaccaaaat ccggctactt cgtcaatgtc 3600

aacaacacat ggatgtatac tgggagtggt tattattacc ctgaacctat aacagagaac 3660

aatgtagtag tcatgtccac atgcgccgtc aattatacta aggcccccta tgttatgctc 3720

aacacttcaa ttcccaatct cccggatttc aaagaagagc tggatcagtg gtttaagaat 3780

cagacatccg tggcccctga cttaagcttg gattatatca atgtgacttt tttagactta 3840

caggtcgaga tgaaccgact ccaggaagct ataaaagtac tgaaccactc ctatatcaat 3900

ctgaaagata tcggtacata cgaatattac gtaaaatggc cttggtatca aatactgtca 3960

atttattcaa cagtggcgag ttccctagca ctggcaatca tgatggctgg tctatcttta 4020

tggatgtgct ccaatggatc gttacaatgc agaatttgca tttga 4065

<210> 139

<211> 4056

<212> DNA

<213> artificial sequence

<220>

<223> PDI-OC43-H5iCT-DNA

<400> 139

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgatcgg cgatctgaat tgtaccctgg atccccgcct gaaagggagc 120

tttaacaacc gagatacagg acccccgtct atatccatag atacagtgga tgttacgaac 180

gggctcggca cctactatgt gctagaccga gtttatttga acaccacctt attcctcaat 240

ggatactacc caacttcagg tagtacttac agaaacatgg cgctgaaggg tacggatctg 300

ctgagcaccc tatggtttaa acctcccttc ctctcggact ttattaatgg catcttcgct 360

aaggtgaaaa acacgaaggt tttcaaagat ggagtgatgt attcagagtt ccctgcgatc 420

accattggaa gtaccttcgt gaatacttcc tatagcgtgg tggttcaacc acggacaatc 480

aactccaccc aggacggcgt caacaagctc cagggattgc tggaggtgtc agtctgtcaa 540

tataacatgt gtgagtaccc acacactatc tgtcacccta atctaggcaa ccactttaag 600

gaactgtggc actacgatac gggggtggta agttgcttat ataagagaaa tttcacctat 660

gatgttaatg caacgtacct gtactttcac ttctatcaag aaggaggaac tttctacgca 720

tatttcacag ataccggctt tgtgacgaaa ttcttattca acgtttacct cggaatggca 780

ttaagccatt attacgtgat gcctctcact tgcatcagac gccctaagga tggtttttct 840

ctggagtact gggtcactcc cctgacacca cggcagtacc tgcttgcttt taaccaggac 900

ggtatcattt ttaatgccgt cgattgtatg agcgatttta tgagcgagat aaagtgcaag 960

acccaatcta ttgctccgcc cacgggggtg tacgaactga atggttacac cgtccagccc 1020

gttgccgatg tatatagacg gaaaccagac ctgcccaatt gcaacatcga agcttggtta 1080

aacgataagt cagtgccctc ccccctcaat tgggagagga agactttctc caactgtaat 1140

ttcaacatgt caagcctgat gtctttcatt caagccgatt cgttcacttg taataatata 1200

gatgcagcaa agatctatgg tatgtgcttc agttccatca caatagataa gtttgcaata 1260

ccaaaccgtc gcaaggtgga ccttcagctc ggcaacctgg gctatctgca gtccagcaat 1320

tatagaatag acaccaccgc cacatcatgt cagctgtact ataacctccc agcagcgaac 1380

gtcagtgtta gtaggttcaa tccttctacc tggaataaaa ggtttggatt catcgaagat 1440

agtgtgttcg tacctcagcc aacaggagtg ttcaccaatc acagcgtggt ctacgcccaa 1500

cattgcttca aggcacccaa aaatttctgc ccatgtagca gttgctcctg cccgggtaag 1560

aacaatggga tcggcacctg cccagcaggc accaattcac ttacatgcga taatctgtgt 1620

acactggatc ctattacact taaggcccct gatacctaca aatgccccca gagcaagagc 1680

ctggtcggta tcggagaaca ctgttccgga cttgcagtaa aaagcgacta ttgtggaaat 1740

aactcttgca cttgtcagcc acaagccttc ctcggttggt ccgctgactc ttgtttacaa 1800

ggggataagt gtaacatctt cgcaaatttc atcttacacg atgtgaataa cggcttaaca 1860

tgcagcacag atctccagaa ggcaaacaca gagatcgaat taggagtctg cgttaattac 1920

gatctctacg ggatctctgg ccagggcatc ttcgtggagg ttaatgctac ctactacaat 1980

agttggcaaa atctgctcta cgatagcaat ggcaacctct atggattcag agactatatt 2040

actaacagga cgttcatgat tcactcgtgc tattccgggc gggtgtcagc agcttatcac 2100

gcaaattctt cagagccagc tctgctattc cgaaacataa aatgtaatta cgtgttcaat 2160

aattcactga ctcggcagct gcagccgatt aattacagct tcgacagcta ccttggttgc 2220

gttgttaacg cctacaactc cactgccata tcagttcaga cctgcgacct tactgtgggc 2280

tctggctatt gtgtcgatta ttcaaagaac ggggggagcg ggtccgcaat aacaactggc 2340

tataggttca ccaattttga gcctttcacc gtgaatagtg tcaacgatag cctggagcct 2400

gtcggaggtc tttatgagat acaaatcccc tccgagttca caattggcaa catggaagag 2460

ttcatccaga cgagttcccc aaaggtgacg atcgattgcg cggctttcgt ctgcggcgac 2520

tacgccgcat gcaagttaca actcgttgag tatggaagtt tttgcgataa tataaacgca 2580

attctgactg aagtgaacga actgctggac accactcagt tgcaggtggc aaattcgctc 2640

atgaacggcg tgacactgtc aaccaaactg aaggacggtg tcaatttcaa tgtggatgac 2700

attaacttca gccccgtact gggctgtttg ggtagtgagt gttctaaggc tagcagccgc 2760

tccgccattg aggacttgtt gtttgataaa gttaagctga gtgacgttgg atttgttgag 2820

gcgtataata actgtaccgg tggtgcagag ataagggatc tgatctgtgt ccagagttat 2880

aaggggatta aggttctccc cccgctactc tcggagaatc agatatcagg atacaccctg 2940

gccgctacct cagcctcgct gtttccccct tggaccgctg ccgccggtgt cccattttat 3000

ttgaatgtgc agtatcggat caacggtctg ggagtgacaa tggacgtgct gtctcagaac 3060

cagaaactga tcgccaatgc attcaacaat gctctgcacg ccatccagca agggtttgac 3120

gctacaaatt ctgccctcgt aaaaatccag gccgtggtga atgctaacgc cgaagccctt 3180

aataatctgc tccagcagct ttctaaccgc tttggagcta tttctgcctc actgcaggaa 3240

attctatcca gactggatcc ccctgaggca gaagcccaaa tcgaccgtct cataaacggc 3300

agactcactg ctcttaacgc ctacgttagt caacaattga gcgattcgac cttggtgaaa 3360

ttcagcgcag ctcaggctat ggagaaggtg aacgagtgcg tgaagtcaca gagctccaga 3420

atcaatttct gtggcaatgg gaaccatatc atctccttgg ttcagaatgc tccctacggc 3480

ctgtatttca tccacttcaa ctacgtgccc acgaagtacg ttacagccaa agtgtccccc 3540

ggactgtgca tcgctggtaa caggggcatt gcaccaaaat ccggctactt cgtcaatgtc 3600

aacaacacat ggatgtatac tgggagtggt tattattacc ctgaacctat aacagagaac 3660

aatgtagtag tcatgtccac atgcgccgtc aattatacta aggcccccta tgttatgctc 3720

aacacttcaa ttcccaatct cccggatttc aaagaagagc tggatcagtg gtttaagaat 3780

cagacatccg tggcccctga cttaagcttg gattatatca atgtgacttt tttagactta 3840

caggtcgaga tgaaccgact ccaggaagct ataaaagtac tgaaccactc ctatatcaat 3900

ctgaaagata tcggtacata cgaatattac gtaaaatggc cttggtatgt gtggctacta 3960

atttgccttg cgggcgtggc tatgctggtc ctgctgttct tcatttcttt atggatgtgc 4020

tccaatggat cgttacaatg cagaatttgc atttga 4056

<210> 140

<211> 4047

<212> DNA

<213> artificial sequence

<220>

<223> PDI-OC43-H5iCT(V4)-DNA

<400> 140

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgatcgg cgatctgaat tgtaccctgg atccccgcct gaaagggagc 120

tttaacaacc gagatacagg acccccgtct atatccatag atacagtgga tgttacgaac 180

gggctcggca cctactatgt gctagaccga gtttatttga acaccacctt attcctcaat 240

ggatactacc caacttcagg tagtacttac agaaacatgg cgctgaaggg tacggatctg 300

ctgagcaccc tatggtttaa acctcccttc ctctcggact ttattaatgg catcttcgct 360

aaggtgaaaa acacgaaggt tttcaaagat ggagtgatgt attcagagtt ccctgcgatc 420

accattggaa gtaccttcgt gaatacttcc tatagcgtgg tggttcaacc acggacaatc 480

aactccaccc aggacggcgt caacaagctc cagggattgc tggaggtgtc agtctgtcaa 540

tataacatgt gtgagtaccc acacactatc tgtcacccta atctaggcaa ccactttaag 600

gaactgtggc actacgatac gggggtggta agttgcttat ataagagaaa tttcacctat 660

gatgttaatg caacgtacct gtactttcac ttctatcaag aaggaggaac tttctacgca 720

tatttcacag ataccggctt tgtgacgaaa ttcttattca acgtttacct cggaatggca 780

ttaagccatt attacgtgat gcctctcact tgcatcagac gccctaagga tggtttttct 840

ctggagtact gggtcactcc cctgacacca cggcagtacc tgcttgcttt taaccaggac 900

ggtatcattt ttaatgccgt cgattgtatg agcgatttta tgagcgagat aaagtgcaag 960

acccaatcta ttgctccgcc cacgggggtg tacgaactga atggttacac cgtccagccc 1020

gttgccgatg tatatagacg gaaaccagac ctgcccaatt gcaacatcga agcttggtta 1080

aacgataagt cagtgccctc ccccctcaat tgggagagga agactttctc caactgtaat 1140

ttcaacatgt caagcctgat gtctttcatt caagccgatt cgttcacttg taataatata 1200

gatgcagcaa agatctatgg tatgtgcttc agttccatca caatagataa gtttgcaata 1260

ccaaaccgtc gcaaggtgga ccttcagctc ggcaacctgg gctatctgca gtccagcaat 1320

tatagaatag acaccaccgc cacatcatgt cagctgtact ataacctccc agcagcgaac 1380

gtcagtgtta gtaggttcaa tccttctacc tggaataaaa ggtttggatt catcgaagat 1440

agtgtgttcg tacctcagcc aacaggagtg ttcaccaatc acagcgtggt ctacgcccaa 1500

cattgcttca aggcacccaa aaatttctgc ccatgtagca gttgctcctg cccgggtaag 1560

aacaatggga tcggcacctg cccagcaggc accaattcac ttacatgcga taatctgtgt 1620

acactggatc ctattacact taaggcccct gatacctaca aatgccccca gagcaagagc 1680

ctggtcggta tcggagaaca ctgttccgga cttgcagtaa aaagcgacta ttgtggaaat 1740

aactcttgca cttgtcagcc acaagccttc ctcggttggt ccgctgactc ttgtttacaa 1800

ggggataagt gtaacatctt cgcaaatttc atcttacacg atgtgaataa cggcttaaca 1860

tgcagcacag atctccagaa ggcaaacaca gagatcgaat taggagtctg cgttaattac 1920

gatctctacg ggatctctgg ccagggcatc ttcgtggagg ttaatgctac ctactacaat 1980

agttggcaaa atctgctcta cgatagcaat ggcaacctct atggattcag agactatatt 2040

actaacagga cgttcatgat tcactcgtgc tattccgggc gggtgtcagc agcttatcac 2100

gcaaattctt cagagccagc tctgctattc cgaaacataa aatgtaatta cgtgttcaat 2160

aattcactga ctcggcagct gcagccgatt aattacagct tcgacagcta ccttggttgc 2220

gttgttaacg cctacaactc cactgccata tcagttcaga cctgcgacct tactgtgggc 2280

tctggctatt gtgtcgatta ttcaaagaac ggggggagcg ggtccgcaat aacaactggc 2340

tataggttca ccaattttga gcctttcacc gtgaatagtg tcaacgatag cctggagcct 2400

gtcggaggtc tttatgagat acaaatcccc tccgagttca caattggcaa catggaagag 2460

ttcatccaga cgagttcccc aaaggtgacg atcgattgcg cggctttcgt ctgcggcgac 2520

tacgccgcat gcaagttaca actcgttgag tatggaagtt tttgcgataa tataaacgca 2580

attctgactg aagtgaacga actgctggac accactcagt tgcaggtggc aaattcgctc 2640

atgaacggcg tgacactgtc aaccaaactg aaggacggtg tcaatttcaa tgtggatgac 2700

attaacttca gccccgtact gggctgtttg ggtagtgagt gttctaaggc tagcagccgc 2760

tccgccattg aggacttgtt gtttgataaa gttaagctga gtgacgttgg atttgttgag 2820

gcgtataata actgtaccgg tggtgcagag ataagggatc tgatctgtgt ccagagttat 2880

aaggggatta aggttctccc cccgctactc tcggagaatc agatatcagg atacaccctg 2940

gccgctacct cagcctcgct gtttccccct tggaccgctg ccgccggtgt cccattttat 3000

ttgaatgtgc agtatcggat caacggtctg ggagtgacaa tggacgtgct gtctcagaac 3060

cagaaactga tcgccaatgc attcaacaat gctctgcacg ccatccagca agggtttgac 3120

gctacaaatt ctgccctcgt aaaaatccag gccgtggtga atgctaacgc cgaagccctt 3180

aataatctgc tccagcagct ttctaaccgc tttggagcta tttctgcctc actgcaggaa 3240

attctatcca gactggatcc ccctgaggca gaagcccaaa tcgaccgtct cataaacggc 3300

agactcactg ctcttaacgc ctacgttagt caacaattga gcgattcgac cttggtgaaa 3360

ttcagcgcag ctcaggctat ggagaaggtg aacgagtgcg tgaagtcaca gagctccaga 3420

atcaatttct gtggcaatgg gaaccatatc atctccttgg ttcagaatgc tccctacggc 3480

ctgtatttca tccacttcaa ctacgtgccc acgaagtacg ttacagccaa agtgtccccc 3540

ggactgtgca tcgctggtaa caggggcatt gcaccaaaat ccggctactt cgtcaatgtc 3600

aacaacacat ggatgtatac tgggagtggt tattattacc ctgaacctat aacagagaac 3660

aatgtagtag tcatgtccac atgcgccgtc aattatacta aggcccccta tgttatgctc 3720

aacacttcaa ttcccaatct cccggatttc aaagaagagc tggatcagtg gtttaagaat 3780

cagacatccg tggcccctga cttaagcttg gattatatca atgtgacttt tttagactta 3840

caggtcgaga tgaaccgact ccaggaagct ataaaagtac tgaaccactc ctatatcaat 3900

ctgaaagata tcggtacata cgaatattac gtaaaatggc cttggtatgt gtggctacta 3960

atttgccttg cgggcgtggc tatgctggtc ctgctgttct tcatttgctg ctccaatgga 4020

tcgttacaat gcagaatttg catttga 4047

<210> 141

<211> 4056

<212> DNA

<213> artificial sequence

<220>

<223> PDI-OC43-H1cCT-DNA

<400> 141

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cggtgatcgg cgatctgaat tgtaccctgg atccccgcct gaaagggagc 120

tttaacaacc gagatacagg acccccgtct atatccatag atacagtgga tgttacgaac 180

gggctcggca cctactatgt gctagaccga gtttatttga acaccacctt attcctcaat 240

ggatactacc caacttcagg tagtacttac agaaacatgg cgctgaaggg tacggatctg 300

ctgagcaccc tatggtttaa acctcccttc ctctcggact ttattaatgg catcttcgct 360

aaggtgaaaa acacgaaggt tttcaaagat ggagtgatgt attcagagtt ccctgcgatc 420

accattggaa gtaccttcgt gaatacttcc tatagcgtgg tggttcaacc acggacaatc 480

aactccaccc aggacggcgt caacaagctc cagggattgc tggaggtgtc agtctgtcaa 540

tataacatgt gtgagtaccc acacactatc tgtcacccta atctaggcaa ccactttaag 600

gaactgtggc actacgatac gggggtggta agttgcttat ataagagaaa tttcacctat 660

gatgttaatg caacgtacct gtactttcac ttctatcaag aaggaggaac tttctacgca 720

tatttcacag ataccggctt tgtgacgaaa ttcttattca acgtttacct cggaatggca 780

ttaagccatt attacgtgat gcctctcact tgcatcagac gccctaagga tggtttttct 840

ctggagtact gggtcactcc cctgacacca cggcagtacc tgcttgcttt taaccaggac 900

ggtatcattt ttaatgccgt cgattgtatg agcgatttta tgagcgagat aaagtgcaag 960

acccaatcta ttgctccgcc cacgggggtg tacgaactga atggttacac cgtccagccc 1020

gttgccgatg tatatagacg gaaaccagac ctgcccaatt gcaacatcga agcttggtta 1080

aacgataagt cagtgccctc ccccctcaat tgggagagga agactttctc caactgtaat 1140

ttcaacatgt caagcctgat gtctttcatt caagccgatt cgttcacttg taataatata 1200

gatgcagcaa agatctatgg tatgtgcttc agttccatca caatagataa gtttgcaata 1260

ccaaaccgtc gcaaggtgga ccttcagctc ggcaacctgg gctatctgca gtccagcaat 1320

tatagaatag acaccaccgc cacatcatgt cagctgtact ataacctccc agcagcgaac 1380

gtcagtgtta gtaggttcaa tccttctacc tggaataaaa ggtttggatt catcgaagat 1440

agtgtgttcg tacctcagcc aacaggagtg ttcaccaatc acagcgtggt ctacgcccaa 1500

cattgcttca aggcacccaa aaatttctgc ccatgtagca gttgctcctg cccgggtaag 1560

aacaatggga tcggcacctg cccagcaggc accaattcac ttacatgcga taatctgtgt 1620

acactggatc ctattacact taaggcccct gatacctaca aatgccccca gagcaagagc 1680

ctggtcggta tcggagaaca ctgttccgga cttgcagtaa aaagcgacta ttgtggaaat 1740

aactcttgca cttgtcagcc acaagccttc ctcggttggt ccgctgactc ttgtttacaa 1800

ggggataagt gtaacatctt cgcaaatttc atcttacacg atgtgaataa cggcttaaca 1860

tgcagcacag atctccagaa ggcaaacaca gagatcgaat taggagtctg cgttaattac 1920

gatctctacg ggatctctgg ccagggcatc ttcgtggagg ttaatgctac ctactacaat 1980

agttggcaaa atctgctcta cgatagcaat ggcaacctct atggattcag agactatatt 2040

actaacagga cgttcatgat tcactcgtgc tattccgggc gggtgtcagc agcttatcac 2100

gcaaattctt cagagccagc tctgctattc cgaaacataa aatgtaatta cgtgttcaat 2160

aattcactga ctcggcagct gcagccgatt aattacagct tcgacagcta ccttggttgc 2220

gttgttaacg cctacaactc cactgccata tcagttcaga cctgcgacct tactgtgggc 2280

tctggctatt gtgtcgatta ttcaaagaac ggggggagcg ggtccgcaat aacaactggc 2340

tataggttca ccaattttga gcctttcacc gtgaatagtg tcaacgatag cctggagcct 2400

gtcggaggtc tttatgagat acaaatcccc tccgagttca caattggcaa catggaagag 2460

ttcatccaga cgagttcccc aaaggtgacg atcgattgcg cggctttcgt ctgcggcgac 2520

tacgccgcat gcaagttaca actcgttgag tatggaagtt tttgcgataa tataaacgca 2580

attctgactg aagtgaacga actgctggac accactcagt tgcaggtggc aaattcgctc 2640

atgaacggcg tgacactgtc aaccaaactg aaggacggtg tcaatttcaa tgtggatgac 2700

attaacttca gccccgtact gggctgtttg ggtagtgagt gttctaaggc tagcagccgc 2760

tccgccattg aggacttgtt gtttgataaa gttaagctga gtgacgttgg atttgttgag 2820

gcgtataata actgtaccgg tggtgcagag ataagggatc tgatctgtgt ccagagttat 2880

aaggggatta aggttctccc cccgctactc tcggagaatc agatatcagg atacaccctg 2940

gccgctacct cagcctcgct gtttccccct tggaccgctg ccgccggtgt cccattttat 3000

ttgaatgtgc agtatcggat caacggtctg ggagtgacaa tggacgtgct gtctcagaac 3060

cagaaactga tcgccaatgc attcaacaat gctctgcacg ccatccagca agggtttgac 3120

gctacaaatt ctgccctcgt aaaaatccag gccgtggtga atgctaacgc cgaagccctt 3180

aataatctgc tccagcagct ttctaaccgc tttggagcta tttctgcctc actgcaggaa 3240

attctatcca gactggatcc ccctgaggca gaagcccaaa tcgaccgtct cataaacggc 3300

agactcactg ctcttaacgc ctacgttagt caacaattga gcgattcgac cttggtgaaa 3360

ttcagcgcag ctcaggctat ggagaaggtg aacgagtgcg tgaagtcaca gagctccaga 3420

atcaatttct gtggcaatgg gaaccatatc atctccttgg ttcagaatgc tccctacggc 3480

ctgtatttca tccacttcaa ctacgtgccc acgaagtacg ttacagccaa agtgtccccc 3540

ggactgtgca tcgctggtaa caggggcatt gcaccaaaat ccggctactt cgtcaatgtc 3600

aacaacacat ggatgtatac tgggagtggt tattattacc ctgaacctat aacagagaac 3660

aatgtagtag tcatgtccac atgcgccgtc aattatacta aggcccccta tgttatgctc 3720

aacacttcaa ttcccaatct cccggatttc aaagaagagc tggatcagtg gtttaagaat 3780

cagacatccg tggcccctga cttaagcttg gattatatca atgtgacttt tttagactta 3840

caggtcgaga tgaaccgact ccaggaagct ataaaagtac tgaaccactc ctatatcaat 3900

ctgaaagata tcggtacata cgaatattac gtaaaatggc cttggtatgt gtggctacta 3960

atttgccttg cgggcgtggc tatgctggtc ctgctgttct tcattagctt ctggatgtgc 4020

tctaatgggt ctctacagtg tagaatatgt atttga 4056

<210> 142

<211> 1370

<212> PRT

<213> artificial sequence

<220>

<223> PDI-OC43-wtTMCT-AA

<400> 142

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Ile Gly Asp Leu Asn Cys Thr

20 25 30

Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn Asn Arg Asp Thr Gly Pro

35 40 45

Pro Ser Ile Ser Ile Asp Thr Val Asp Val Thr Asn Gly Leu Gly Thr

50 55 60

Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn Thr Thr Leu Phe Leu Asn

65 70 75 80

Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr Arg Asn Met Ala Leu Lys

85 90 95

Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe Lys Pro Pro Phe Leu Ser

100 105 110

Asp Phe Ile Asn Gly Ile Phe Ala Lys Val Lys Asn Thr Lys Val Phe

115 120 125

Lys Asp Gly Val Met Tyr Ser Glu Phe Pro Ala Ile Thr Ile Gly Ser

130 135 140

Thr Phe Val Asn Thr Ser Tyr Ser Val Val Val Gln Pro Arg Thr Ile

145 150 155 160

Asn Ser Thr Gln Asp Gly Val Asn Lys Leu Gln Gly Leu Leu Glu Val

165 170 175

Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr Pro His Thr Ile Cys His

180 185 190

Pro Asn Leu Gly Asn His Phe Lys Glu Leu Trp His Tyr Asp Thr Gly

195 200 205

Val Val Ser Cys Leu Tyr Lys Arg Asn Phe Thr Tyr Asp Val Asn Ala

210 215 220

Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu Gly Gly Thr Phe Tyr Ala

225 230 235 240

Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys Phe Leu Phe Asn Val Tyr

245 250 255

Leu Gly Met Ala Leu Ser His Tyr Tyr Val Met Pro Leu Thr Cys Ile

260 265 270

Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu Tyr Trp Val Thr Pro Leu

275 280 285

Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn Gln Asp Gly Ile Ile Phe

290 295 300

Asn Ala Val Asp Cys Met Ser Asp Phe Met Ser Glu Ile Lys Cys Lys

305 310 315 320

Thr Gln Ser Ile Ala Pro Pro Thr Gly Val Tyr Glu Leu Asn Gly Tyr

325 330 335

Thr Val Gln Pro Val Ala Asp Val Tyr Arg Arg Lys Pro Asp Leu Pro

340 345 350

Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp Lys Ser Val Pro Ser Pro

355 360 365

Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn Cys Asn Phe Asn Met Ser

370 375 380

Ser Leu Met Ser Phe Ile Gln Ala Asp Ser Phe Thr Cys Asn Asn Ile

385 390 395 400

Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe Ser Ser Ile Thr Ile Asp

405 410 415

Lys Phe Ala Ile Pro Asn Arg Arg Lys Val Asp Leu Gln Leu Gly Asn

420 425 430

Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg Ile Asp Thr Thr Ala Thr

435 440 445

Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala Ala Asn Val Ser Val Ser

450 455 460

Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg Phe Gly Phe Ile Glu Asp

465 470 475 480

Ser Val Phe Val Pro Gln Pro Thr Gly Val Phe Thr Asn His Ser Val

485 490 495

Val Tyr Ala Gln His Cys Phe Lys Ala Pro Lys Asn Phe Cys Pro Cys

500 505 510

Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn Gly Ile Gly Thr Cys Pro

515 520 525

Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn Leu Cys Thr Leu Asp Pro

530 535 540

Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys Cys Pro Gln Ser Lys Ser

545 550 555 560

Leu Val Gly Ile Gly Glu His Cys Ser Gly Leu Ala Val Lys Ser Asp

565 570 575

Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln Pro Gln Ala Phe Leu Gly

580 585 590

Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp Lys Cys Asn Ile Phe Ala

595 600 605

Asn Phe Ile Leu His Asp Val Asn Asn Gly Leu Thr Cys Ser Thr Asp

610 615 620

Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu Gly Val Cys Val Asn Tyr

625 630 635 640

Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile Phe Val Glu Val Asn Ala

645 650 655

Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn

660 665 670

Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn Arg Thr Phe Met Ile His

675 680 685

Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala Tyr His Ala Asn Ser Ser

690 695 700

Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys Cys Asn Tyr Val Phe Asn

705 710 715 720

Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile Asn Tyr Ser Phe Asp Ser

725 730 735

Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn Ser Thr Ala Ile Ser Val

740 745 750

Gln Thr Cys Asp Leu Thr Val Gly Ser Gly Tyr Cys Val Asp Tyr Ser

755 760 765

Lys Asn Gly Gly Ser Gly Ser Ala Ile Thr Thr Gly Tyr Arg Phe Thr

770 775 780

Asn Phe Glu Pro Phe Thr Val Asn Ser Val Asn Asp Ser Leu Glu Pro

785 790 795 800

Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro Ser Glu Phe Thr Ile Gly

805 810 815

Asn Met Glu Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp

820 825 830

Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala Ala Cys Lys Leu Gln Leu

835 840 845

Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile Asn Ala Ile Leu Thr Glu

850 855 860

Val Asn Glu Leu Leu Asp Thr Thr Gln Leu Gln Val Ala Asn Ser Leu

865 870 875 880

Met Asn Gly Val Thr Leu Ser Thr Lys Leu Lys Asp Gly Val Asn Phe

885 890 895

Asn Val Asp Asp Ile Asn Phe Ser Pro Val Leu Gly Cys Leu Gly Ser

900 905 910

Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala Ile Glu Asp Leu Leu Phe

915 920 925

Asp Lys Val Lys Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn

930 935 940

Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu Ile Cys Val Gln Ser Tyr

945 950 955 960

Lys Gly Ile Lys Val Leu Pro Pro Leu Leu Ser Glu Asn Gln Ile Ser

965 970 975

Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser Leu Phe Pro Pro Trp Thr

980 985 990

Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn Val Gln Tyr Arg Ile Asn

995 1000 1005

Gly Leu Gly Val Thr Met Asp Val Leu Ser Gln Asn Gln Lys Leu Ile

1010 1015 1020

Ala Asn Ala Phe Asn Asn Ala Leu His Ala Ile Gln Gln Gly Phe Asp

1025 1030 1035 1040

Ala Thr Asn Ser Ala Leu Val Lys Ile Gln Ala Val Val Asn Ala Asn

1045 1050 1055

Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln Leu Ser Asn Arg Phe Gly

1060 1065 1070

Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Pro Pro

1075 1080 1085

Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala

1090 1095 1100

Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys

1105 1110 1115 1120

Phe Ser Ala Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser

1125 1130 1135

Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser

1140 1145 1150

Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr

1155 1160 1165

Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys Ile

1170 1175 1180

Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val Asn Val

1185 1190 1195 1200

Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr Pro Glu Pro

1205 1210 1215

Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys Ala Val Asn Tyr

1220 1225 1230

Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser Ile Pro Asn Leu Pro

1235 1240 1245

Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe Lys Asn Gln Thr Ser Val

1250 1255 1260

Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn Val Thr Phe Leu Asp Leu

1265 1270 1275 1280

Gln Val Glu Met Asn Arg Leu Gln Glu Ala Ile Lys Val Leu Asn His

1285 1290 1295

Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr Tyr Glu Tyr Tyr Val Lys

1300 1305 1310

Trp Pro Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met

1315 1320 1325

Leu Val Leu Leu Phe Phe Ile Cys Cys Cys Thr Gly Cys Gly Thr Ser

1330 1335 1340

Cys Phe Lys Lys Cys Gly Gly Cys Cys Asp Asp Tyr Thr Gly Tyr Gln

1345 1350 1355 1360

Glu Leu Val Ile Lys Thr Ser His Asp Asp

1365 1370

<210> 143

<211> 1354

<212> PRT

<213> artificial sequence

<220>

<223> PDI-OC43-H5iTMCT-AA

<400> 143

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Ile Gly Asp Leu Asn Cys Thr

20 25 30

Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn Asn Arg Asp Thr Gly Pro

35 40 45

Pro Ser Ile Ser Ile Asp Thr Val Asp Val Thr Asn Gly Leu Gly Thr

50 55 60

Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn Thr Thr Leu Phe Leu Asn

65 70 75 80

Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr Arg Asn Met Ala Leu Lys

85 90 95

Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe Lys Pro Pro Phe Leu Ser

100 105 110

Asp Phe Ile Asn Gly Ile Phe Ala Lys Val Lys Asn Thr Lys Val Phe

115 120 125

Lys Asp Gly Val Met Tyr Ser Glu Phe Pro Ala Ile Thr Ile Gly Ser

130 135 140

Thr Phe Val Asn Thr Ser Tyr Ser Val Val Val Gln Pro Arg Thr Ile

145 150 155 160

Asn Ser Thr Gln Asp Gly Val Asn Lys Leu Gln Gly Leu Leu Glu Val

165 170 175

Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr Pro His Thr Ile Cys His

180 185 190

Pro Asn Leu Gly Asn His Phe Lys Glu Leu Trp His Tyr Asp Thr Gly

195 200 205

Val Val Ser Cys Leu Tyr Lys Arg Asn Phe Thr Tyr Asp Val Asn Ala

210 215 220

Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu Gly Gly Thr Phe Tyr Ala

225 230 235 240

Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys Phe Leu Phe Asn Val Tyr

245 250 255

Leu Gly Met Ala Leu Ser His Tyr Tyr Val Met Pro Leu Thr Cys Ile

260 265 270

Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu Tyr Trp Val Thr Pro Leu

275 280 285

Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn Gln Asp Gly Ile Ile Phe

290 295 300

Asn Ala Val Asp Cys Met Ser Asp Phe Met Ser Glu Ile Lys Cys Lys

305 310 315 320

Thr Gln Ser Ile Ala Pro Pro Thr Gly Val Tyr Glu Leu Asn Gly Tyr

325 330 335

Thr Val Gln Pro Val Ala Asp Val Tyr Arg Arg Lys Pro Asp Leu Pro

340 345 350

Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp Lys Ser Val Pro Ser Pro

355 360 365

Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn Cys Asn Phe Asn Met Ser

370 375 380

Ser Leu Met Ser Phe Ile Gln Ala Asp Ser Phe Thr Cys Asn Asn Ile

385 390 395 400

Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe Ser Ser Ile Thr Ile Asp

405 410 415

Lys Phe Ala Ile Pro Asn Arg Arg Lys Val Asp Leu Gln Leu Gly Asn

420 425 430

Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg Ile Asp Thr Thr Ala Thr

435 440 445

Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala Ala Asn Val Ser Val Ser

450 455 460

Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg Phe Gly Phe Ile Glu Asp

465 470 475 480

Ser Val Phe Val Pro Gln Pro Thr Gly Val Phe Thr Asn His Ser Val

485 490 495

Val Tyr Ala Gln His Cys Phe Lys Ala Pro Lys Asn Phe Cys Pro Cys

500 505 510

Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn Gly Ile Gly Thr Cys Pro

515 520 525

Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn Leu Cys Thr Leu Asp Pro

530 535 540

Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys Cys Pro Gln Ser Lys Ser

545 550 555 560

Leu Val Gly Ile Gly Glu His Cys Ser Gly Leu Ala Val Lys Ser Asp

565 570 575

Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln Pro Gln Ala Phe Leu Gly

580 585 590

Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp Lys Cys Asn Ile Phe Ala

595 600 605

Asn Phe Ile Leu His Asp Val Asn Asn Gly Leu Thr Cys Ser Thr Asp

610 615 620

Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu Gly Val Cys Val Asn Tyr

625 630 635 640

Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile Phe Val Glu Val Asn Ala

645 650 655

Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn

660 665 670

Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn Arg Thr Phe Met Ile His

675 680 685

Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala Tyr His Ala Asn Ser Ser

690 695 700

Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys Cys Asn Tyr Val Phe Asn

705 710 715 720

Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile Asn Tyr Ser Phe Asp Ser

725 730 735

Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn Ser Thr Ala Ile Ser Val

740 745 750

Gln Thr Cys Asp Leu Thr Val Gly Ser Gly Tyr Cys Val Asp Tyr Ser

755 760 765

Lys Asn Gly Gly Ser Gly Ser Ala Ile Thr Thr Gly Tyr Arg Phe Thr

770 775 780

Asn Phe Glu Pro Phe Thr Val Asn Ser Val Asn Asp Ser Leu Glu Pro

785 790 795 800

Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro Ser Glu Phe Thr Ile Gly

805 810 815

Asn Met Glu Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp

820 825 830

Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala Ala Cys Lys Leu Gln Leu

835 840 845

Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile Asn Ala Ile Leu Thr Glu

850 855 860

Val Asn Glu Leu Leu Asp Thr Thr Gln Leu Gln Val Ala Asn Ser Leu

865 870 875 880

Met Asn Gly Val Thr Leu Ser Thr Lys Leu Lys Asp Gly Val Asn Phe

885 890 895

Asn Val Asp Asp Ile Asn Phe Ser Pro Val Leu Gly Cys Leu Gly Ser

900 905 910

Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala Ile Glu Asp Leu Leu Phe

915 920 925

Asp Lys Val Lys Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn

930 935 940

Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu Ile Cys Val Gln Ser Tyr

945 950 955 960

Lys Gly Ile Lys Val Leu Pro Pro Leu Leu Ser Glu Asn Gln Ile Ser

965 970 975

Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser Leu Phe Pro Pro Trp Thr

980 985 990

Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn Val Gln Tyr Arg Ile Asn

995 1000 1005

Gly Leu Gly Val Thr Met Asp Val Leu Ser Gln Asn Gln Lys Leu Ile

1010 1015 1020

Ala Asn Ala Phe Asn Asn Ala Leu His Ala Ile Gln Gln Gly Phe Asp

1025 1030 1035 1040

Ala Thr Asn Ser Ala Leu Val Lys Ile Gln Ala Val Val Asn Ala Asn

1045 1050 1055

Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln Leu Ser Asn Arg Phe Gly

1060 1065 1070

Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Pro Pro

1075 1080 1085

Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala

1090 1095 1100

Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys

1105 1110 1115 1120

Phe Ser Ala Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser

1125 1130 1135

Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser

1140 1145 1150

Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr

1155 1160 1165

Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys Ile

1170 1175 1180

Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val Asn Val

1185 1190 1195 1200

Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr Pro Glu Pro

1205 1210 1215

Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys Ala Val Asn Tyr

1220 1225 1230

Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser Ile Pro Asn Leu Pro

1235 1240 1245

Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe Lys Asn Gln Thr Ser Val

1250 1255 1260

Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn Val Thr Phe Leu Asp Leu

1265 1270 1275 1280

Gln Val Glu Met Asn Arg Leu Gln Glu Ala Ile Lys Val Leu Asn His

1285 1290 1295

Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr Tyr Glu Tyr Tyr Val Lys

1300 1305 1310

Trp Pro Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser

1315 1320 1325

Leu Ala Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser

1330 1335 1340

Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1345 1350

<210> 144

<211> 1351

<212> PRT

<213> artificial sequence

<220>

<223> PDI-OC43-H5iCT-AA

<400> 144

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Ile Gly Asp Leu Asn Cys Thr

20 25 30

Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn Asn Arg Asp Thr Gly Pro

35 40 45

Pro Ser Ile Ser Ile Asp Thr Val Asp Val Thr Asn Gly Leu Gly Thr

50 55 60

Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn Thr Thr Leu Phe Leu Asn

65 70 75 80

Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr Arg Asn Met Ala Leu Lys

85 90 95

Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe Lys Pro Pro Phe Leu Ser

100 105 110

Asp Phe Ile Asn Gly Ile Phe Ala Lys Val Lys Asn Thr Lys Val Phe

115 120 125

Lys Asp Gly Val Met Tyr Ser Glu Phe Pro Ala Ile Thr Ile Gly Ser

130 135 140

Thr Phe Val Asn Thr Ser Tyr Ser Val Val Val Gln Pro Arg Thr Ile

145 150 155 160

Asn Ser Thr Gln Asp Gly Val Asn Lys Leu Gln Gly Leu Leu Glu Val

165 170 175

Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr Pro His Thr Ile Cys His

180 185 190

Pro Asn Leu Gly Asn His Phe Lys Glu Leu Trp His Tyr Asp Thr Gly

195 200 205

Val Val Ser Cys Leu Tyr Lys Arg Asn Phe Thr Tyr Asp Val Asn Ala

210 215 220

Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu Gly Gly Thr Phe Tyr Ala

225 230 235 240

Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys Phe Leu Phe Asn Val Tyr

245 250 255

Leu Gly Met Ala Leu Ser His Tyr Tyr Val Met Pro Leu Thr Cys Ile

260 265 270

Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu Tyr Trp Val Thr Pro Leu

275 280 285

Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn Gln Asp Gly Ile Ile Phe

290 295 300

Asn Ala Val Asp Cys Met Ser Asp Phe Met Ser Glu Ile Lys Cys Lys

305 310 315 320

Thr Gln Ser Ile Ala Pro Pro Thr Gly Val Tyr Glu Leu Asn Gly Tyr

325 330 335

Thr Val Gln Pro Val Ala Asp Val Tyr Arg Arg Lys Pro Asp Leu Pro

340 345 350

Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp Lys Ser Val Pro Ser Pro

355 360 365

Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn Cys Asn Phe Asn Met Ser

370 375 380

Ser Leu Met Ser Phe Ile Gln Ala Asp Ser Phe Thr Cys Asn Asn Ile

385 390 395 400

Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe Ser Ser Ile Thr Ile Asp

405 410 415

Lys Phe Ala Ile Pro Asn Arg Arg Lys Val Asp Leu Gln Leu Gly Asn

420 425 430

Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg Ile Asp Thr Thr Ala Thr

435 440 445

Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala Ala Asn Val Ser Val Ser

450 455 460

Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg Phe Gly Phe Ile Glu Asp

465 470 475 480

Ser Val Phe Val Pro Gln Pro Thr Gly Val Phe Thr Asn His Ser Val

485 490 495

Val Tyr Ala Gln His Cys Phe Lys Ala Pro Lys Asn Phe Cys Pro Cys

500 505 510

Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn Gly Ile Gly Thr Cys Pro

515 520 525

Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn Leu Cys Thr Leu Asp Pro

530 535 540

Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys Cys Pro Gln Ser Lys Ser

545 550 555 560

Leu Val Gly Ile Gly Glu His Cys Ser Gly Leu Ala Val Lys Ser Asp

565 570 575

Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln Pro Gln Ala Phe Leu Gly

580 585 590

Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp Lys Cys Asn Ile Phe Ala

595 600 605

Asn Phe Ile Leu His Asp Val Asn Asn Gly Leu Thr Cys Ser Thr Asp

610 615 620

Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu Gly Val Cys Val Asn Tyr

625 630 635 640

Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile Phe Val Glu Val Asn Ala

645 650 655

Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn

660 665 670

Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn Arg Thr Phe Met Ile His

675 680 685

Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala Tyr His Ala Asn Ser Ser

690 695 700

Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys Cys Asn Tyr Val Phe Asn

705 710 715 720

Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile Asn Tyr Ser Phe Asp Ser

725 730 735

Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn Ser Thr Ala Ile Ser Val

740 745 750

Gln Thr Cys Asp Leu Thr Val Gly Ser Gly Tyr Cys Val Asp Tyr Ser

755 760 765

Lys Asn Gly Gly Ser Gly Ser Ala Ile Thr Thr Gly Tyr Arg Phe Thr

770 775 780

Asn Phe Glu Pro Phe Thr Val Asn Ser Val Asn Asp Ser Leu Glu Pro

785 790 795 800

Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro Ser Glu Phe Thr Ile Gly

805 810 815

Asn Met Glu Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp

820 825 830

Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala Ala Cys Lys Leu Gln Leu

835 840 845

Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile Asn Ala Ile Leu Thr Glu

850 855 860

Val Asn Glu Leu Leu Asp Thr Thr Gln Leu Gln Val Ala Asn Ser Leu

865 870 875 880

Met Asn Gly Val Thr Leu Ser Thr Lys Leu Lys Asp Gly Val Asn Phe

885 890 895

Asn Val Asp Asp Ile Asn Phe Ser Pro Val Leu Gly Cys Leu Gly Ser

900 905 910

Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala Ile Glu Asp Leu Leu Phe

915 920 925

Asp Lys Val Lys Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn

930 935 940

Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu Ile Cys Val Gln Ser Tyr

945 950 955 960

Lys Gly Ile Lys Val Leu Pro Pro Leu Leu Ser Glu Asn Gln Ile Ser

965 970 975

Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser Leu Phe Pro Pro Trp Thr

980 985 990

Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn Val Gln Tyr Arg Ile Asn

995 1000 1005

Gly Leu Gly Val Thr Met Asp Val Leu Ser Gln Asn Gln Lys Leu Ile

1010 1015 1020

Ala Asn Ala Phe Asn Asn Ala Leu His Ala Ile Gln Gln Gly Phe Asp

1025 1030 1035 1040

Ala Thr Asn Ser Ala Leu Val Lys Ile Gln Ala Val Val Asn Ala Asn

1045 1050 1055

Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln Leu Ser Asn Arg Phe Gly

1060 1065 1070

Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Pro Pro

1075 1080 1085

Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala

1090 1095 1100

Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys

1105 1110 1115 1120

Phe Ser Ala Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser

1125 1130 1135

Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser

1140 1145 1150

Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr

1155 1160 1165

Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys Ile

1170 1175 1180

Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val Asn Val

1185 1190 1195 1200

Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr Pro Glu Pro

1205 1210 1215

Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys Ala Val Asn Tyr

1220 1225 1230

Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser Ile Pro Asn Leu Pro

1235 1240 1245

Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe Lys Asn Gln Thr Ser Val

1250 1255 1260

Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn Val Thr Phe Leu Asp Leu

1265 1270 1275 1280

Gln Val Glu Met Asn Arg Leu Gln Glu Ala Ile Lys Val Leu Asn His

1285 1290 1295

Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr Tyr Glu Tyr Tyr Val Lys

1300 1305 1310

Trp Pro Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met

1315 1320 1325

Leu Val Leu Leu Phe Phe Ile Ser Leu Trp Met Cys Ser Asn Gly Ser

1330 1335 1340

Leu Gln Cys Arg Ile Cys Ile

1345 1350

<210> 145

<211> 1348

<212> PRT

<213> artificial sequence

<220>

<223> PDI-OC43-H5iCT(V4)-AA

<400> 145

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Ile Gly Asp Leu Asn Cys Thr

20 25 30

Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn Asn Arg Asp Thr Gly Pro

35 40 45

Pro Ser Ile Ser Ile Asp Thr Val Asp Val Thr Asn Gly Leu Gly Thr

50 55 60

Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn Thr Thr Leu Phe Leu Asn

65 70 75 80

Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr Arg Asn Met Ala Leu Lys

85 90 95

Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe Lys Pro Pro Phe Leu Ser

100 105 110

Asp Phe Ile Asn Gly Ile Phe Ala Lys Val Lys Asn Thr Lys Val Phe

115 120 125

Lys Asp Gly Val Met Tyr Ser Glu Phe Pro Ala Ile Thr Ile Gly Ser

130 135 140

Thr Phe Val Asn Thr Ser Tyr Ser Val Val Val Gln Pro Arg Thr Ile

145 150 155 160

Asn Ser Thr Gln Asp Gly Val Asn Lys Leu Gln Gly Leu Leu Glu Val

165 170 175

Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr Pro His Thr Ile Cys His

180 185 190

Pro Asn Leu Gly Asn His Phe Lys Glu Leu Trp His Tyr Asp Thr Gly

195 200 205

Val Val Ser Cys Leu Tyr Lys Arg Asn Phe Thr Tyr Asp Val Asn Ala

210 215 220

Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu Gly Gly Thr Phe Tyr Ala

225 230 235 240

Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys Phe Leu Phe Asn Val Tyr

245 250 255

Leu Gly Met Ala Leu Ser His Tyr Tyr Val Met Pro Leu Thr Cys Ile

260 265 270

Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu Tyr Trp Val Thr Pro Leu

275 280 285

Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn Gln Asp Gly Ile Ile Phe

290 295 300

Asn Ala Val Asp Cys Met Ser Asp Phe Met Ser Glu Ile Lys Cys Lys

305 310 315 320

Thr Gln Ser Ile Ala Pro Pro Thr Gly Val Tyr Glu Leu Asn Gly Tyr

325 330 335

Thr Val Gln Pro Val Ala Asp Val Tyr Arg Arg Lys Pro Asp Leu Pro

340 345 350

Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp Lys Ser Val Pro Ser Pro

355 360 365

Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn Cys Asn Phe Asn Met Ser

370 375 380

Ser Leu Met Ser Phe Ile Gln Ala Asp Ser Phe Thr Cys Asn Asn Ile

385 390 395 400

Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe Ser Ser Ile Thr Ile Asp

405 410 415

Lys Phe Ala Ile Pro Asn Arg Arg Lys Val Asp Leu Gln Leu Gly Asn

420 425 430

Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg Ile Asp Thr Thr Ala Thr

435 440 445

Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala Ala Asn Val Ser Val Ser

450 455 460

Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg Phe Gly Phe Ile Glu Asp

465 470 475 480

Ser Val Phe Val Pro Gln Pro Thr Gly Val Phe Thr Asn His Ser Val

485 490 495

Val Tyr Ala Gln His Cys Phe Lys Ala Pro Lys Asn Phe Cys Pro Cys

500 505 510

Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn Gly Ile Gly Thr Cys Pro

515 520 525

Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn Leu Cys Thr Leu Asp Pro

530 535 540

Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys Cys Pro Gln Ser Lys Ser

545 550 555 560

Leu Val Gly Ile Gly Glu His Cys Ser Gly Leu Ala Val Lys Ser Asp

565 570 575

Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln Pro Gln Ala Phe Leu Gly

580 585 590

Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp Lys Cys Asn Ile Phe Ala

595 600 605

Asn Phe Ile Leu His Asp Val Asn Asn Gly Leu Thr Cys Ser Thr Asp

610 615 620

Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu Gly Val Cys Val Asn Tyr

625 630 635 640

Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile Phe Val Glu Val Asn Ala

645 650 655

Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn

660 665 670

Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn Arg Thr Phe Met Ile His

675 680 685

Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala Tyr His Ala Asn Ser Ser

690 695 700

Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys Cys Asn Tyr Val Phe Asn

705 710 715 720

Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile Asn Tyr Ser Phe Asp Ser

725 730 735

Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn Ser Thr Ala Ile Ser Val

740 745 750

Gln Thr Cys Asp Leu Thr Val Gly Ser Gly Tyr Cys Val Asp Tyr Ser

755 760 765

Lys Asn Gly Gly Ser Gly Ser Ala Ile Thr Thr Gly Tyr Arg Phe Thr

770 775 780

Asn Phe Glu Pro Phe Thr Val Asn Ser Val Asn Asp Ser Leu Glu Pro

785 790 795 800

Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro Ser Glu Phe Thr Ile Gly

805 810 815

Asn Met Glu Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp

820 825 830

Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala Ala Cys Lys Leu Gln Leu

835 840 845

Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile Asn Ala Ile Leu Thr Glu

850 855 860

Val Asn Glu Leu Leu Asp Thr Thr Gln Leu Gln Val Ala Asn Ser Leu

865 870 875 880

Met Asn Gly Val Thr Leu Ser Thr Lys Leu Lys Asp Gly Val Asn Phe

885 890 895

Asn Val Asp Asp Ile Asn Phe Ser Pro Val Leu Gly Cys Leu Gly Ser

900 905 910

Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala Ile Glu Asp Leu Leu Phe

915 920 925

Asp Lys Val Lys Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn

930 935 940

Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu Ile Cys Val Gln Ser Tyr

945 950 955 960

Lys Gly Ile Lys Val Leu Pro Pro Leu Leu Ser Glu Asn Gln Ile Ser

965 970 975

Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser Leu Phe Pro Pro Trp Thr

980 985 990

Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn Val Gln Tyr Arg Ile Asn

995 1000 1005

Gly Leu Gly Val Thr Met Asp Val Leu Ser Gln Asn Gln Lys Leu Ile

1010 1015 1020

Ala Asn Ala Phe Asn Asn Ala Leu His Ala Ile Gln Gln Gly Phe Asp

1025 1030 1035 1040

Ala Thr Asn Ser Ala Leu Val Lys Ile Gln Ala Val Val Asn Ala Asn

1045 1050 1055

Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln Leu Ser Asn Arg Phe Gly

1060 1065 1070

Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Pro Pro

1075 1080 1085

Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala

1090 1095 1100

Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys

1105 1110 1115 1120

Phe Ser Ala Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser

1125 1130 1135

Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser

1140 1145 1150

Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr

1155 1160 1165

Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys Ile

1170 1175 1180

Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val Asn Val

1185 1190 1195 1200

Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr Pro Glu Pro

1205 1210 1215

Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys Ala Val Asn Tyr

1220 1225 1230

Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser Ile Pro Asn Leu Pro

1235 1240 1245

Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe Lys Asn Gln Thr Ser Val

1250 1255 1260

Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn Val Thr Phe Leu Asp Leu

1265 1270 1275 1280

Gln Val Glu Met Asn Arg Leu Gln Glu Ala Ile Lys Val Leu Asn His

1285 1290 1295

Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr Tyr Glu Tyr Tyr Val Lys

1300 1305 1310

Trp Pro Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met

1315 1320 1325

Leu Val Leu Leu Phe Phe Ile Cys Cys Ser Asn Gly Ser Leu Gln Cys

1330 1335 1340

Arg Ile Cys Ile

1345

<210> 146

<211> 1351

<212> PRT

<213> artificial sequence

<220>

<223> PDI-OC43-H1cCT-AA

<400> 146

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Val Ile Gly Asp Leu Asn Cys Thr

20 25 30

Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn Asn Arg Asp Thr Gly Pro

35 40 45

Pro Ser Ile Ser Ile Asp Thr Val Asp Val Thr Asn Gly Leu Gly Thr

50 55 60

Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn Thr Thr Leu Phe Leu Asn

65 70 75 80

Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr Arg Asn Met Ala Leu Lys

85 90 95

Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe Lys Pro Pro Phe Leu Ser

100 105 110

Asp Phe Ile Asn Gly Ile Phe Ala Lys Val Lys Asn Thr Lys Val Phe

115 120 125

Lys Asp Gly Val Met Tyr Ser Glu Phe Pro Ala Ile Thr Ile Gly Ser

130 135 140

Thr Phe Val Asn Thr Ser Tyr Ser Val Val Val Gln Pro Arg Thr Ile

145 150 155 160

Asn Ser Thr Gln Asp Gly Val Asn Lys Leu Gln Gly Leu Leu Glu Val

165 170 175

Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr Pro His Thr Ile Cys His

180 185 190

Pro Asn Leu Gly Asn His Phe Lys Glu Leu Trp His Tyr Asp Thr Gly

195 200 205

Val Val Ser Cys Leu Tyr Lys Arg Asn Phe Thr Tyr Asp Val Asn Ala

210 215 220

Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu Gly Gly Thr Phe Tyr Ala

225 230 235 240

Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys Phe Leu Phe Asn Val Tyr

245 250 255

Leu Gly Met Ala Leu Ser His Tyr Tyr Val Met Pro Leu Thr Cys Ile

260 265 270

Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu Tyr Trp Val Thr Pro Leu

275 280 285

Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn Gln Asp Gly Ile Ile Phe

290 295 300

Asn Ala Val Asp Cys Met Ser Asp Phe Met Ser Glu Ile Lys Cys Lys

305 310 315 320

Thr Gln Ser Ile Ala Pro Pro Thr Gly Val Tyr Glu Leu Asn Gly Tyr

325 330 335

Thr Val Gln Pro Val Ala Asp Val Tyr Arg Arg Lys Pro Asp Leu Pro

340 345 350

Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp Lys Ser Val Pro Ser Pro

355 360 365

Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn Cys Asn Phe Asn Met Ser

370 375 380

Ser Leu Met Ser Phe Ile Gln Ala Asp Ser Phe Thr Cys Asn Asn Ile

385 390 395 400

Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe Ser Ser Ile Thr Ile Asp

405 410 415

Lys Phe Ala Ile Pro Asn Arg Arg Lys Val Asp Leu Gln Leu Gly Asn

420 425 430

Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg Ile Asp Thr Thr Ala Thr

435 440 445

Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala Ala Asn Val Ser Val Ser

450 455 460

Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg Phe Gly Phe Ile Glu Asp

465 470 475 480

Ser Val Phe Val Pro Gln Pro Thr Gly Val Phe Thr Asn His Ser Val

485 490 495

Val Tyr Ala Gln His Cys Phe Lys Ala Pro Lys Asn Phe Cys Pro Cys

500 505 510

Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn Gly Ile Gly Thr Cys Pro

515 520 525

Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn Leu Cys Thr Leu Asp Pro

530 535 540

Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys Cys Pro Gln Ser Lys Ser

545 550 555 560

Leu Val Gly Ile Gly Glu His Cys Ser Gly Leu Ala Val Lys Ser Asp

565 570 575

Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln Pro Gln Ala Phe Leu Gly

580 585 590

Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp Lys Cys Asn Ile Phe Ala

595 600 605

Asn Phe Ile Leu His Asp Val Asn Asn Gly Leu Thr Cys Ser Thr Asp

610 615 620

Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu Gly Val Cys Val Asn Tyr

625 630 635 640

Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile Phe Val Glu Val Asn Ala

645 650 655

Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu Tyr Asp Ser Asn Gly Asn

660 665 670

Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn Arg Thr Phe Met Ile His

675 680 685

Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala Tyr His Ala Asn Ser Ser

690 695 700

Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys Cys Asn Tyr Val Phe Asn

705 710 715 720

Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile Asn Tyr Ser Phe Asp Ser

725 730 735

Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn Ser Thr Ala Ile Ser Val

740 745 750

Gln Thr Cys Asp Leu Thr Val Gly Ser Gly Tyr Cys Val Asp Tyr Ser

755 760 765

Lys Asn Gly Gly Ser Gly Ser Ala Ile Thr Thr Gly Tyr Arg Phe Thr

770 775 780

Asn Phe Glu Pro Phe Thr Val Asn Ser Val Asn Asp Ser Leu Glu Pro

785 790 795 800

Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro Ser Glu Phe Thr Ile Gly

805 810 815

Asn Met Glu Glu Phe Ile Gln Thr Ser Ser Pro Lys Val Thr Ile Asp

820 825 830

Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala Ala Cys Lys Leu Gln Leu

835 840 845

Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile Asn Ala Ile Leu Thr Glu

850 855 860

Val Asn Glu Leu Leu Asp Thr Thr Gln Leu Gln Val Ala Asn Ser Leu

865 870 875 880

Met Asn Gly Val Thr Leu Ser Thr Lys Leu Lys Asp Gly Val Asn Phe

885 890 895

Asn Val Asp Asp Ile Asn Phe Ser Pro Val Leu Gly Cys Leu Gly Ser

900 905 910

Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala Ile Glu Asp Leu Leu Phe

915 920 925

Asp Lys Val Lys Leu Ser Asp Val Gly Phe Val Glu Ala Tyr Asn Asn

930 935 940

Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu Ile Cys Val Gln Ser Tyr

945 950 955 960

Lys Gly Ile Lys Val Leu Pro Pro Leu Leu Ser Glu Asn Gln Ile Ser

965 970 975

Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser Leu Phe Pro Pro Trp Thr

980 985 990

Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn Val Gln Tyr Arg Ile Asn

995 1000 1005

Gly Leu Gly Val Thr Met Asp Val Leu Ser Gln Asn Gln Lys Leu Ile

1010 1015 1020

Ala Asn Ala Phe Asn Asn Ala Leu His Ala Ile Gln Gln Gly Phe Asp

1025 1030 1035 1040

Ala Thr Asn Ser Ala Leu Val Lys Ile Gln Ala Val Val Asn Ala Asn

1045 1050 1055

Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln Leu Ser Asn Arg Phe Gly

1060 1065 1070

Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu Ser Arg Leu Asp Pro Pro

1075 1080 1085

Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile Asn Gly Arg Leu Thr Ala

1090 1095 1100

Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser Asp Ser Thr Leu Val Lys

1105 1110 1115 1120

Phe Ser Ala Ala Gln Ala Met Glu Lys Val Asn Glu Cys Val Lys Ser

1125 1130 1135

Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn Gly Asn His Ile Ile Ser

1140 1145 1150

Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr Phe Ile His Phe Asn Tyr

1155 1160 1165

Val Pro Thr Lys Tyr Val Thr Ala Lys Val Ser Pro Gly Leu Cys Ile

1170 1175 1180

Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser Gly Tyr Phe Val Asn Val

1185 1190 1195 1200

Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly Tyr Tyr Tyr Pro Glu Pro

1205 1210 1215

Ile Thr Glu Asn Asn Val Val Val Met Ser Thr Cys Ala Val Asn Tyr

1220 1225 1230

Thr Lys Ala Pro Tyr Val Met Leu Asn Thr Ser Ile Pro Asn Leu Pro

1235 1240 1245

Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe Lys Asn Gln Thr Ser Val

1250 1255 1260

Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn Val Thr Phe Leu Asp Leu

1265 1270 1275 1280

Gln Val Glu Met Asn Arg Leu Gln Glu Ala Ile Lys Val Leu Asn His

1285 1290 1295

Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr Tyr Glu Tyr Tyr Val Lys

1300 1305 1310

Trp Pro Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met

1315 1320 1325

Leu Val Leu Leu Phe Phe Ile Ser Phe Trp Met Cys Ser Asn Gly Ser

1330 1335 1340

Leu Gln Cys Arg Ile Cys Ile

1345 1350

<210> 147

<211> 48

<212> DNA

<213> artificial sequence

<220>

<223> IF(CoV229EwtCT).r

<400> 147

acgacacgac taaggccttc actgtatgtg gatcttttcg acatcgta 48

<210> 148

<211> 3546

<212> DNA

<213> artificial sequence

<220>

<223> PDI-229E -wtTMCT-DNA

<400> 148

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgcaaacgac taatgggctg aacaccagtt acagcgtctg taacggctgc 120

gtcggatata gcgagaacgt gttcgcagtg gaaagtgggg ggtacattcc ttccgacttc 180

gctttcaata actggtttct cctgactaac acaagctccg tcgtggatgg cgtggtcagg 240

tcctttcagc ctcttctcct gaattgcctg tggtctgtgt ccgggttaag attcactaca 300

ggcttcgtat acttcaacgg gacgggccgg ggggattgca agggcttctc ctccgacgtg 360

ctgtcagatg tgatccgtta caatctgaac ttcgaagaga acttacggcg ggggacaatc 420

ctgttcaaaa catcatatgg cgtagtcgta ttttactgca ccaataatac cctggtgagt 480

ggggacgccc atattccctt cggaacagtg ctgggtaact tttactgttt tgtcaacact 540

acgatcggaa acgaaaccac tagcgccttt gtcggagctc tgccaaaaac agttagggag 600

ttcgtgatct ctcggaccgg tcacttctat atcaacggct accgttattt tactttgggc 660

aacgtcgaag ccgtcaattt taatgtgaca actgcagaga caactgactt ttgcactgtg 720

gctctcgcca gttatgccga tgtgctggtg aatgtaagtc aaacgtcaat tgccaacatc 780

atctattgta actcagtaat caaccggctc cgctgtgacc aactctcatt cgacgtcccc 840

gacggattct attccacgag cccgattcag agcgtggaac tgccagtttc catcgtatcc 900

ctcccagttt accacaagca cacttttatc gttctctacg tagattttaa accccagtca 960

ggaggaggga aatgcttcaa ctgctacccg gctggcgtga acatcacctt ggccaatttt 1020

aatgaaacta aagggcccct ttgcgtggat acgtcacact ttaccacaaa gtatgttgca 1080

gtctatgcta acgtcggcag gtggtcagcg tccattaaca caggcaattg cccgttctct 1140

ttcgggaaag tgaacaactt cgtgaagttt ggaagtgtgt gcttcagttt gaaagacatt 1200

ccgggcggct gcgccatgcc tattgtggct aattgggctt attccaagta ctacaccatt 1260

ggctctctct acgttagctg gagcgacggt gacggtataa cgggcgtacc acaaccggtg 1320

gaaggggtca gctctttcat gaatgtcact ctggacaagt gtaccaaata taatatatac 1380

gatgtgagtg gagtgggcgt tatacgcgtg tctaacgaca cctttctaaa cggcataacc 1440

tacacaagca cgtcaggcaa tctgttaggt tttaaagacg tcactaaagg cactatatat 1500

agcatcaccc catgcaaccc acctgatcaa ttagtcgtat atcagcaagc tgttgtgggt 1560

gctatgctgt cagaaaactt caccagctac gggttctcca atgtggtgga actgcccaaa 1620

ttcttttacg ctagcaatgg cacatataac tgtactgacg ccgtcttgac ttacagttca 1680

ttcggagtgt gcgcggacgg cagcattatc gccgtgcagc cggccaatgt cagctatgat 1740

tccgtttccg ccatcgtgac agccaacttg tcgattccct ctaactggac aacgtctgtc 1800

caagtcgaat atctgcagat cacctcaacc cccatagtag tcgattgctc aacctacgtc 1860

tgcaacggta atgtcagatg tgtcgagctg ctcaagcagt acacctccgc ctgtaagact 1920

attgaggatg cattaagaaa tagtgcaaga ttggaaagcg ccgatgtgtc ggaaatgcta 1980

accttcgata agaaggcatt cacactggcg aacgtaagct ctttcggcga ttacaacctg 2040

tcttcggtaa tccctagctt gcccacatcc ggctctcggg tggcggggcg gagcgctatc 2100

gaggacattt tattctcgaa actggttaca tctgggctcg gaactgtgga cgccgattac 2160

aagaagtgca ccaagggcct aagcatcgcc gacctcgcct gtgctcagta ctacaacgga 2220

attatggtgc tgccaggtgt cgctgacgca gagcggatgg ctatgtatac cggcagtctc 2280

attggcggga ttgcgttggg cggcctgacg tccgctgtct ccatcccttt ctctctggct 2340

atacaagccc gactgaatta tgtggccctg cagactgatg tcctgcaaga aaatcagaag 2400

attcttgccg ccagcttcaa caaggccatg actaatattg tggatgcgtt taccggagtg 2460

aatgacgcca tcacccaaac gtcccaagcc ctgcagacag tcgccacggc gttaaacaaa 2520

atccaggatg tagtgaatca gcaagggaac agcttgaatc acctgacgtc ccagttaaga 2580

cagaactttc aggcaatcag tagctcaatc caggctatct acgatcgatt agatcctcct 2640

caggcagatc agcaggtgga tcggctcatc accggccgcc tcgcggcatt gaatgttttc 2700

gtaagtcata ccttgaccaa gtacacggag gtgagggcca gtcgccagct ggctcagcaa 2760

aaagtgaatg agtgtgtgaa atcacagagc aaacggtacg ggttttgtgg aaatgggacg 2820

cacatcttta gcatcgttaa tgctgccccc gaagggttag tcttcctgca cactgtgctc 2880

cttcctaccc agtataaaga tgtcgaagca tggtctgggc tctgtgtcga tggaactaac 2940

ggttatgtcc ttcgacagcc aaacctcgct ctctataaag aagggaatta ctataggatc 3000

acctcaagaa tcatgttcga gcccaggata ccaacaatgg ccgattttgt gcagattgaa 3060

aattgtaacg tgacctttgt gaatatcagt cgatccgagc ttcaaacgat tgttcctgag 3120

tacatcgacg tgaataaaac tctacaagag ctgtcctata aactgcctaa ttataccgtg 3180

cctgaccttg tagtcgagca atacaaccag actattctga acctgacatc ggaaatctct 3240

acattggaga ataaaagcgc cgagctcaat tacacagtgc agaagctgca gaccctgatc 3300

gacaatatta acagcactct tgtggactta aagtggctga accgtgtgga gacttacatc 3360

aagtggccct ggtgggtgtg gctctgtatt tccgtggtcc ttatatttgt tgtaagtatg 3420

ctgctcctgt gctgttgctc aaccgggtgc tgcggttttt tctcctgttt cgcctcatcc 3480

atccgtggct gttgtgagag cactaaactg ccatattacg atgtcgaaaa gatccacata 3540

cagtga 3546

<210> 149

<211> 3492

<212> DNA

<213> artificial sequence

<220>

<223> PDI-229E -H5iTMCT-DNA

<400> 149

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgcaaacgac taatgggctg aacaccagtt acagcgtctg taacggctgc 120

gtcggatata gcgagaacgt gttcgcagtg gaaagtgggg ggtacattcc ttccgacttc 180

gctttcaata actggtttct cctgactaac acaagctccg tcgtggatgg cgtggtcagg 240

tcctttcagc ctcttctcct gaattgcctg tggtctgtgt ccgggttaag attcactaca 300

ggcttcgtat acttcaacgg gacgggccgg ggggattgca agggcttctc ctccgacgtg 360

ctgtcagatg tgatccgtta caatctgaac ttcgaagaga acttacggcg ggggacaatc 420

ctgttcaaaa catcatatgg cgtagtcgta ttttactgca ccaataatac cctggtgagt 480

ggggacgccc atattccctt cggaacagtg ctgggtaact tttactgttt tgtcaacact 540

acgatcggaa acgaaaccac tagcgccttt gtcggagctc tgccaaaaac agttagggag 600

ttcgtgatct ctcggaccgg tcacttctat atcaacggct accgttattt tactttgggc 660

aacgtcgaag ccgtcaattt taatgtgaca actgcagaga caactgactt ttgcactgtg 720

gctctcgcca gttatgccga tgtgctggtg aatgtaagtc aaacgtcaat tgccaacatc 780

atctattgta actcagtaat caaccggctc cgctgtgacc aactctcatt cgacgtcccc 840

gacggattct attccacgag cccgattcag agcgtggaac tgccagtttc catcgtatcc 900

ctcccagttt accacaagca cacttttatc gttctctacg tagattttaa accccagtca 960

ggaggaggga aatgcttcaa ctgctacccg gctggcgtga acatcacctt ggccaatttt 1020

aatgaaacta aagggcccct ttgcgtggat acgtcacact ttaccacaaa gtatgttgca 1080

gtctatgcta acgtcggcag gtggtcagcg tccattaaca caggcaattg cccgttctct 1140

ttcgggaaag tgaacaactt cgtgaagttt ggaagtgtgt gcttcagttt gaaagacatt 1200

ccgggcggct gcgccatgcc tattgtggct aattgggctt attccaagta ctacaccatt 1260

ggctctctct acgttagctg gagcgacggt gacggtataa cgggcgtacc acaaccggtg 1320

gaaggggtca gctctttcat gaatgtcact ctggacaagt gtaccaaata taatatatac 1380

gatgtgagtg gagtgggcgt tatacgcgtg tctaacgaca cctttctaaa cggcataacc 1440

tacacaagca cgtcaggcaa tctgttaggt tttaaagacg tcactaaagg cactatatat 1500

agcatcaccc catgcaaccc acctgatcaa ttagtcgtat atcagcaagc tgttgtgggt 1560

gctatgctgt cagaaaactt caccagctac gggttctcca atgtggtgga actgcccaaa 1620

ttcttttacg ctagcaatgg cacatataac tgtactgacg ccgtcttgac ttacagttca 1680

ttcggagtgt gcgcggacgg cagcattatc gccgtgcagc cggccaatgt cagctatgat 1740

tccgtttccg ccatcgtgac agccaacttg tcgattccct ctaactggac aacgtctgtc 1800

caagtcgaat atctgcagat cacctcaacc cccatagtag tcgattgctc aacctacgtc 1860

tgcaacggta atgtcagatg tgtcgagctg ctcaagcagt acacctccgc ctgtaagact 1920

attgaggatg cattaagaaa tagtgcaaga ttggaaagcg ccgatgtgtc ggaaatgcta 1980

accttcgata agaaggcatt cacactggcg aacgtaagct ctttcggcga ttacaacctg 2040

tcttcggtaa tccctagctt gcccacatcc ggctctcggg tggcggggcg gagcgctatc 2100

gaggacattt tattctcgaa actggttaca tctgggctcg gaactgtgga cgccgattac 2160

aagaagtgca ccaagggcct aagcatcgcc gacctcgcct gtgctcagta ctacaacgga 2220

attatggtgc tgccaggtgt cgctgacgca gagcggatgg ctatgtatac cggcagtctc 2280

attggcggga ttgcgttggg cggcctgacg tccgctgtct ccatcccttt ctctctggct 2340

atacaagccc gactgaatta tgtggccctg cagactgatg tcctgcaaga aaatcagaag 2400

attcttgccg ccagcttcaa caaggccatg actaatattg tggatgcgtt taccggagtg 2460

aatgacgcca tcacccaaac gtcccaagcc ctgcagacag tcgccacggc gttaaacaaa 2520

atccaggatg tagtgaatca gcaagggaac agcttgaatc acctgacgtc ccagttaaga 2580

cagaactttc aggcaatcag tagctcaatc caggctatct acgatcgatt agatcctcct 2640

caggcagatc agcaggtgga tcggctcatc accggccgcc tcgcggcatt gaatgttttc 2700

gtaagtcata ccttgaccaa gtacacggag gtgagggcca gtcgccagct ggctcagcaa 2760

aaagtgaatg agtgtgtgaa atcacagagc aaacggtacg ggttttgtgg aaatgggacg 2820

cacatcttta gcatcgttaa tgctgccccc gaagggttag tcttcctgca cactgtgctc 2880

cttcctaccc agtataaaga tgtcgaagca tggtctgggc tctgtgtcga tggaactaac 2940

ggttatgtcc ttcgacagcc aaacctcgct ctctataaag aagggaatta ctataggatc 3000

acctcaagaa tcatgttcga gcccaggata ccaacaatgg ccgattttgt gcagattgaa 3060

aattgtaacg tgacctttgt gaatatcagt cgatccgagc ttcaaacgat tgttcctgag 3120

tacatcgacg tgaataaaac tctacaagag ctgtcctata aactgcctaa ttataccgtg 3180

cctgaccttg tagtcgagca atacaaccag actattctga acctgacatc ggaaatctct 3240

acattggaga ataaaagcgc cgagctcaat tacacagtgc agaagctgca gaccctgatc 3300

gacaatatta acagcactct tgtggactta aagtggctga accgtgtgga gacttacatc 3360

aagtggccct ggtggcaaat actgtcaatt tattcaacag tggcgagttc cctagcactg 3420

gcaatcatga tggctggtct atctttatgg atgtgctcca atggatcgtt acaatgcaga 3480

atttgcattt ga 3492

<210> 150

<211> 3480

<212> DNA

<213> artificial sequence

<220>

<223> PDI-229E -H5iCT-DNA

<400> 150

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgcaaacgac taatgggctg aacaccagtt acagcgtctg taacggctgc 120

gtcggatata gcgagaacgt gttcgcagtg gaaagtgggg ggtacattcc ttccgacttc 180

gctttcaata actggtttct cctgactaac acaagctccg tcgtggatgg cgtggtcagg 240

tcctttcagc ctcttctcct gaattgcctg tggtctgtgt ccgggttaag attcactaca 300

ggcttcgtat acttcaacgg gacgggccgg ggggattgca agggcttctc ctccgacgtg 360

ctgtcagatg tgatccgtta caatctgaac ttcgaagaga acttacggcg ggggacaatc 420

ctgttcaaaa catcatatgg cgtagtcgta ttttactgca ccaataatac cctggtgagt 480

ggggacgccc atattccctt cggaacagtg ctgggtaact tttactgttt tgtcaacact 540

acgatcggaa acgaaaccac tagcgccttt gtcggagctc tgccaaaaac agttagggag 600

ttcgtgatct ctcggaccgg tcacttctat atcaacggct accgttattt tactttgggc 660

aacgtcgaag ccgtcaattt taatgtgaca actgcagaga caactgactt ttgcactgtg 720

gctctcgcca gttatgccga tgtgctggtg aatgtaagtc aaacgtcaat tgccaacatc 780

atctattgta actcagtaat caaccggctc cgctgtgacc aactctcatt cgacgtcccc 840

gacggattct attccacgag cccgattcag agcgtggaac tgccagtttc catcgtatcc 900

ctcccagttt accacaagca cacttttatc gttctctacg tagattttaa accccagtca 960

ggaggaggga aatgcttcaa ctgctacccg gctggcgtga acatcacctt ggccaatttt 1020

aatgaaacta aagggcccct ttgcgtggat acgtcacact ttaccacaaa gtatgttgca 1080

gtctatgcta acgtcggcag gtggtcagcg tccattaaca caggcaattg cccgttctct 1140

ttcgggaaag tgaacaactt cgtgaagttt ggaagtgtgt gcttcagttt gaaagacatt 1200

ccgggcggct gcgccatgcc tattgtggct aattgggctt attccaagta ctacaccatt 1260

ggctctctct acgttagctg gagcgacggt gacggtataa cgggcgtacc acaaccggtg 1320

gaaggggtca gctctttcat gaatgtcact ctggacaagt gtaccaaata taatatatac 1380

gatgtgagtg gagtgggcgt tatacgcgtg tctaacgaca cctttctaaa cggcataacc 1440

tacacaagca cgtcaggcaa tctgttaggt tttaaagacg tcactaaagg cactatatat 1500

agcatcaccc catgcaaccc acctgatcaa ttagtcgtat atcagcaagc tgttgtgggt 1560

gctatgctgt cagaaaactt caccagctac gggttctcca atgtggtgga actgcccaaa 1620

ttcttttacg ctagcaatgg cacatataac tgtactgacg ccgtcttgac ttacagttca 1680

ttcggagtgt gcgcggacgg cagcattatc gccgtgcagc cggccaatgt cagctatgat 1740

tccgtttccg ccatcgtgac agccaacttg tcgattccct ctaactggac aacgtctgtc 1800

caagtcgaat atctgcagat cacctcaacc cccatagtag tcgattgctc aacctacgtc 1860

tgcaacggta atgtcagatg tgtcgagctg ctcaagcagt acacctccgc ctgtaagact 1920

attgaggatg cattaagaaa tagtgcaaga ttggaaagcg ccgatgtgtc ggaaatgcta 1980

accttcgata agaaggcatt cacactggcg aacgtaagct ctttcggcga ttacaacctg 2040

tcttcggtaa tccctagctt gcccacatcc ggctctcggg tggcggggcg gagcgctatc 2100

gaggacattt tattctcgaa actggttaca tctgggctcg gaactgtgga cgccgattac 2160

aagaagtgca ccaagggcct aagcatcgcc gacctcgcct gtgctcagta ctacaacgga 2220

attatggtgc tgccaggtgt cgctgacgca gagcggatgg ctatgtatac cggcagtctc 2280

attggcggga ttgcgttggg cggcctgacg tccgctgtct ccatcccttt ctctctggct 2340

atacaagccc gactgaatta tgtggccctg cagactgatg tcctgcaaga aaatcagaag 2400

attcttgccg ccagcttcaa caaggccatg actaatattg tggatgcgtt taccggagtg 2460

aatgacgcca tcacccaaac gtcccaagcc ctgcagacag tcgccacggc gttaaacaaa 2520

atccaggatg tagtgaatca gcaagggaac agcttgaatc acctgacgtc ccagttaaga 2580

cagaactttc aggcaatcag tagctcaatc caggctatct acgatcgatt agatcctcct 2640

caggcagatc agcaggtgga tcggctcatc accggccgcc tcgcggcatt gaatgttttc 2700

gtaagtcata ccttgaccaa gtacacggag gtgagggcca gtcgccagct ggctcagcaa 2760

aaagtgaatg agtgtgtgaa atcacagagc aaacggtacg ggttttgtgg aaatgggacg 2820

cacatcttta gcatcgttaa tgctgccccc gaagggttag tcttcctgca cactgtgctc 2880

cttcctaccc agtataaaga tgtcgaagca tggtctgggc tctgtgtcga tggaactaac 2940

ggttatgtcc ttcgacagcc aaacctcgct ctctataaag aagggaatta ctataggatc 3000

acctcaagaa tcatgttcga gcccaggata ccaacaatgg ccgattttgt gcagattgaa 3060

aattgtaacg tgacctttgt gaatatcagt cgatccgagc ttcaaacgat tgttcctgag 3120

tacatcgacg tgaataaaac tctacaagag ctgtcctata aactgcctaa ttataccgtg 3180

cctgaccttg tagtcgagca atacaaccag actattctga acctgacatc ggaaatctct 3240

acattggaga ataaaagcgc cgagctcaat tacacagtgc agaagctgca gaccctgatc 3300

gacaatatta acagcactct tgtggactta aagtggctga accgtgtgga gacttacatc 3360

aagtggccct ggtgggtgtg gctctgtatt tccgtggtcc ttatatttgt tgtaagtatg 3420

ctgctcctgt ctttatggat gtgctccaat ggatcgttac aatgcagaat ttgcatttga 3480

<210> 151

<211> 3471

<212> DNA

<213> artificial sequence

<220>

<223> PDI-229E -H5iCT(V4)-DNA

<400> 151

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgcaaacgac taatgggctg aacaccagtt acagcgtctg taacggctgc 120

gtcggatata gcgagaacgt gttcgcagtg gaaagtgggg ggtacattcc ttccgacttc 180

gctttcaata actggtttct cctgactaac acaagctccg tcgtggatgg cgtggtcagg 240

tcctttcagc ctcttctcct gaattgcctg tggtctgtgt ccgggttaag attcactaca 300

ggcttcgtat acttcaacgg gacgggccgg ggggattgca agggcttctc ctccgacgtg 360

ctgtcagatg tgatccgtta caatctgaac ttcgaagaga acttacggcg ggggacaatc 420

ctgttcaaaa catcatatgg cgtagtcgta ttttactgca ccaataatac cctggtgagt 480

ggggacgccc atattccctt cggaacagtg ctgggtaact tttactgttt tgtcaacact 540

acgatcggaa acgaaaccac tagcgccttt gtcggagctc tgccaaaaac agttagggag 600

ttcgtgatct ctcggaccgg tcacttctat atcaacggct accgttattt tactttgggc 660

aacgtcgaag ccgtcaattt taatgtgaca actgcagaga caactgactt ttgcactgtg 720

gctctcgcca gttatgccga tgtgctggtg aatgtaagtc aaacgtcaat tgccaacatc 780

atctattgta actcagtaat caaccggctc cgctgtgacc aactctcatt cgacgtcccc 840

gacggattct attccacgag cccgattcag agcgtggaac tgccagtttc catcgtatcc 900

ctcccagttt accacaagca cacttttatc gttctctacg tagattttaa accccagtca 960

ggaggaggga aatgcttcaa ctgctacccg gctggcgtga acatcacctt ggccaatttt 1020

aatgaaacta aagggcccct ttgcgtggat acgtcacact ttaccacaaa gtatgttgca 1080

gtctatgcta acgtcggcag gtggtcagcg tccattaaca caggcaattg cccgttctct 1140

ttcgggaaag tgaacaactt cgtgaagttt ggaagtgtgt gcttcagttt gaaagacatt 1200

ccgggcggct gcgccatgcc tattgtggct aattgggctt attccaagta ctacaccatt 1260

ggctctctct acgttagctg gagcgacggt gacggtataa cgggcgtacc acaaccggtg 1320

gaaggggtca gctctttcat gaatgtcact ctggacaagt gtaccaaata taatatatac 1380

gatgtgagtg gagtgggcgt tatacgcgtg tctaacgaca cctttctaaa cggcataacc 1440

tacacaagca cgtcaggcaa tctgttaggt tttaaagacg tcactaaagg cactatatat 1500

agcatcaccc catgcaaccc acctgatcaa ttagtcgtat atcagcaagc tgttgtgggt 1560

gctatgctgt cagaaaactt caccagctac gggttctcca atgtggtgga actgcccaaa 1620

ttcttttacg ctagcaatgg cacatataac tgtactgacg ccgtcttgac ttacagttca 1680

ttcggagtgt gcgcggacgg cagcattatc gccgtgcagc cggccaatgt cagctatgat 1740

tccgtttccg ccatcgtgac agccaacttg tcgattccct ctaactggac aacgtctgtc 1800

caagtcgaat atctgcagat cacctcaacc cccatagtag tcgattgctc aacctacgtc 1860

tgcaacggta atgtcagatg tgtcgagctg ctcaagcagt acacctccgc ctgtaagact 1920

attgaggatg cattaagaaa tagtgcaaga ttggaaagcg ccgatgtgtc ggaaatgcta 1980

accttcgata agaaggcatt cacactggcg aacgtaagct ctttcggcga ttacaacctg 2040

tcttcggtaa tccctagctt gcccacatcc ggctctcggg tggcggggcg gagcgctatc 2100

gaggacattt tattctcgaa actggttaca tctgggctcg gaactgtgga cgccgattac 2160

aagaagtgca ccaagggcct aagcatcgcc gacctcgcct gtgctcagta ctacaacgga 2220

attatggtgc tgccaggtgt cgctgacgca gagcggatgg ctatgtatac cggcagtctc 2280

attggcggga ttgcgttggg cggcctgacg tccgctgtct ccatcccttt ctctctggct 2340

atacaagccc gactgaatta tgtggccctg cagactgatg tcctgcaaga aaatcagaag 2400

attcttgccg ccagcttcaa caaggccatg actaatattg tggatgcgtt taccggagtg 2460

aatgacgcca tcacccaaac gtcccaagcc ctgcagacag tcgccacggc gttaaacaaa 2520

atccaggatg tagtgaatca gcaagggaac agcttgaatc acctgacgtc ccagttaaga 2580

cagaactttc aggcaatcag tagctcaatc caggctatct acgatcgatt agatcctcct 2640

caggcagatc agcaggtgga tcggctcatc accggccgcc tcgcggcatt gaatgttttc 2700

gtaagtcata ccttgaccaa gtacacggag gtgagggcca gtcgccagct ggctcagcaa 2760

aaagtgaatg agtgtgtgaa atcacagagc aaacggtacg ggttttgtgg aaatgggacg 2820

cacatcttta gcatcgttaa tgctgccccc gaagggttag tcttcctgca cactgtgctc 2880

cttcctaccc agtataaaga tgtcgaagca tggtctgggc tctgtgtcga tggaactaac 2940

ggttatgtcc ttcgacagcc aaacctcgct ctctataaag aagggaatta ctataggatc 3000

acctcaagaa tcatgttcga gcccaggata ccaacaatgg ccgattttgt gcagattgaa 3060

aattgtaacg tgacctttgt gaatatcagt cgatccgagc ttcaaacgat tgttcctgag 3120

tacatcgacg tgaataaaac tctacaagag ctgtcctata aactgcctaa ttataccgtg 3180

cctgaccttg tagtcgagca atacaaccag actattctga acctgacatc ggaaatctct 3240

acattggaga ataaaagcgc cgagctcaat tacacagtgc agaagctgca gaccctgatc 3300

gacaatatta acagcactct tgtggactta aagtggctga accgtgtgga gacttacatc 3360

aagtggccct ggtgggtgtg gctctgtatt tccgtggtcc ttatatttgt tgtaagtatg 3420

ctgctcctgt gctgctccaa tggatcgtta caatgcagaa tttgcatttg a 3471

<210> 152

<211> 3480

<212> DNA

<213> artificial sequence

<220>

<223> PDI-229E -H1cCT-DNA

<400> 152

atggcgaaaa acgttgcgat tttcggctta ttgttttctc ttcttgtgtt ggttccttct 60

cagatcttcg cgcaaacgac taatgggctg aacaccagtt acagcgtctg taacggctgc 120

gtcggatata gcgagaacgt gttcgcagtg gaaagtgggg ggtacattcc ttccgacttc 180

gctttcaata actggtttct cctgactaac acaagctccg tcgtggatgg cgtggtcagg 240

tcctttcagc ctcttctcct gaattgcctg tggtctgtgt ccgggttaag attcactaca 300

ggcttcgtat acttcaacgg gacgggccgg ggggattgca agggcttctc ctccgacgtg 360

ctgtcagatg tgatccgtta caatctgaac ttcgaagaga acttacggcg ggggacaatc 420

ctgttcaaaa catcatatgg cgtagtcgta ttttactgca ccaataatac cctggtgagt 480

ggggacgccc atattccctt cggaacagtg ctgggtaact tttactgttt tgtcaacact 540

acgatcggaa acgaaaccac tagcgccttt gtcggagctc tgccaaaaac agttagggag 600

ttcgtgatct ctcggaccgg tcacttctat atcaacggct accgttattt tactttgggc 660

aacgtcgaag ccgtcaattt taatgtgaca actgcagaga caactgactt ttgcactgtg 720

gctctcgcca gttatgccga tgtgctggtg aatgtaagtc aaacgtcaat tgccaacatc 780

atctattgta actcagtaat caaccggctc cgctgtgacc aactctcatt cgacgtcccc 840

gacggattct attccacgag cccgattcag agcgtggaac tgccagtttc catcgtatcc 900

ctcccagttt accacaagca cacttttatc gttctctacg tagattttaa accccagtca 960

ggaggaggga aatgcttcaa ctgctacccg gctggcgtga acatcacctt ggccaatttt 1020

aatgaaacta aagggcccct ttgcgtggat acgtcacact ttaccacaaa gtatgttgca 1080

gtctatgcta acgtcggcag gtggtcagcg tccattaaca caggcaattg cccgttctct 1140

ttcgggaaag tgaacaactt cgtgaagttt ggaagtgtgt gcttcagttt gaaagacatt 1200

ccgggcggct gcgccatgcc tattgtggct aattgggctt attccaagta ctacaccatt 1260

ggctctctct acgttagctg gagcgacggt gacggtataa cgggcgtacc acaaccggtg 1320

gaaggggtca gctctttcat gaatgtcact ctggacaagt gtaccaaata taatatatac 1380

gatgtgagtg gagtgggcgt tatacgcgtg tctaacgaca cctttctaaa cggcataacc 1440

tacacaagca cgtcaggcaa tctgttaggt tttaaagacg tcactaaagg cactatatat 1500

agcatcaccc catgcaaccc acctgatcaa ttagtcgtat atcagcaagc tgttgtgggt 1560

gctatgctgt cagaaaactt caccagctac gggttctcca atgtggtgga actgcccaaa 1620

ttcttttacg ctagcaatgg cacatataac tgtactgacg ccgtcttgac ttacagttca 1680

ttcggagtgt gcgcggacgg cagcattatc gccgtgcagc cggccaatgt cagctatgat 1740

tccgtttccg ccatcgtgac agccaacttg tcgattccct ctaactggac aacgtctgtc 1800

caagtcgaat atctgcagat cacctcaacc cccatagtag tcgattgctc aacctacgtc 1860

tgcaacggta atgtcagatg tgtcgagctg ctcaagcagt acacctccgc ctgtaagact 1920

attgaggatg cattaagaaa tagtgcaaga ttggaaagcg ccgatgtgtc ggaaatgcta 1980

accttcgata agaaggcatt cacactggcg aacgtaagct ctttcggcga ttacaacctg 2040

tcttcggtaa tccctagctt gcccacatcc ggctctcggg tggcggggcg gagcgctatc 2100

gaggacattt tattctcgaa actggttaca tctgggctcg gaactgtgga cgccgattac 2160

aagaagtgca ccaagggcct aagcatcgcc gacctcgcct gtgctcagta ctacaacgga 2220

attatggtgc tgccaggtgt cgctgacgca gagcggatgg ctatgtatac cggcagtctc 2280

attggcggga ttgcgttggg cggcctgacg tccgctgtct ccatcccttt ctctctggct 2340

atacaagccc gactgaatta tgtggccctg cagactgatg tcctgcaaga aaatcagaag 2400

attcttgccg ccagcttcaa caaggccatg actaatattg tggatgcgtt taccggagtg 2460

aatgacgcca tcacccaaac gtcccaagcc ctgcagacag tcgccacggc gttaaacaaa 2520

atccaggatg tagtgaatca gcaagggaac agcttgaatc acctgacgtc ccagttaaga 2580

cagaactttc aggcaatcag tagctcaatc caggctatct acgatcgatt agatcctcct 2640

caggcagatc agcaggtgga tcggctcatc accggccgcc tcgcggcatt gaatgttttc 2700

gtaagtcata ccttgaccaa gtacacggag gtgagggcca gtcgccagct ggctcagcaa 2760

aaagtgaatg agtgtgtgaa atcacagagc aaacggtacg ggttttgtgg aaatgggacg 2820

cacatcttta gcatcgttaa tgctgccccc gaagggttag tcttcctgca cactgtgctc 2880

cttcctaccc agtataaaga tgtcgaagca tggtctgggc tctgtgtcga tggaactaac 2940

ggttatgtcc ttcgacagcc aaacctcgct ctctataaag aagggaatta ctataggatc 3000

acctcaagaa tcatgttcga gcccaggata ccaacaatgg ccgattttgt gcagattgaa 3060

aattgtaacg tgacctttgt gaatatcagt cgatccgagc ttcaaacgat tgttcctgag 3120

tacatcgacg tgaataaaac tctacaagag ctgtcctata aactgcctaa ttataccgtg 3180

cctgaccttg tagtcgagca atacaaccag actattctga acctgacatc ggaaatctct 3240

acattggaga ataaaagcgc cgagctcaat tacacagtgc agaagctgca gaccctgatc 3300

gacaatatta acagcactct tgtggactta aagtggctga accgtgtgga gacttacatc 3360

aagtggccct ggtgggtgtg gctctgtatt tccgtggtcc ttatatttgt tgtaagtatg 3420

ctgctcctga gcttctggat gtgctctaat gggtctctac agtgtagaat atgtatttga 3480

<210> 153

<211> 1181

<212> PRT

<213> artificial sequence

<220>

<223> PDI-229E -wtTMCT-AA

<400> 153

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Gln Thr Thr Asn Gly Leu Asn Thr

20 25 30

Ser Tyr Ser Val Cys Asn Gly Cys Val Gly Tyr Ser Glu Asn Val Phe

35 40 45

Ala Val Glu Ser Gly Gly Tyr Ile Pro Ser Asp Phe Ala Phe Asn Asn

50 55 60

Trp Phe Leu Leu Thr Asn Thr Ser Ser Val Val Asp Gly Val Val Arg

65 70 75 80

Ser Phe Gln Pro Leu Leu Leu Asn Cys Leu Trp Ser Val Ser Gly Leu

85 90 95

Arg Phe Thr Thr Gly Phe Val Tyr Phe Asn Gly Thr Gly Arg Gly Asp

100 105 110

Cys Lys Gly Phe Ser Ser Asp Val Leu Ser Asp Val Ile Arg Tyr Asn

115 120 125

Leu Asn Phe Glu Glu Asn Leu Arg Arg Gly Thr Ile Leu Phe Lys Thr

130 135 140

Ser Tyr Gly Val Val Val Phe Tyr Cys Thr Asn Asn Thr Leu Val Ser

145 150 155 160

Gly Asp Ala His Ile Pro Phe Gly Thr Val Leu Gly Asn Phe Tyr Cys

165 170 175

Phe Val Asn Thr Thr Ile Gly Asn Glu Thr Thr Ser Ala Phe Val Gly

180 185 190

Ala Leu Pro Lys Thr Val Arg Glu Phe Val Ile Ser Arg Thr Gly His

195 200 205

Phe Tyr Ile Asn Gly Tyr Arg Tyr Phe Thr Leu Gly Asn Val Glu Ala

210 215 220

Val Asn Phe Asn Val Thr Thr Ala Glu Thr Thr Asp Phe Cys Thr Val

225 230 235 240

Ala Leu Ala Ser Tyr Ala Asp Val Leu Val Asn Val Ser Gln Thr Ser

245 250 255

Ile Ala Asn Ile Ile Tyr Cys Asn Ser Val Ile Asn Arg Leu Arg Cys

260 265 270

Asp Gln Leu Ser Phe Asp Val Pro Asp Gly Phe Tyr Ser Thr Ser Pro

275 280 285

Ile Gln Ser Val Glu Leu Pro Val Ser Ile Val Ser Leu Pro Val Tyr

290 295 300

His Lys His Thr Phe Ile Val Leu Tyr Val Asp Phe Lys Pro Gln Ser

305 310 315 320

Gly Gly Gly Lys Cys Phe Asn Cys Tyr Pro Ala Gly Val Asn Ile Thr

325 330 335

Leu Ala Asn Phe Asn Glu Thr Lys Gly Pro Leu Cys Val Asp Thr Ser

340 345 350

His Phe Thr Thr Lys Tyr Val Ala Val Tyr Ala Asn Val Gly Arg Trp

355 360 365

Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro Phe Ser Phe Gly Lys Val

370 375 380

Asn Asn Phe Val Lys Phe Gly Ser Val Cys Phe Ser Leu Lys Asp Ile

385 390 395 400

Pro Gly Gly Cys Ala Met Pro Ile Val Ala Asn Trp Ala Tyr Ser Lys

405 410 415

Tyr Tyr Thr Ile Gly Ser Leu Tyr Val Ser Trp Ser Asp Gly Asp Gly

420 425 430

Ile Thr Gly Val Pro Gln Pro Val Glu Gly Val Ser Ser Phe Met Asn

435 440 445

Val Thr Leu Asp Lys Cys Thr Lys Tyr Asn Ile Tyr Asp Val Ser Gly

450 455 460

Val Gly Val Ile Arg Val Ser Asn Asp Thr Phe Leu Asn Gly Ile Thr

465 470 475 480

Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly Phe Lys Asp Val Thr Lys

485 490 495

Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn Pro Pro Asp Gln Leu Val

500 505 510

Val Tyr Gln Gln Ala Val Val Gly Ala Met Leu Ser Glu Asn Phe Thr

515 520 525

Ser Tyr Gly Phe Ser Asn Val Val Glu Leu Pro Lys Phe Phe Tyr Ala

530 535 540

Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala Val Leu Thr Tyr Ser Ser

545 550 555 560

Phe Gly Val Cys Ala Asp Gly Ser Ile Ile Ala Val Gln Pro Ala Asn

565 570 575

Val Ser Tyr Asp Ser Val Ser Ala Ile Val Thr Ala Asn Leu Ser Ile

580 585 590

Pro Ser Asn Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr

595 600 605

Ser Thr Pro Ile Val Val Asp Cys Ser Thr Tyr Val Cys Asn Gly Asn

610 615 620

Val Arg Cys Val Glu Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr

625 630 635 640

Ile Glu Asp Ala Leu Arg Asn Ser Ala Arg Leu Glu Ser Ala Asp Val

645 650 655

Ser Glu Met Leu Thr Phe Asp Lys Lys Ala Phe Thr Leu Ala Asn Val

660 665 670

Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser Val Ile Pro Ser Leu Pro

675 680 685

Thr Ser Gly Ser Arg Val Ala Gly Arg Ser Ala Ile Glu Asp Ile Leu

690 695 700

Phe Ser Lys Leu Val Thr Ser Gly Leu Gly Thr Val Asp Ala Asp Tyr

705 710 715 720

Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln

725 730 735

Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg

740 745 750

Met Ala Met Tyr Thr Gly Ser Leu Ile Gly Gly Ile Ala Leu Gly Gly

755 760 765

Leu Thr Ser Ala Val Ser Ile Pro Phe Ser Leu Ala Ile Gln Ala Arg

770 775 780

Leu Asn Tyr Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys

785 790 795 800

Ile Leu Ala Ala Ser Phe Asn Lys Ala Met Thr Asn Ile Val Asp Ala

805 810 815

Phe Thr Gly Val Asn Asp Ala Ile Thr Gln Thr Ser Gln Ala Leu Gln

820 825 830

Thr Val Ala Thr Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln

835 840 845

Gly Asn Ser Leu Asn His Leu Thr Ser Gln Leu Arg Gln Asn Phe Gln

850 855 860

Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Pro Pro

865 870 875 880

Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala Ala

885 890 895

Leu Asn Val Phe Val Ser His Thr Leu Thr Lys Tyr Thr Glu Val Arg

900 905 910

Ala Ser Arg Gln Leu Ala Gln Gln Lys Val Asn Glu Cys Val Lys Ser

915 920 925

Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn Gly Thr His Ile Phe Ser

930 935 940

Ile Val Asn Ala Ala Pro Glu Gly Leu Val Phe Leu His Thr Val Leu

945 950 955 960

Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala Trp Ser Gly Leu Cys Val

965 970 975

Asp Gly Thr Asn Gly Tyr Val Leu Arg Gln Pro Asn Leu Ala Leu Tyr

980 985 990

Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser Arg Ile Met Phe Glu Pro

995 1000 1005

Arg Ile Pro Thr Met Ala Asp Phe Val Gln Ile Glu Asn Cys Asn Val

1010 1015 1020

Thr Phe Val Asn Ile Ser Arg Ser Glu Leu Gln Thr Ile Val Pro Glu

1025 1030 1035 1040

Tyr Ile Asp Val Asn Lys Thr Leu Gln Glu Leu Ser Tyr Lys Leu Pro

1045 1050 1055

Asn Tyr Thr Val Pro Asp Leu Val Val Glu Gln Tyr Asn Gln Thr Ile

1060 1065 1070

Leu Asn Leu Thr Ser Glu Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu

1075 1080 1085

Leu Asn Tyr Thr Val Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn

1090 1095 1100

Ser Thr Leu Val Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile

1105 1110 1115 1120

Lys Trp Pro Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe

1125 1130 1135

Val Val Ser Met Leu Leu Leu Cys Cys Cys Ser Thr Gly Cys Cys Gly

1140 1145 1150

Phe Phe Ser Cys Phe Ala Ser Ser Ile Arg Gly Cys Cys Glu Ser Thr

1155 1160 1165

Lys Leu Pro Tyr Tyr Asp Val Glu Lys Ile His Ile Gln

1170 1175 1180

<210> 154

<211> 1163

<212> PRT

<213> artificial sequence

<220>

<223> PDI-229E -H5iTMCT-AA

<400> 154

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Gln Thr Thr Asn Gly Leu Asn Thr

20 25 30

Ser Tyr Ser Val Cys Asn Gly Cys Val Gly Tyr Ser Glu Asn Val Phe

35 40 45

Ala Val Glu Ser Gly Gly Tyr Ile Pro Ser Asp Phe Ala Phe Asn Asn

50 55 60

Trp Phe Leu Leu Thr Asn Thr Ser Ser Val Val Asp Gly Val Val Arg

65 70 75 80

Ser Phe Gln Pro Leu Leu Leu Asn Cys Leu Trp Ser Val Ser Gly Leu

85 90 95

Arg Phe Thr Thr Gly Phe Val Tyr Phe Asn Gly Thr Gly Arg Gly Asp

100 105 110

Cys Lys Gly Phe Ser Ser Asp Val Leu Ser Asp Val Ile Arg Tyr Asn

115 120 125

Leu Asn Phe Glu Glu Asn Leu Arg Arg Gly Thr Ile Leu Phe Lys Thr

130 135 140

Ser Tyr Gly Val Val Val Phe Tyr Cys Thr Asn Asn Thr Leu Val Ser

145 150 155 160

Gly Asp Ala His Ile Pro Phe Gly Thr Val Leu Gly Asn Phe Tyr Cys

165 170 175

Phe Val Asn Thr Thr Ile Gly Asn Glu Thr Thr Ser Ala Phe Val Gly

180 185 190

Ala Leu Pro Lys Thr Val Arg Glu Phe Val Ile Ser Arg Thr Gly His

195 200 205

Phe Tyr Ile Asn Gly Tyr Arg Tyr Phe Thr Leu Gly Asn Val Glu Ala

210 215 220

Val Asn Phe Asn Val Thr Thr Ala Glu Thr Thr Asp Phe Cys Thr Val

225 230 235 240

Ala Leu Ala Ser Tyr Ala Asp Val Leu Val Asn Val Ser Gln Thr Ser

245 250 255

Ile Ala Asn Ile Ile Tyr Cys Asn Ser Val Ile Asn Arg Leu Arg Cys

260 265 270

Asp Gln Leu Ser Phe Asp Val Pro Asp Gly Phe Tyr Ser Thr Ser Pro

275 280 285

Ile Gln Ser Val Glu Leu Pro Val Ser Ile Val Ser Leu Pro Val Tyr

290 295 300

His Lys His Thr Phe Ile Val Leu Tyr Val Asp Phe Lys Pro Gln Ser

305 310 315 320

Gly Gly Gly Lys Cys Phe Asn Cys Tyr Pro Ala Gly Val Asn Ile Thr

325 330 335

Leu Ala Asn Phe Asn Glu Thr Lys Gly Pro Leu Cys Val Asp Thr Ser

340 345 350

His Phe Thr Thr Lys Tyr Val Ala Val Tyr Ala Asn Val Gly Arg Trp

355 360 365

Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro Phe Ser Phe Gly Lys Val

370 375 380

Asn Asn Phe Val Lys Phe Gly Ser Val Cys Phe Ser Leu Lys Asp Ile

385 390 395 400

Pro Gly Gly Cys Ala Met Pro Ile Val Ala Asn Trp Ala Tyr Ser Lys

405 410 415

Tyr Tyr Thr Ile Gly Ser Leu Tyr Val Ser Trp Ser Asp Gly Asp Gly

420 425 430

Ile Thr Gly Val Pro Gln Pro Val Glu Gly Val Ser Ser Phe Met Asn

435 440 445

Val Thr Leu Asp Lys Cys Thr Lys Tyr Asn Ile Tyr Asp Val Ser Gly

450 455 460

Val Gly Val Ile Arg Val Ser Asn Asp Thr Phe Leu Asn Gly Ile Thr

465 470 475 480

Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly Phe Lys Asp Val Thr Lys

485 490 495

Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn Pro Pro Asp Gln Leu Val

500 505 510

Val Tyr Gln Gln Ala Val Val Gly Ala Met Leu Ser Glu Asn Phe Thr

515 520 525

Ser Tyr Gly Phe Ser Asn Val Val Glu Leu Pro Lys Phe Phe Tyr Ala

530 535 540

Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala Val Leu Thr Tyr Ser Ser

545 550 555 560

Phe Gly Val Cys Ala Asp Gly Ser Ile Ile Ala Val Gln Pro Ala Asn

565 570 575

Val Ser Tyr Asp Ser Val Ser Ala Ile Val Thr Ala Asn Leu Ser Ile

580 585 590

Pro Ser Asn Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr

595 600 605

Ser Thr Pro Ile Val Val Asp Cys Ser Thr Tyr Val Cys Asn Gly Asn

610 615 620

Val Arg Cys Val Glu Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr

625 630 635 640

Ile Glu Asp Ala Leu Arg Asn Ser Ala Arg Leu Glu Ser Ala Asp Val

645 650 655

Ser Glu Met Leu Thr Phe Asp Lys Lys Ala Phe Thr Leu Ala Asn Val

660 665 670

Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser Val Ile Pro Ser Leu Pro

675 680 685

Thr Ser Gly Ser Arg Val Ala Gly Arg Ser Ala Ile Glu Asp Ile Leu

690 695 700

Phe Ser Lys Leu Val Thr Ser Gly Leu Gly Thr Val Asp Ala Asp Tyr

705 710 715 720

Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln

725 730 735

Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg

740 745 750

Met Ala Met Tyr Thr Gly Ser Leu Ile Gly Gly Ile Ala Leu Gly Gly

755 760 765

Leu Thr Ser Ala Val Ser Ile Pro Phe Ser Leu Ala Ile Gln Ala Arg

770 775 780

Leu Asn Tyr Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys

785 790 795 800

Ile Leu Ala Ala Ser Phe Asn Lys Ala Met Thr Asn Ile Val Asp Ala

805 810 815

Phe Thr Gly Val Asn Asp Ala Ile Thr Gln Thr Ser Gln Ala Leu Gln

820 825 830

Thr Val Ala Thr Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln

835 840 845

Gly Asn Ser Leu Asn His Leu Thr Ser Gln Leu Arg Gln Asn Phe Gln

850 855 860

Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Pro Pro

865 870 875 880

Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala Ala

885 890 895

Leu Asn Val Phe Val Ser His Thr Leu Thr Lys Tyr Thr Glu Val Arg

900 905 910

Ala Ser Arg Gln Leu Ala Gln Gln Lys Val Asn Glu Cys Val Lys Ser

915 920 925

Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn Gly Thr His Ile Phe Ser

930 935 940

Ile Val Asn Ala Ala Pro Glu Gly Leu Val Phe Leu His Thr Val Leu

945 950 955 960

Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala Trp Ser Gly Leu Cys Val

965 970 975

Asp Gly Thr Asn Gly Tyr Val Leu Arg Gln Pro Asn Leu Ala Leu Tyr

980 985 990

Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser Arg Ile Met Phe Glu Pro

995 1000 1005

Arg Ile Pro Thr Met Ala Asp Phe Val Gln Ile Glu Asn Cys Asn Val

1010 1015 1020

Thr Phe Val Asn Ile Ser Arg Ser Glu Leu Gln Thr Ile Val Pro Glu

1025 1030 1035 1040

Tyr Ile Asp Val Asn Lys Thr Leu Gln Glu Leu Ser Tyr Lys Leu Pro

1045 1050 1055

Asn Tyr Thr Val Pro Asp Leu Val Val Glu Gln Tyr Asn Gln Thr Ile

1060 1065 1070

Leu Asn Leu Thr Ser Glu Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu

1075 1080 1085

Leu Asn Tyr Thr Val Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn

1090 1095 1100

Ser Thr Leu Val Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile

1105 1110 1115 1120

Lys Trp Pro Trp Trp Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser

1125 1130 1135

Ser Leu Ala Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys

1140 1145 1150

Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys Ile

1155 1160

<210> 155

<211> 1159

<212> PRT

<213> artificial sequence

<220>

<223> PDI-229E -H5iCT-AA

<400> 155

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Gln Thr Thr Asn Gly Leu Asn Thr

20 25 30

Ser Tyr Ser Val Cys Asn Gly Cys Val Gly Tyr Ser Glu Asn Val Phe

35 40 45

Ala Val Glu Ser Gly Gly Tyr Ile Pro Ser Asp Phe Ala Phe Asn Asn

50 55 60

Trp Phe Leu Leu Thr Asn Thr Ser Ser Val Val Asp Gly Val Val Arg

65 70 75 80

Ser Phe Gln Pro Leu Leu Leu Asn Cys Leu Trp Ser Val Ser Gly Leu

85 90 95

Arg Phe Thr Thr Gly Phe Val Tyr Phe Asn Gly Thr Gly Arg Gly Asp

100 105 110

Cys Lys Gly Phe Ser Ser Asp Val Leu Ser Asp Val Ile Arg Tyr Asn

115 120 125

Leu Asn Phe Glu Glu Asn Leu Arg Arg Gly Thr Ile Leu Phe Lys Thr

130 135 140

Ser Tyr Gly Val Val Val Phe Tyr Cys Thr Asn Asn Thr Leu Val Ser

145 150 155 160

Gly Asp Ala His Ile Pro Phe Gly Thr Val Leu Gly Asn Phe Tyr Cys

165 170 175

Phe Val Asn Thr Thr Ile Gly Asn Glu Thr Thr Ser Ala Phe Val Gly

180 185 190

Ala Leu Pro Lys Thr Val Arg Glu Phe Val Ile Ser Arg Thr Gly His

195 200 205

Phe Tyr Ile Asn Gly Tyr Arg Tyr Phe Thr Leu Gly Asn Val Glu Ala

210 215 220

Val Asn Phe Asn Val Thr Thr Ala Glu Thr Thr Asp Phe Cys Thr Val

225 230 235 240

Ala Leu Ala Ser Tyr Ala Asp Val Leu Val Asn Val Ser Gln Thr Ser

245 250 255

Ile Ala Asn Ile Ile Tyr Cys Asn Ser Val Ile Asn Arg Leu Arg Cys

260 265 270

Asp Gln Leu Ser Phe Asp Val Pro Asp Gly Phe Tyr Ser Thr Ser Pro

275 280 285

Ile Gln Ser Val Glu Leu Pro Val Ser Ile Val Ser Leu Pro Val Tyr

290 295 300

His Lys His Thr Phe Ile Val Leu Tyr Val Asp Phe Lys Pro Gln Ser

305 310 315 320

Gly Gly Gly Lys Cys Phe Asn Cys Tyr Pro Ala Gly Val Asn Ile Thr

325 330 335

Leu Ala Asn Phe Asn Glu Thr Lys Gly Pro Leu Cys Val Asp Thr Ser

340 345 350

His Phe Thr Thr Lys Tyr Val Ala Val Tyr Ala Asn Val Gly Arg Trp

355 360 365

Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro Phe Ser Phe Gly Lys Val

370 375 380

Asn Asn Phe Val Lys Phe Gly Ser Val Cys Phe Ser Leu Lys Asp Ile

385 390 395 400

Pro Gly Gly Cys Ala Met Pro Ile Val Ala Asn Trp Ala Tyr Ser Lys

405 410 415

Tyr Tyr Thr Ile Gly Ser Leu Tyr Val Ser Trp Ser Asp Gly Asp Gly

420 425 430

Ile Thr Gly Val Pro Gln Pro Val Glu Gly Val Ser Ser Phe Met Asn

435 440 445

Val Thr Leu Asp Lys Cys Thr Lys Tyr Asn Ile Tyr Asp Val Ser Gly

450 455 460

Val Gly Val Ile Arg Val Ser Asn Asp Thr Phe Leu Asn Gly Ile Thr

465 470 475 480

Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly Phe Lys Asp Val Thr Lys

485 490 495

Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn Pro Pro Asp Gln Leu Val

500 505 510

Val Tyr Gln Gln Ala Val Val Gly Ala Met Leu Ser Glu Asn Phe Thr

515 520 525

Ser Tyr Gly Phe Ser Asn Val Val Glu Leu Pro Lys Phe Phe Tyr Ala

530 535 540

Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala Val Leu Thr Tyr Ser Ser

545 550 555 560

Phe Gly Val Cys Ala Asp Gly Ser Ile Ile Ala Val Gln Pro Ala Asn

565 570 575

Val Ser Tyr Asp Ser Val Ser Ala Ile Val Thr Ala Asn Leu Ser Ile

580 585 590

Pro Ser Asn Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr

595 600 605

Ser Thr Pro Ile Val Val Asp Cys Ser Thr Tyr Val Cys Asn Gly Asn

610 615 620

Val Arg Cys Val Glu Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr

625 630 635 640

Ile Glu Asp Ala Leu Arg Asn Ser Ala Arg Leu Glu Ser Ala Asp Val

645 650 655

Ser Glu Met Leu Thr Phe Asp Lys Lys Ala Phe Thr Leu Ala Asn Val

660 665 670

Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser Val Ile Pro Ser Leu Pro

675 680 685

Thr Ser Gly Ser Arg Val Ala Gly Arg Ser Ala Ile Glu Asp Ile Leu

690 695 700

Phe Ser Lys Leu Val Thr Ser Gly Leu Gly Thr Val Asp Ala Asp Tyr

705 710 715 720

Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln

725 730 735

Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg

740 745 750

Met Ala Met Tyr Thr Gly Ser Leu Ile Gly Gly Ile Ala Leu Gly Gly

755 760 765

Leu Thr Ser Ala Val Ser Ile Pro Phe Ser Leu Ala Ile Gln Ala Arg

770 775 780

Leu Asn Tyr Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys

785 790 795 800

Ile Leu Ala Ala Ser Phe Asn Lys Ala Met Thr Asn Ile Val Asp Ala

805 810 815

Phe Thr Gly Val Asn Asp Ala Ile Thr Gln Thr Ser Gln Ala Leu Gln

820 825 830

Thr Val Ala Thr Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln

835 840 845

Gly Asn Ser Leu Asn His Leu Thr Ser Gln Leu Arg Gln Asn Phe Gln

850 855 860

Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Pro Pro

865 870 875 880

Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala Ala

885 890 895

Leu Asn Val Phe Val Ser His Thr Leu Thr Lys Tyr Thr Glu Val Arg

900 905 910

Ala Ser Arg Gln Leu Ala Gln Gln Lys Val Asn Glu Cys Val Lys Ser

915 920 925

Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn Gly Thr His Ile Phe Ser

930 935 940

Ile Val Asn Ala Ala Pro Glu Gly Leu Val Phe Leu His Thr Val Leu

945 950 955 960

Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala Trp Ser Gly Leu Cys Val

965 970 975

Asp Gly Thr Asn Gly Tyr Val Leu Arg Gln Pro Asn Leu Ala Leu Tyr

980 985 990

Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser Arg Ile Met Phe Glu Pro

995 1000 1005

Arg Ile Pro Thr Met Ala Asp Phe Val Gln Ile Glu Asn Cys Asn Val

1010 1015 1020

Thr Phe Val Asn Ile Ser Arg Ser Glu Leu Gln Thr Ile Val Pro Glu

1025 1030 1035 1040

Tyr Ile Asp Val Asn Lys Thr Leu Gln Glu Leu Ser Tyr Lys Leu Pro

1045 1050 1055

Asn Tyr Thr Val Pro Asp Leu Val Val Glu Gln Tyr Asn Gln Thr Ile

1060 1065 1070

Leu Asn Leu Thr Ser Glu Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu

1075 1080 1085

Leu Asn Tyr Thr Val Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn

1090 1095 1100

Ser Thr Leu Val Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile

1105 1110 1115 1120

Lys Trp Pro Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe

1125 1130 1135

Val Val Ser Met Leu Leu Leu Ser Leu Trp Met Cys Ser Asn Gly Ser

1140 1145 1150

Leu Gln Cys Arg Ile Cys Ile

1155

<210> 156

<211> 1156

<212> PRT

<213> artificial sequence

<220>

<223> PDI-229E -H5iCT(V4)-AA

<400> 156

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Gln Thr Thr Asn Gly Leu Asn Thr

20 25 30

Ser Tyr Ser Val Cys Asn Gly Cys Val Gly Tyr Ser Glu Asn Val Phe

35 40 45

Ala Val Glu Ser Gly Gly Tyr Ile Pro Ser Asp Phe Ala Phe Asn Asn

50 55 60

Trp Phe Leu Leu Thr Asn Thr Ser Ser Val Val Asp Gly Val Val Arg

65 70 75 80

Ser Phe Gln Pro Leu Leu Leu Asn Cys Leu Trp Ser Val Ser Gly Leu

85 90 95

Arg Phe Thr Thr Gly Phe Val Tyr Phe Asn Gly Thr Gly Arg Gly Asp

100 105 110

Cys Lys Gly Phe Ser Ser Asp Val Leu Ser Asp Val Ile Arg Tyr Asn

115 120 125

Leu Asn Phe Glu Glu Asn Leu Arg Arg Gly Thr Ile Leu Phe Lys Thr

130 135 140

Ser Tyr Gly Val Val Val Phe Tyr Cys Thr Asn Asn Thr Leu Val Ser

145 150 155 160

Gly Asp Ala His Ile Pro Phe Gly Thr Val Leu Gly Asn Phe Tyr Cys

165 170 175

Phe Val Asn Thr Thr Ile Gly Asn Glu Thr Thr Ser Ala Phe Val Gly

180 185 190

Ala Leu Pro Lys Thr Val Arg Glu Phe Val Ile Ser Arg Thr Gly His

195 200 205

Phe Tyr Ile Asn Gly Tyr Arg Tyr Phe Thr Leu Gly Asn Val Glu Ala

210 215 220

Val Asn Phe Asn Val Thr Thr Ala Glu Thr Thr Asp Phe Cys Thr Val

225 230 235 240

Ala Leu Ala Ser Tyr Ala Asp Val Leu Val Asn Val Ser Gln Thr Ser

245 250 255

Ile Ala Asn Ile Ile Tyr Cys Asn Ser Val Ile Asn Arg Leu Arg Cys

260 265 270

Asp Gln Leu Ser Phe Asp Val Pro Asp Gly Phe Tyr Ser Thr Ser Pro

275 280 285

Ile Gln Ser Val Glu Leu Pro Val Ser Ile Val Ser Leu Pro Val Tyr

290 295 300

His Lys His Thr Phe Ile Val Leu Tyr Val Asp Phe Lys Pro Gln Ser

305 310 315 320

Gly Gly Gly Lys Cys Phe Asn Cys Tyr Pro Ala Gly Val Asn Ile Thr

325 330 335

Leu Ala Asn Phe Asn Glu Thr Lys Gly Pro Leu Cys Val Asp Thr Ser

340 345 350

His Phe Thr Thr Lys Tyr Val Ala Val Tyr Ala Asn Val Gly Arg Trp

355 360 365

Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro Phe Ser Phe Gly Lys Val

370 375 380

Asn Asn Phe Val Lys Phe Gly Ser Val Cys Phe Ser Leu Lys Asp Ile

385 390 395 400

Pro Gly Gly Cys Ala Met Pro Ile Val Ala Asn Trp Ala Tyr Ser Lys

405 410 415

Tyr Tyr Thr Ile Gly Ser Leu Tyr Val Ser Trp Ser Asp Gly Asp Gly

420 425 430

Ile Thr Gly Val Pro Gln Pro Val Glu Gly Val Ser Ser Phe Met Asn

435 440 445

Val Thr Leu Asp Lys Cys Thr Lys Tyr Asn Ile Tyr Asp Val Ser Gly

450 455 460

Val Gly Val Ile Arg Val Ser Asn Asp Thr Phe Leu Asn Gly Ile Thr

465 470 475 480

Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly Phe Lys Asp Val Thr Lys

485 490 495

Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn Pro Pro Asp Gln Leu Val

500 505 510

Val Tyr Gln Gln Ala Val Val Gly Ala Met Leu Ser Glu Asn Phe Thr

515 520 525

Ser Tyr Gly Phe Ser Asn Val Val Glu Leu Pro Lys Phe Phe Tyr Ala

530 535 540

Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala Val Leu Thr Tyr Ser Ser

545 550 555 560

Phe Gly Val Cys Ala Asp Gly Ser Ile Ile Ala Val Gln Pro Ala Asn

565 570 575

Val Ser Tyr Asp Ser Val Ser Ala Ile Val Thr Ala Asn Leu Ser Ile

580 585 590

Pro Ser Asn Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr

595 600 605

Ser Thr Pro Ile Val Val Asp Cys Ser Thr Tyr Val Cys Asn Gly Asn

610 615 620

Val Arg Cys Val Glu Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr

625 630 635 640

Ile Glu Asp Ala Leu Arg Asn Ser Ala Arg Leu Glu Ser Ala Asp Val

645 650 655

Ser Glu Met Leu Thr Phe Asp Lys Lys Ala Phe Thr Leu Ala Asn Val

660 665 670

Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser Val Ile Pro Ser Leu Pro

675 680 685

Thr Ser Gly Ser Arg Val Ala Gly Arg Ser Ala Ile Glu Asp Ile Leu

690 695 700

Phe Ser Lys Leu Val Thr Ser Gly Leu Gly Thr Val Asp Ala Asp Tyr

705 710 715 720

Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln

725 730 735

Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg

740 745 750

Met Ala Met Tyr Thr Gly Ser Leu Ile Gly Gly Ile Ala Leu Gly Gly

755 760 765

Leu Thr Ser Ala Val Ser Ile Pro Phe Ser Leu Ala Ile Gln Ala Arg

770 775 780

Leu Asn Tyr Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys

785 790 795 800

Ile Leu Ala Ala Ser Phe Asn Lys Ala Met Thr Asn Ile Val Asp Ala

805 810 815

Phe Thr Gly Val Asn Asp Ala Ile Thr Gln Thr Ser Gln Ala Leu Gln

820 825 830

Thr Val Ala Thr Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln

835 840 845

Gly Asn Ser Leu Asn His Leu Thr Ser Gln Leu Arg Gln Asn Phe Gln

850 855 860

Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Pro Pro

865 870 875 880

Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala Ala

885 890 895

Leu Asn Val Phe Val Ser His Thr Leu Thr Lys Tyr Thr Glu Val Arg

900 905 910

Ala Ser Arg Gln Leu Ala Gln Gln Lys Val Asn Glu Cys Val Lys Ser

915 920 925

Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn Gly Thr His Ile Phe Ser

930 935 940

Ile Val Asn Ala Ala Pro Glu Gly Leu Val Phe Leu His Thr Val Leu

945 950 955 960

Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala Trp Ser Gly Leu Cys Val

965 970 975

Asp Gly Thr Asn Gly Tyr Val Leu Arg Gln Pro Asn Leu Ala Leu Tyr

980 985 990

Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser Arg Ile Met Phe Glu Pro

995 1000 1005

Arg Ile Pro Thr Met Ala Asp Phe Val Gln Ile Glu Asn Cys Asn Val

1010 1015 1020

Thr Phe Val Asn Ile Ser Arg Ser Glu Leu Gln Thr Ile Val Pro Glu

1025 1030 1035 1040

Tyr Ile Asp Val Asn Lys Thr Leu Gln Glu Leu Ser Tyr Lys Leu Pro

1045 1050 1055

Asn Tyr Thr Val Pro Asp Leu Val Val Glu Gln Tyr Asn Gln Thr Ile

1060 1065 1070

Leu Asn Leu Thr Ser Glu Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu

1075 1080 1085

Leu Asn Tyr Thr Val Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn

1090 1095 1100

Ser Thr Leu Val Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile

1105 1110 1115 1120

Lys Trp Pro Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe

1125 1130 1135

Val Val Ser Met Leu Leu Leu Cys Cys Ser Asn Gly Ser Leu Gln Cys

1140 1145 1150

Arg Ile Cys Ile

1155

<210> 157

<211> 1159

<212> PRT

<213> artificial sequence

<220>

<223> PDI-229E-H1cCT-AA

<400> 157

Met Ala Lys Asn Val Ala Ile Phe Gly Leu Leu Phe Ser Leu Leu Val

1 5 10 15

Leu Val Pro Ser Gln Ile Phe Ala Gln Thr Thr Asn Gly Leu Asn Thr

20 25 30

Ser Tyr Ser Val Cys Asn Gly Cys Val Gly Tyr Ser Glu Asn Val Phe

35 40 45

Ala Val Glu Ser Gly Gly Tyr Ile Pro Ser Asp Phe Ala Phe Asn Asn

50 55 60

Trp Phe Leu Leu Thr Asn Thr Ser Ser Val Val Asp Gly Val Val Arg

65 70 75 80

Ser Phe Gln Pro Leu Leu Leu Asn Cys Leu Trp Ser Val Ser Gly Leu

85 90 95

Arg Phe Thr Thr Gly Phe Val Tyr Phe Asn Gly Thr Gly Arg Gly Asp

100 105 110

Cys Lys Gly Phe Ser Ser Asp Val Leu Ser Asp Val Ile Arg Tyr Asn

115 120 125

Leu Asn Phe Glu Glu Asn Leu Arg Arg Gly Thr Ile Leu Phe Lys Thr

130 135 140

Ser Tyr Gly Val Val Val Phe Tyr Cys Thr Asn Asn Thr Leu Val Ser

145 150 155 160

Gly Asp Ala His Ile Pro Phe Gly Thr Val Leu Gly Asn Phe Tyr Cys

165 170 175

Phe Val Asn Thr Thr Ile Gly Asn Glu Thr Thr Ser Ala Phe Val Gly

180 185 190

Ala Leu Pro Lys Thr Val Arg Glu Phe Val Ile Ser Arg Thr Gly His

195 200 205

Phe Tyr Ile Asn Gly Tyr Arg Tyr Phe Thr Leu Gly Asn Val Glu Ala

210 215 220

Val Asn Phe Asn Val Thr Thr Ala Glu Thr Thr Asp Phe Cys Thr Val

225 230 235 240

Ala Leu Ala Ser Tyr Ala Asp Val Leu Val Asn Val Ser Gln Thr Ser

245 250 255

Ile Ala Asn Ile Ile Tyr Cys Asn Ser Val Ile Asn Arg Leu Arg Cys

260 265 270

Asp Gln Leu Ser Phe Asp Val Pro Asp Gly Phe Tyr Ser Thr Ser Pro

275 280 285

Ile Gln Ser Val Glu Leu Pro Val Ser Ile Val Ser Leu Pro Val Tyr

290 295 300

His Lys His Thr Phe Ile Val Leu Tyr Val Asp Phe Lys Pro Gln Ser

305 310 315 320

Gly Gly Gly Lys Cys Phe Asn Cys Tyr Pro Ala Gly Val Asn Ile Thr

325 330 335

Leu Ala Asn Phe Asn Glu Thr Lys Gly Pro Leu Cys Val Asp Thr Ser

340 345 350

His Phe Thr Thr Lys Tyr Val Ala Val Tyr Ala Asn Val Gly Arg Trp

355 360 365

Ser Ala Ser Ile Asn Thr Gly Asn Cys Pro Phe Ser Phe Gly Lys Val

370 375 380

Asn Asn Phe Val Lys Phe Gly Ser Val Cys Phe Ser Leu Lys Asp Ile

385 390 395 400

Pro Gly Gly Cys Ala Met Pro Ile Val Ala Asn Trp Ala Tyr Ser Lys

405 410 415

Tyr Tyr Thr Ile Gly Ser Leu Tyr Val Ser Trp Ser Asp Gly Asp Gly

420 425 430

Ile Thr Gly Val Pro Gln Pro Val Glu Gly Val Ser Ser Phe Met Asn

435 440 445

Val Thr Leu Asp Lys Cys Thr Lys Tyr Asn Ile Tyr Asp Val Ser Gly

450 455 460

Val Gly Val Ile Arg Val Ser Asn Asp Thr Phe Leu Asn Gly Ile Thr

465 470 475 480

Tyr Thr Ser Thr Ser Gly Asn Leu Leu Gly Phe Lys Asp Val Thr Lys

485 490 495

Gly Thr Ile Tyr Ser Ile Thr Pro Cys Asn Pro Pro Asp Gln Leu Val

500 505 510

Val Tyr Gln Gln Ala Val Val Gly Ala Met Leu Ser Glu Asn Phe Thr

515 520 525

Ser Tyr Gly Phe Ser Asn Val Val Glu Leu Pro Lys Phe Phe Tyr Ala

530 535 540

Ser Asn Gly Thr Tyr Asn Cys Thr Asp Ala Val Leu Thr Tyr Ser Ser

545 550 555 560

Phe Gly Val Cys Ala Asp Gly Ser Ile Ile Ala Val Gln Pro Ala Asn

565 570 575

Val Ser Tyr Asp Ser Val Ser Ala Ile Val Thr Ala Asn Leu Ser Ile

580 585 590

Pro Ser Asn Trp Thr Thr Ser Val Gln Val Glu Tyr Leu Gln Ile Thr

595 600 605

Ser Thr Pro Ile Val Val Asp Cys Ser Thr Tyr Val Cys Asn Gly Asn

610 615 620

Val Arg Cys Val Glu Leu Leu Lys Gln Tyr Thr Ser Ala Cys Lys Thr

625 630 635 640

Ile Glu Asp Ala Leu Arg Asn Ser Ala Arg Leu Glu Ser Ala Asp Val

645 650 655

Ser Glu Met Leu Thr Phe Asp Lys Lys Ala Phe Thr Leu Ala Asn Val

660 665 670

Ser Ser Phe Gly Asp Tyr Asn Leu Ser Ser Val Ile Pro Ser Leu Pro

675 680 685

Thr Ser Gly Ser Arg Val Ala Gly Arg Ser Ala Ile Glu Asp Ile Leu

690 695 700

Phe Ser Lys Leu Val Thr Ser Gly Leu Gly Thr Val Asp Ala Asp Tyr

705 710 715 720

Lys Lys Cys Thr Lys Gly Leu Ser Ile Ala Asp Leu Ala Cys Ala Gln

725 730 735

Tyr Tyr Asn Gly Ile Met Val Leu Pro Gly Val Ala Asp Ala Glu Arg

740 745 750

Met Ala Met Tyr Thr Gly Ser Leu Ile Gly Gly Ile Ala Leu Gly Gly

755 760 765

Leu Thr Ser Ala Val Ser Ile Pro Phe Ser Leu Ala Ile Gln Ala Arg

770 775 780

Leu Asn Tyr Val Ala Leu Gln Thr Asp Val Leu Gln Glu Asn Gln Lys

785 790 795 800

Ile Leu Ala Ala Ser Phe Asn Lys Ala Met Thr Asn Ile Val Asp Ala

805 810 815

Phe Thr Gly Val Asn Asp Ala Ile Thr Gln Thr Ser Gln Ala Leu Gln

820 825 830

Thr Val Ala Thr Ala Leu Asn Lys Ile Gln Asp Val Val Asn Gln Gln

835 840 845

Gly Asn Ser Leu Asn His Leu Thr Ser Gln Leu Arg Gln Asn Phe Gln

850 855 860

Ala Ile Ser Ser Ser Ile Gln Ala Ile Tyr Asp Arg Leu Asp Pro Pro

865 870 875 880

Gln Ala Asp Gln Gln Val Asp Arg Leu Ile Thr Gly Arg Leu Ala Ala

885 890 895

Leu Asn Val Phe Val Ser His Thr Leu Thr Lys Tyr Thr Glu Val Arg

900 905 910

Ala Ser Arg Gln Leu Ala Gln Gln Lys Val Asn Glu Cys Val Lys Ser

915 920 925

Gln Ser Lys Arg Tyr Gly Phe Cys Gly Asn Gly Thr His Ile Phe Ser

930 935 940

Ile Val Asn Ala Ala Pro Glu Gly Leu Val Phe Leu His Thr Val Leu

945 950 955 960

Leu Pro Thr Gln Tyr Lys Asp Val Glu Ala Trp Ser Gly Leu Cys Val

965 970 975

Asp Gly Thr Asn Gly Tyr Val Leu Arg Gln Pro Asn Leu Ala Leu Tyr

980 985 990

Lys Glu Gly Asn Tyr Tyr Arg Ile Thr Ser Arg Ile Met Phe Glu Pro

995 1000 1005

Arg Ile Pro Thr Met Ala Asp Phe Val Gln Ile Glu Asn Cys Asn Val

1010 1015 1020

Thr Phe Val Asn Ile Ser Arg Ser Glu Leu Gln Thr Ile Val Pro Glu

1025 1030 1035 1040

Tyr Ile Asp Val Asn Lys Thr Leu Gln Glu Leu Ser Tyr Lys Leu Pro

1045 1050 1055

Asn Tyr Thr Val Pro Asp Leu Val Val Glu Gln Tyr Asn Gln Thr Ile

1060 1065 1070

Leu Asn Leu Thr Ser Glu Ile Ser Thr Leu Glu Asn Lys Ser Ala Glu

1075 1080 1085

Leu Asn Tyr Thr Val Gln Lys Leu Gln Thr Leu Ile Asp Asn Ile Asn

1090 1095 1100

Ser Thr Leu Val Asp Leu Lys Trp Leu Asn Arg Val Glu Thr Tyr Ile

1105 1110 1115 1120

Lys Trp Pro Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe

1125 1130 1135

Val Val Ser Met Leu Leu Leu Ser Phe Trp Met Cys Ser Asn Gly Ser

1140 1145 1150

Leu Gln Cys Arg Ile Cys Ile

1155

<210> 158

<211> 1360

<212> PRT

<213> OC 43-coronavirus

<400> 158

Met Phe Leu Ile Leu Leu Ile Ser Leu Pro Thr Ala Phe Ala Val Ile

1 5 10 15

Gly Asp Leu Asn Cys Thr Leu Asp Pro Arg Leu Lys Gly Ser Phe Asn

20 25 30

Asn Arg Asp Thr Gly Pro Pro Ser Ile Ser Ile Asp Thr Val Asp Val

35 40 45

Thr Asn Gly Leu Gly Thr Tyr Tyr Val Leu Asp Arg Val Tyr Leu Asn

50 55 60

Thr Thr Leu Phe Leu Asn Gly Tyr Tyr Pro Thr Ser Gly Ser Thr Tyr

65 70 75 80

Arg Asn Met Ala Leu Lys Gly Thr Asp Leu Leu Ser Thr Leu Trp Phe

85 90 95

Lys Pro Pro Phe Leu Ser Asp Phe Ile Asn Gly Ile Phe Ala Lys Val

100 105 110

Lys Asn Thr Lys Val Phe Lys Asp Gly Val Met Tyr Ser Glu Phe Pro

115 120 125

Ala Ile Thr Ile Gly Ser Thr Phe Val Asn Thr Ser Tyr Ser Val Val

130 135 140

Val Gln Pro Arg Thr Ile Asn Ser Thr Gln Asp Gly Val Asn Lys Leu

145 150 155 160

Gln Gly Leu Leu Glu Val Ser Val Cys Gln Tyr Asn Met Cys Glu Tyr

165 170 175

Pro His Thr Ile Cys His Pro Asn Leu Gly Asn His Phe Lys Glu Leu

180 185 190

Trp His Tyr Asp Thr Gly Val Val Ser Cys Leu Tyr Lys Arg Asn Phe

195 200 205

Thr Tyr Asp Val Asn Ala Thr Tyr Leu Tyr Phe His Phe Tyr Gln Glu

210 215 220

Gly Gly Thr Phe Tyr Ala Tyr Phe Thr Asp Thr Gly Phe Val Thr Lys

225 230 235 240

Phe Leu Phe Asn Val Tyr Leu Gly Met Ala Leu Ser His Tyr Tyr Val

245 250 255

Met Pro Leu Thr Cys Ile Arg Arg Pro Lys Asp Gly Phe Ser Leu Glu

260 265 270

Tyr Trp Val Thr Pro Leu Thr Pro Arg Gln Tyr Leu Leu Ala Phe Asn

275 280 285

Gln Asp Gly Ile Ile Phe Asn Ala Val Asp Cys Met Ser Asp Phe Met

290 295 300

Ser Glu Ile Lys Cys Lys Thr Gln Ser Ile Ala Pro Pro Thr Gly Val

305 310 315 320

Tyr Glu Leu Asn Gly Tyr Thr Val Gln Pro Val Ala Asp Val Tyr Arg

325 330 335

Arg Lys Pro Asp Leu Pro Asn Cys Asn Ile Glu Ala Trp Leu Asn Asp

340 345 350

Lys Ser Val Pro Ser Pro Leu Asn Trp Glu Arg Lys Thr Phe Ser Asn

355 360 365

Cys Asn Phe Asn Met Ser Ser Leu Met Ser Phe Ile Gln Ala Asp Ser

370 375 380

Phe Thr Cys Asn Asn Ile Asp Ala Ala Lys Ile Tyr Gly Met Cys Phe

385 390 395 400

Ser Ser Ile Thr Ile Asp Lys Phe Ala Ile Pro Asn Arg Arg Lys Val

405 410 415

Asp Leu Gln Leu Gly Asn Leu Gly Tyr Leu Gln Ser Ser Asn Tyr Arg

420 425 430

Ile Asp Thr Thr Ala Thr Ser Cys Gln Leu Tyr Tyr Asn Leu Pro Ala

435 440 445

Ala Asn Val Ser Val Ser Arg Phe Asn Pro Ser Thr Trp Asn Lys Arg

450 455 460

Phe Gly Phe Ile Glu Asp Ser Val Phe Val Pro Gln Pro Thr Gly Val

465 470 475 480

Phe Thr Asn His Ser Val Val Tyr Ala Gln His Cys Phe Lys Ala Pro

485 490 495

Lys Asn Phe Cys Pro Cys Ser Ser Cys Ser Cys Pro Gly Lys Asn Asn

500 505 510

Gly Ile Gly Thr Cys Pro Ala Gly Thr Asn Ser Leu Thr Cys Asp Asn

515 520 525

Leu Cys Thr Leu Asp Pro Ile Thr Leu Lys Ala Pro Asp Thr Tyr Lys

530 535 540

Cys Pro Gln Ser Lys Ser Leu Val Gly Ile Gly Glu His Cys Ser Gly

545 550 555 560

Leu Ala Val Lys Ser Asp Tyr Cys Gly Asn Asn Ser Cys Thr Cys Gln

565 570 575

Pro Gln Ala Phe Leu Gly Trp Ser Ala Asp Ser Cys Leu Gln Gly Asp

580 585 590

Lys Cys Asn Ile Phe Ala Asn Phe Ile Leu His Asp Val Asn Asn Gly

595 600 605

Leu Thr Cys Ser Thr Asp Leu Gln Lys Ala Asn Thr Glu Ile Glu Leu

610 615 620

Gly Val Cys Val Asn Tyr Asp Leu Tyr Gly Ile Ser Gly Gln Gly Ile

625 630 635 640

Phe Val Glu Val Asn Ala Thr Tyr Tyr Asn Ser Trp Gln Asn Leu Leu

645 650 655

Tyr Asp Ser Asn Gly Asn Leu Tyr Gly Phe Arg Asp Tyr Ile Thr Asn

660 665 670

Arg Thr Phe Met Ile His Ser Cys Tyr Ser Gly Arg Val Ser Ala Ala

675 680 685

Tyr His Ala Asn Ser Ser Glu Pro Ala Leu Leu Phe Arg Asn Ile Lys

690 695 700

Cys Asn Tyr Val Phe Asn Asn Ser Leu Thr Arg Gln Leu Gln Pro Ile

705 710 715 720

Asn Tyr Ser Phe Asp Ser Tyr Leu Gly Cys Val Val Asn Ala Tyr Asn

725 730 735

Ser Thr Ala Ile Ser Val Gln Thr Cys Asp Leu Thr Val Gly Ser Gly

740 745 750

Tyr Cys Val Asp Tyr Ser Lys Asn Arg Arg Ser Arg Arg Ala Ile Thr

755 760 765

Thr Gly Tyr Arg Phe Thr Asn Phe Glu Pro Phe Thr Val Asn Ser Val

770 775 780

Asn Asp Ser Leu Glu Pro Val Gly Gly Leu Tyr Glu Ile Gln Ile Pro

785 790 795 800

Ser Glu Phe Thr Ile Gly Asn Met Glu Glu Phe Ile Gln Thr Ser Ser

805 810 815

Pro Lys Val Thr Ile Asp Cys Ala Ala Phe Val Cys Gly Asp Tyr Ala

820 825 830

Ala Cys Lys Leu Gln Leu Val Glu Tyr Gly Ser Phe Cys Asp Asn Ile

835 840 845

Asn Ala Ile Leu Thr Glu Val Asn Glu Leu Leu Asp Thr Thr Gln Leu

850 855 860

Gln Val Ala Asn Ser Leu Met Asn Gly Val Thr Leu Ser Thr Lys Leu

865 870 875 880

Lys Asp Gly Val Asn Phe Asn Val Asp Asp Ile Asn Phe Ser Pro Val

885 890 895

Leu Gly Cys Leu Gly Ser Glu Cys Ser Lys Ala Ser Ser Arg Ser Ala

900 905 910

Ile Glu Asp Leu Leu Phe Asp Lys Val Lys Leu Ser Asp Val Gly Phe

915 920 925

Val Glu Ala Tyr Asn Asn Cys Thr Gly Gly Ala Glu Ile Arg Asp Leu

930 935 940

Ile Cys Val Gln Ser Tyr Lys Gly Ile Lys Val Leu Pro Pro Leu Leu

945 950 955 960

Ser Glu Asn Gln Ile Ser Gly Tyr Thr Leu Ala Ala Thr Ser Ala Ser

965 970 975

Leu Phe Pro Pro Trp Thr Ala Ala Ala Gly Val Pro Phe Tyr Leu Asn

980 985 990

Val Gln Tyr Arg Ile Asn Gly Leu Gly Val Thr Met Asp Val Leu Ser

995 1000 1005

Gln Asn Gln Lys Leu Ile Ala Asn Ala Phe Asn Asn Ala Leu His Ala

1010 1015 1020

Ile Gln Gln Gly Phe Asp Ala Thr Asn Ser Ala Leu Val Lys Ile Gln

1025 1030 1035 1040

Ala Val Val Asn Ala Asn Ala Glu Ala Leu Asn Asn Leu Leu Gln Gln

1045 1050 1055

Leu Ser Asn Arg Phe Gly Ala Ile Ser Ala Ser Leu Gln Glu Ile Leu

1060 1065 1070

Ser Arg Leu Asp Ala Leu Glu Ala Glu Ala Gln Ile Asp Arg Leu Ile

1075 1080 1085

Asn Gly Arg Leu Thr Ala Leu Asn Ala Tyr Val Ser Gln Gln Leu Ser

1090 1095 1100

Asp Ser Thr Leu Val Lys Phe Ser Ala Ala Gln Ala Met Glu Lys Val

1105 1110 1115 1120

Asn Glu Cys Val Lys Ser Gln Ser Ser Arg Ile Asn Phe Cys Gly Asn

1125 1130 1135

Gly Asn His Ile Ile Ser Leu Val Gln Asn Ala Pro Tyr Gly Leu Tyr

1140 1145 1150

Phe Ile His Phe Asn Tyr Val Pro Thr Lys Tyr Val Thr Ala Lys Val

1155 1160 1165

Ser Pro Gly Leu Cys Ile Ala Gly Asn Arg Gly Ile Ala Pro Lys Ser

1170 1175 1180

Gly Tyr Phe Val Asn Val Asn Asn Thr Trp Met Tyr Thr Gly Ser Gly

1185 1190 1195 1200

Tyr Tyr Tyr Pro Glu Pro Ile Thr Glu Asn Asn Val Val Val Met Ser

1205 1210 1215

Thr Cys Ala Val Asn Tyr Thr Lys Ala Pro Tyr Val Met Leu Asn Thr

1220 1225 1230

Ser Ile Pro Asn Leu Pro Asp Phe Lys Glu Glu Leu Asp Gln Trp Phe

1235 1240 1245

Lys Asn Gln Thr Ser Val Ala Pro Asp Leu Ser Leu Asp Tyr Ile Asn

1250 1255 1260

Val Thr Phe Leu Asp Leu Gln Val Glu Met Asn Arg Leu Gln Glu Ala

1265 1270 1275 1280

Ile Lys Val Leu Asn His Ser Tyr Ile Asn Leu Lys Asp Ile Gly Thr

1285 1290 1295

Tyr Glu Tyr Tyr Val Lys Trp Pro Trp Tyr Val Trp Leu Leu Ile Cys

1300 1305 1310

Leu Ala Gly Val Ala Met Leu Val Leu Leu Phe Phe Ile Cys Cys Cys

1315 1320 1325

Thr Gly Cys Gly Thr Ser Cys Phe Lys Lys Cys Gly Gly Cys Cys Asp

1330 1335 1340

Asp Tyr Thr Gly Tyr Gln Glu Leu Val Ile Lys Thr Ser His Asp Asp

1345 1350 1355 1360

<210> 159

<211> 1173

<212> PRT

<213> 229E coronavirus

<400> 159

Met Phe Val Leu Leu Val Ala Tyr Ala Leu Leu His Ile Ala Gly Cys

1 5 10 15

Gln Thr Thr Asn Gly Leu Asn Thr Ser Tyr Ser Val Cys Asn Gly Cys

20 25 30

Val Gly Tyr Ser Glu Asn Val Phe Ala Val Glu Ser Gly Gly Tyr Ile

35 40 45

Pro Ser Asp Phe Ala Phe Asn Asn Trp Phe Leu Leu Thr Asn Thr Ser

50 55 60

Ser Val Val Asp Gly Val Val Arg Ser Phe Gln Pro Leu Leu Leu Asn

65 70 75 80

Cys Leu Trp Ser Val Ser Gly Leu Arg Phe Thr Thr Gly Phe Val Tyr

85 90 95

Phe Asn Gly Thr Gly Arg Gly Asp Cys Lys Gly Phe Ser Ser Asp Val

100 105 110

Leu Ser Asp Val Ile Arg Tyr Asn Leu Asn Phe Glu Glu Asn Leu Arg

115 120 125

Arg Gly Thr Ile Leu Phe Lys Thr Ser Tyr Gly Val Val Val Phe Tyr

130 135 140

Cys Thr Asn Asn Thr Leu Val Ser Gly Asp Ala His Ile Pro Phe Gly

145 150 155 160

Thr Val Leu Gly Asn Phe Tyr Cys Phe Val Asn Thr Thr Ile Gly Asn

165 170 175

Glu Thr Thr Ser Ala Phe Val Gly Ala Leu Pro Lys Thr Val Arg Glu

180 185 190

Phe Val Ile Ser Arg Thr Gly His Phe Tyr Ile Asn Gly Tyr Arg Tyr

195 200 205

Phe Thr Leu Gly Asn Val Glu Ala Val Asn Phe Asn Val Thr Thr Ala

210 215 220

Glu Thr Thr Asp Phe Cys Thr Val Ala Leu Ala Ser Tyr Ala Asp Val

225 230 235 240

Leu Val Asn Val Ser Gln Thr Ser Ile Ala Asn Ile Ile Tyr Cys Asn

245 250 255

Ser Val Ile Asn Arg Leu Arg Cys Asp Gln Leu Ser Phe Asp Val Pro

260 265 270

Asp Gly Phe Tyr Ser Thr Ser Pro Ile Gln Ser Val Glu Leu Pro Val

275 280 285

Ser Ile Val Ser Leu Pro Val Tyr His Lys His Thr Phe Ile Val Leu

290 295 300

Tyr Val Asp Phe Lys Pro Gln Ser Gly Gly Gly Lys Cys Phe Asn Cys

305 310 315 320

Tyr Pro Ala Gly Val Asn Ile Thr Leu Ala Asn Phe Asn Glu Thr Lys

325 330 335

Gly Pro Leu Cys Val Asp Thr Ser His Phe Thr Thr Lys Tyr Val Ala

340 345 350

Val Tyr Ala Asn Val Gly Arg Trp Ser Ala Ser Ile Asn Thr Gly Asn

355 360 365

Cys Pro Phe Ser Phe Gly Lys Val Asn Asn Phe Val Lys Phe Gly Ser

370 375 380

Val Cys Phe Ser Leu Lys Asp Ile Pro Gly Gly Cys Ala Met Pro Ile

385 390 395 400

Val Ala Asn Trp Ala Tyr Ser Lys Tyr Tyr Thr Ile Gly Ser Leu Tyr

405 410 415

Val Ser Trp Ser Asp Gly Asp Gly Ile Thr Gly Val Pro Gln Pro Val

420 425 430

Glu Gly Val Ser Ser Phe Met Asn Val Thr Leu Asp Lys Cys Thr Lys

435 440 445

Tyr Asn Ile Tyr Asp Val Ser Gly Val Gly Val Ile Arg Val Ser Asn

450 455 460

Asp Thr Phe Leu Asn Gly Ile Thr Tyr Thr Ser Thr Ser Gly Asn Leu

465 470 475 480

Leu Gly Phe Lys Asp Val Thr Lys Gly Thr Ile Tyr Ser Ile Thr Pro

485 490 495

Cys Asn Pro Pro Asp Gln Leu Val Val Tyr Gln Gln Ala Val Val Gly

500 505 510

Ala Met Leu Ser Glu Asn Phe Thr Ser Tyr Gly Phe Ser Asn Val Val

515 520 525

Glu Leu Pro Lys Phe Phe Tyr Ala Ser Asn Gly Thr Tyr Asn Cys Thr

530 535 540

Asp Ala Val Leu Thr Tyr Ser Ser Phe Gly Val Cys Ala Asp Gly Ser

545 550 555 560

Ile Ile Ala Val Gln Pro Arg Asn Val Ser Tyr Asp Ser Val Ser Ala

565 570 575

Ile Val Thr Ala Asn Leu Ser Ile Pro Ser Asn Trp Thr Thr Ser Val

580 585 590

Gln Val Glu Tyr Leu Gln Ile Thr Ser Thr Pro Ile Val Val Asp Cys

595 600 605

Ser Thr Tyr Val Cys Asn Gly Asn Val Arg Cys Val Glu Leu Leu Lys

610 615 620

Gln Tyr Thr Ser Ala Cys Lys Thr Ile Glu Asp Ala Leu Arg Asn Ser

625 630 635 640

Ala Arg Leu Glu Ser Ala Asp Val Ser Glu Met Leu Thr Phe Asp Lys

645 650 655

Lys Ala Phe Thr Leu Ala Asn Val Ser Ser Phe Gly Asp Tyr Asn Leu

660 665 670

Ser Ser Val Ile Pro Ser Leu Pro Thr Ser Gly Ser Arg Val Ala Gly

675 680 685

Arg Ser Ala Ile Glu Asp Ile Leu Phe Ser Lys Leu Val Thr Ser Gly

690 695 700

Leu Gly Thr Val Asp Ala Asp Tyr Lys Lys Cys Thr Lys Gly Leu Ser

705 710 715 720

Ile Ala Asp Leu Ala Cys Ala Gln Tyr Tyr Asn Gly Ile Met Val Leu

725 730 735

Pro Gly Val Ala Asp Ala Glu Arg Met Ala Met Tyr Thr Gly Ser Leu

740 745 750

Ile Gly Gly Ile Ala Leu Gly Gly Leu Thr Ser Ala Val Ser Ile Pro

755 760 765

Phe Ser Leu Ala Ile Gln Ala Arg Leu Asn Tyr Val Ala Leu Gln Thr

770 775 780

Asp Val Leu Gln Glu Asn Gln Lys Ile Leu Ala Ala Ser Phe Asn Lys

785 790 795 800

Ala Met Thr Asn Ile Val Asp Ala Phe Thr Gly Val Asn Asp Ala Ile

805 810 815

Thr Gln Thr Ser Gln Ala Leu Gln Thr Val Ala Thr Ala Leu Asn Lys

820 825 830

Ile Gln Asp Val Val Asn Gln Gln Gly Asn Ser Leu Asn His Leu Thr

835 840 845

Ser Gln Leu Arg Gln Asn Phe Gln Ala Ile Ser Ser Ser Ile Gln Ala

850 855 860

Ile Tyr Asp Arg Leu Asp Thr Ile Gln Ala Asp Gln Gln Val Asp Arg

865 870 875 880

Leu Ile Thr Gly Arg Leu Ala Ala Leu Asn Val Phe Val Ser His Thr

885 890 895

Leu Thr Lys Tyr Thr Glu Val Arg Ala Ser Arg Gln Leu Ala Gln Gln

900 905 910

Lys Val Asn Glu Cys Val Lys Ser Gln Ser Lys Arg Tyr Gly Phe Cys

915 920 925

Gly Asn Gly Thr His Ile Phe Ser Ile Val Asn Ala Ala Pro Glu Gly

930 935 940

Leu Val Phe Leu His Thr Val Leu Leu Pro Thr Gln Tyr Lys Asp Val

945 950 955 960

Glu Ala Trp Ser Gly Leu Cys Val Asp Gly Thr Asn Gly Tyr Val Leu

965 970 975

Arg Gln Pro Asn Leu Ala Leu Tyr Lys Glu Gly Asn Tyr Tyr Arg Ile

980 985 990

Thr Ser Arg Ile Met Phe Glu Pro Arg Ile Pro Thr Met Ala Asp Phe

995 1000 1005

Val Gln Ile Glu Asn Cys Asn Val Thr Phe Val Asn Ile Ser Arg Ser

1010 1015 1020

Glu Leu Gln Thr Ile Val Pro Glu Tyr Ile Asp Val Asn Lys Thr Leu

1025 1030 1035 1040

Gln Glu Leu Ser Tyr Lys Leu Pro Asn Tyr Thr Val Pro Asp Leu Val

1045 1050 1055

Val Glu Gln Tyr Asn Gln Thr Ile Leu Asn Leu Thr Ser Glu Ile Ser

1060 1065 1070

Thr Leu Glu Asn Lys Ser Ala Glu Leu Asn Tyr Thr Val Gln Lys Leu

1075 1080 1085

Gln Thr Leu Ile Asp Asn Ile Asn Ser Thr Leu Val Asp Leu Lys Trp

1090 1095 1100

Leu Asn Arg Val Glu Thr Tyr Ile Lys Trp Pro Trp Trp Val Trp Leu

1105 1110 1115 1120

Cys Ile Ser Val Val Leu Ile Phe Val Val Ser Met Leu Leu Leu Cys

1125 1130 1135

Cys Cys Ser Thr Gly Cys Cys Gly Phe Phe Ser Cys Phe Ala Ser Ser

1140 1145 1150

Ile Arg Gly Cys Cys Glu Ser Thr Lys Leu Pro Tyr Tyr Asp Val Glu

1155 1160 1165

Lys Ile His Ile Gln

1170

<210> 160

<211> 1346

<212> PRT

<213> OC43 coronavirus

<400> 160

Val Ile Gly Asp Leu Asn Cys Thr Leu Asp Pro Arg Leu Lys Gly Ser

1 5 10 15

Phe Asn Asn Arg Asp Thr Gly Pro Pro Ser Ile Ser Ile Asp Thr Val

20 25 30

Asp Val Thr Asn Gly Leu Gly Thr Tyr Tyr Val Leu Asp Arg Val Tyr

35 40 45

Leu Asn Thr Thr Leu Phe Leu Asn Gly Tyr Tyr Pro Thr Ser Gly Ser

50 55 60

Thr Tyr Arg Asn Met Ala Leu Lys Gly Thr Asp Leu Leu Ser Thr Leu

65 70 75 80

Trp Phe Lys Pro Pro Phe Leu Ser Asp Phe Ile Asn Gly Ile Phe Ala

85 90 95

Lys Val Lys Asn Thr Lys Val Phe Lys Asp Gly Val Met Tyr Ser Glu

100 105 110

Phe Pro Ala Ile Thr Ile Gly Ser Thr Phe Val Asn Thr Ser Tyr Ser

115 120 125

Val Val Val Gln Pro Arg Thr Ile Asn Ser Thr Gln Asp Gly Val Asn

130 135 140

Lys Leu Gln Gly Leu Leu Glu Val Ser Val Cys Gln Tyr Asn Met Cys

145 150 155 160

Glu Tyr Pro His Thr Ile Cys His Pro Asn Leu Gly Asn His Phe Lys

165 170 175

Glu Leu Trp His Tyr Asp Thr Gly Val Val Ser Cys Leu Tyr Lys Arg

180 185 190

Asn Phe Thr Tyr Asp Val Asn Ala Thr Tyr Leu Tyr Phe His Phe Tyr

195 200 205

Gln Glu Gly Gly Thr Phe Tyr Ala Tyr Phe Thr Asp Thr Gly Phe Val

210 215 220

Thr Lys Phe Leu Phe Asn Val Tyr Leu Gly Met Ala Leu Ser His Tyr

225 230 235 240

Tyr Val Met Pro Leu Thr Cys Ile Arg Arg Pro Lys Asp Gly Phe Ser

245 250 255

Leu Glu Tyr Trp Val Thr Pro Leu Thr Pro Arg Gln Tyr Leu Leu Ala

260 265 270

Phe Asn Gln Asp Gly Ile Ile Phe Asn Ala Val Asp Cys Met Ser Asp

275 280 285

Phe Met Ser Glu Ile Lys Cys Lys Thr Gln Ser Ile Ala Pro Pro Thr

290 295 300

Gly Val Tyr Glu Leu Asn Gly Tyr Thr Val Gln Pro Val Ala Asp Val

305 310 315 320

Tyr Arg Arg Lys Pro Asp Leu Pro Asn Cys Asn Ile Glu Ala Trp Leu

325 330 335

Asn Asp Lys Ser Val Pro Ser Pro Leu Asn Trp Glu Arg Lys Thr Phe

340 345 350

Ser Asn Cys Asn Phe Asn Met Ser Ser Leu Met Ser Phe Ile Gln Ala

355 360 365

Asp Ser Phe Thr Cys Asn Asn Ile Asp Ala Ala Lys Ile Tyr Gly Met

370 375 380

Cys Phe Ser Ser Ile Thr Ile Asp Lys Phe Ala Ile Pro Asn Arg Arg

385 390 395 400

Lys Val Asp Leu Gln Leu Gly Asn Leu Gly Tyr Leu Gln Ser Ser Asn

405 410 415

Tyr Arg Ile Asp Thr Thr Ala Thr Ser Cys Gln Leu Tyr Tyr Asn Leu

420 425 430

Pro Ala Ala Asn Val Ser Val Ser Arg Phe Asn Pro Ser Thr Trp Asn

435 440 445

Lys Arg Phe Gly Phe Ile Glu Asp Ser Val Phe Val Pro Gln Pro Thr

450 455 460

Gly Val Phe Thr Asn His Ser Val Val Tyr Ala Gln His Cys Phe Lys

465 470 475 480

Ala Pro Lys Asn Phe Cys Pro Cys Ser Ser Cys Ser Cys Pro Gly Lys

485 490 495

Asn Asn Gly Ile Gly Thr Cys Pro Ala Gly Thr Asn Ser Leu Thr Cys

500 505 510

Asp Asn Leu Cys Thr Leu Asp Pro Ile Thr Leu Lys Ala Pro Asp Thr

515 520 525

Tyr Lys Cys Pro Gln Ser Lys Ser Leu Val Gly Ile Gly Glu His Cys

530 535 540

Ser Gly Leu Ala Val Lys Ser Asp Tyr Cys Gly Asn Asn Ser Cys Thr

545 550 555 560

Cys Gln Pro Gln Ala Phe Leu Gly Trp Ser Ala Asp Ser Cys Leu Gln

565 570 575

Gly Asp Lys Cys Asn Ile Phe Ala Asn Phe Ile Leu His Asp Val Asn

580 585 590

Asn Gly Leu Thr Cys Ser Thr Asp Leu Gln Lys Ala Asn Thr Glu Ile

595 600 605

Glu Leu Gly Val Cys Val Asn Tyr Asp Leu Tyr Gly Ile Ser Gly Gln

610 615 620

Gly Ile Phe Val Glu Val Asn Ala Thr Tyr Tyr Asn Ser Trp Gln Asn

625 630 635 640

Leu Leu Tyr Asp Ser Asn Gly Asn Leu Tyr Gly Phe Arg Asp Tyr Ile

645 650 655

Thr Asn Arg Thr Phe Met Ile His Ser Cys Tyr Ser Gly Arg Val Ser

660 665 670

Ala Ala Tyr His Ala Asn Ser Ser Glu Pro Ala Leu Leu Phe Arg Asn

675 680 685

Ile Lys Cys Asn Tyr Val Phe Asn Asn Ser Leu Thr Arg Gln Leu Gln

690 695 700

Pro Ile Asn Tyr Ser Phe Asp Ser Tyr Leu Gly Cys Val Val Asn Ala

705 710 715 720

Tyr Asn Ser Thr Ala Ile Ser Val Gln Thr Cys Asp Leu Thr Val Gly

725 730 735

Ser Gly Tyr Cys Val Asp Tyr Ser Lys Asn Arg Arg Ser Arg Arg Ala

740 745 750

Ile Thr Thr Gly Tyr Arg Phe Thr Asn Phe Glu Pro Phe Thr Val Asn

755 760 765

Ser Val Asn Asp Ser Leu Glu Pro Val Gly Gly Leu Tyr Glu Ile Gln

770 775 780

Ile Pro Ser Glu Phe Thr Ile Gly Asn Met Glu Glu Phe Ile Gln Thr

785 790 795 800

Ser Ser Pro Lys Val Thr Ile Asp Cys Ala Ala Phe Val Cys Gly Asp

805 810 815

Tyr Ala Ala Cys Lys Leu Gln Leu Val Glu Tyr Gly Ser Phe Cys Asp

820 825 830

Asn Ile Asn Ala Ile Leu Thr Glu Val Asn Glu Leu Leu Asp Thr Thr

835 840 845

Gln Leu Gln Val Ala Asn Ser Leu Met Asn Gly Val Thr Leu Ser Thr

850 855 860

Lys Leu Lys Asp Gly Val Asn Phe Asn Val Asp Asp Ile Asn Phe Ser

865 870 875 880

Pro Val Leu Gly Cys Leu Gly Ser Glu Cys Ser Lys Ala Ser Ser Arg

885 890 895

Ser Ala Ile Glu Asp Leu Leu Phe Asp Lys Val Lys Leu Ser Asp Val

900 905 910

Gly Phe Val Glu Ala Tyr Asn Asn Cys Thr Gly Gly Ala Glu Ile Arg

915 920 925

Asp Leu Ile Cys Val Gln Ser Tyr Lys Gly Ile Lys Val Leu Pro Pro

930 935 940

Leu Leu Ser Glu Asn Gln Ile Ser Gly Tyr Thr Leu Ala Ala Thr Ser

945 950 955 960

Ala Ser Leu Phe Pro Pro Trp Thr Ala Ala Ala Gly Val Pro Phe Tyr

965 970 975

Leu Asn Val Gln Tyr Arg Ile Asn Gly Leu Gly Val Thr Met Asp Val

980 985 990

Leu Ser Gln Asn Gln Lys Leu Ile Ala Asn Ala Phe Asn Asn Ala Leu

995 1000 1005

His Ala Ile Gln Gln Gly Phe Asp Ala Thr Asn Ser Ala Leu Val Lys

1010 1015 1020

Ile Gln Ala Val Val Asn Ala Asn Ala Glu Ala Leu Asn Asn Leu Leu

1025 1030 1035 1040

Gln Gln Leu Ser Asn Arg Phe Gly Ala Ile Ser Ala Ser Leu Gln Glu

1045 1050 1055

Ile Leu Ser Arg Leu Asp Ala Leu Glu Ala Glu Ala Gln Ile Asp Arg

1060 1065 1070

Leu Ile Asn Gly Arg Leu Thr Ala Leu Asn Ala Tyr Val Ser Gln Gln

1075 1080 1085

Leu Ser Asp Ser Thr Leu Val Lys Phe Ser Ala Ala Gln Ala Met Glu

1090 1095 1100

Lys Val Asn Glu Cys Val Lys Ser Gln Ser Ser Arg Ile Asn Phe Cys

1105 1110 1115 1120

Gly Asn Gly Asn His Ile Ile Ser Leu Val Gln Asn Ala Pro Tyr Gly

1125 1130 1135

Leu Tyr Phe Ile His Phe Asn Tyr Val Pro Thr Lys Tyr Val Thr Ala

1140 1145 1150

Lys Val Ser Pro Gly Leu Cys Ile Ala Gly Asn Arg Gly Ile Ala Pro

1155 1160 1165

Lys Ser Gly Tyr Phe Val Asn Val Asn Asn Thr Trp Met Tyr Thr Gly

1170 1175 1180

Ser Gly Tyr Tyr Tyr Pro Glu Pro Ile Thr Glu Asn Asn Val Val Val

1185 1190 1195 1200

Met Ser Thr Cys Ala Val Asn Tyr Thr Lys Ala Pro Tyr Val Met Leu

1205 1210 1215

Asn Thr Ser Ile Pro Asn Leu Pro Asp Phe Lys Glu Glu Leu Asp Gln

1220 1225 1230

Trp Phe Lys Asn Gln Thr Ser Val Ala Pro Asp Leu Ser Leu Asp Tyr

1235 1240 1245

Ile Asn Val Thr Phe Leu Asp Leu Gln Val Glu Met Asn Arg Leu Gln

1250 1255 1260

Glu Ala Ile Lys Val Leu Asn His Ser Tyr Ile Asn Leu Lys Asp Ile

1265 1270 1275 1280

Gly Thr Tyr Glu Tyr Tyr Val Lys Trp Pro Trp Tyr Val Trp Leu Leu

1285 1290 1295

Ile Cys Leu Ala Gly Val Ala Met Leu Val Leu Leu Phe Phe Ile Cys

1300 1305 1310

Cys Cys Thr Gly Cys Gly Thr Ser Cys Phe Lys Lys Cys Gly Gly Cys

1315 1320 1325

Cys Asp Asp Tyr Thr Gly Tyr Gln Glu Leu Val Ile Lys Thr Ser His

1330 1335 1340

Asp Asp

1345

<210> 161

<211> 1157

<212> PRT

<213> 229E coronavirus

<400> 161

Gln Thr Thr Asn Gly Leu Asn Thr Ser Tyr Ser Val Cys Asn Gly Cys

1 5 10 15

Val Gly Tyr Ser Glu Asn Val Phe Ala Val Glu Ser Gly Gly Tyr Ile

20 25 30

Pro Ser Asp Phe Ala Phe Asn Asn Trp Phe Leu Leu Thr Asn Thr Ser

35 40 45

Ser Val Val Asp Gly Val Val Arg Ser Phe Gln Pro Leu Leu Leu Asn

50 55 60

Cys Leu Trp Ser Val Ser Gly Leu Arg Phe Thr Thr Gly Phe Val Tyr

65 70 75 80

Phe Asn Gly Thr Gly Arg Gly Asp Cys Lys Gly Phe Ser Ser Asp Val

85 90 95

Leu Ser Asp Val Ile Arg Tyr Asn Leu Asn Phe Glu Glu Asn Leu Arg

100 105 110

Arg Gly Thr Ile Leu Phe Lys Thr Ser Tyr Gly Val Val Val Phe Tyr

115 120 125

Cys Thr Asn Asn Thr Leu Val Ser Gly Asp Ala His Ile Pro Phe Gly

130 135 140

Thr Val Leu Gly Asn Phe Tyr Cys Phe Val Asn Thr Thr Ile Gly Asn

145 150 155 160

Glu Thr Thr Ser Ala Phe Val Gly Ala Leu Pro Lys Thr Val Arg Glu

165 170 175

Phe Val Ile Ser Arg Thr Gly His Phe Tyr Ile Asn Gly Tyr Arg Tyr

180 185 190

Phe Thr Leu Gly Asn Val Glu Ala Val Asn Phe Asn Val Thr Thr Ala

195 200 205

Glu Thr Thr Asp Phe Cys Thr Val Ala Leu Ala Ser Tyr Ala Asp Val

210 215 220

Leu Val Asn Val Ser Gln Thr Ser Ile Ala Asn Ile Ile Tyr Cys Asn

225 230 235 240

Ser Val Ile Asn Arg Leu Arg Cys Asp Gln Leu Ser Phe Asp Val Pro

245 250 255

Asp Gly Phe Tyr Ser Thr Ser Pro Ile Gln Ser Val Glu Leu Pro Val

260 265 270

Ser Ile Val Ser Leu Pro Val Tyr His Lys His Thr Phe Ile Val Leu

275 280 285

Tyr Val Asp Phe Lys Pro Gln Ser Gly Gly Gly Lys Cys Phe Asn Cys

290 295 300

Tyr Pro Ala Gly Val Asn Ile Thr Leu Ala Asn Phe Asn Glu Thr Lys

305 310 315 320

Gly Pro Leu Cys Val Asp Thr Ser His Phe Thr Thr Lys Tyr Val Ala

325 330 335

Val Tyr Ala Asn Val Gly Arg Trp Ser Ala Ser Ile Asn Thr Gly Asn

340 345 350

Cys Pro Phe Ser Phe Gly Lys Val Asn Asn Phe Val Lys Phe Gly Ser

355 360 365

Val Cys Phe Ser Leu Lys Asp Ile Pro Gly Gly Cys Ala Met Pro Ile

370 375 380

Val Ala Asn Trp Ala Tyr Ser Lys Tyr Tyr Thr Ile Gly Ser Leu Tyr

385 390 395 400

Val Ser Trp Ser Asp Gly Asp Gly Ile Thr Gly Val Pro Gln Pro Val

405 410 415

Glu Gly Val Ser Ser Phe Met Asn Val Thr Leu Asp Lys Cys Thr Lys

420 425 430

Tyr Asn Ile Tyr Asp Val Ser Gly Val Gly Val Ile Arg Val Ser Asn

435 440 445

Asp Thr Phe Leu Asn Gly Ile Thr Tyr Thr Ser Thr Ser Gly Asn Leu

450 455 460

Leu Gly Phe Lys Asp Val Thr Lys Gly Thr Ile Tyr Ser Ile Thr Pro

465 470 475 480

Cys Asn Pro Pro Asp Gln Leu Val Val Tyr Gln Gln Ala Val Val Gly

485 490 495

Ala Met Leu Ser Glu Asn Phe Thr Ser Tyr Gly Phe Ser Asn Val Val

500 505 510

Glu Leu Pro Lys Phe Phe Tyr Ala Ser Asn Gly Thr Tyr Asn Cys Thr

515 520 525

Asp Ala Val Leu Thr Tyr Ser Ser Phe Gly Val Cys Ala Asp Gly Ser

530 535 540

Ile Ile Ala Val Gln Pro Arg Asn Val Ser Tyr Asp Ser Val Ser Ala

545 550 555 560

Ile Val Thr Ala Asn Leu Ser Ile Pro Ser Asn Trp Thr Thr Ser Val

565 570 575

Gln Val Glu Tyr Leu Gln Ile Thr Ser Thr Pro Ile Val Val Asp Cys

580 585 590

Ser Thr Tyr Val Cys Asn Gly Asn Val Arg Cys Val Glu Leu Leu Lys

595 600 605

Gln Tyr Thr Ser Ala Cys Lys Thr Ile Glu Asp Ala Leu Arg Asn Ser

610 615 620

Ala Arg Leu Glu Ser Ala Asp Val Ser Glu Met Leu Thr Phe Asp Lys

625 630 635 640

Lys Ala Phe Thr Leu Ala Asn Val Ser Ser Phe Gly Asp Tyr Asn Leu

645 650 655

Ser Ser Val Ile Pro Ser Leu Pro Thr Ser Gly Ser Arg Val Ala Gly

660 665 670

Arg Ser Ala Ile Glu Asp Ile Leu Phe Ser Lys Leu Val Thr Ser Gly

675 680 685

Leu Gly Thr Val Asp Ala Asp Tyr Lys Lys Cys Thr Lys Gly Leu Ser

690 695 700

Ile Ala Asp Leu Ala Cys Ala Gln Tyr Tyr Asn Gly Ile Met Val Leu

705 710 715 720

Pro Gly Val Ala Asp Ala Glu Arg Met Ala Met Tyr Thr Gly Ser Leu

725 730 735

Ile Gly Gly Ile Ala Leu Gly Gly Leu Thr Ser Ala Val Ser Ile Pro

740 745 750

Phe Ser Leu Ala Ile Gln Ala Arg Leu Asn Tyr Val Ala Leu Gln Thr

755 760 765

Asp Val Leu Gln Glu Asn Gln Lys Ile Leu Ala Ala Ser Phe Asn Lys

770 775 780

Ala Met Thr Asn Ile Val Asp Ala Phe Thr Gly Val Asn Asp Ala Ile

785 790 795 800

Thr Gln Thr Ser Gln Ala Leu Gln Thr Val Ala Thr Ala Leu Asn Lys

805 810 815

Ile Gln Asp Val Val Asn Gln Gln Gly Asn Ser Leu Asn His Leu Thr

820 825 830

Ser Gln Leu Arg Gln Asn Phe Gln Ala Ile Ser Ser Ser Ile Gln Ala

835 840 845

Ile Tyr Asp Arg Leu Asp Thr Ile Gln Ala Asp Gln Gln Val Asp Arg

850 855 860

Leu Ile Thr Gly Arg Leu Ala Ala Leu Asn Val Phe Val Ser His Thr

865 870 875 880

Leu Thr Lys Tyr Thr Glu Val Arg Ala Ser Arg Gln Leu Ala Gln Gln

885 890 895

Lys Val Asn Glu Cys Val Lys Ser Gln Ser Lys Arg Tyr Gly Phe Cys

900 905 910

Gly Asn Gly Thr His Ile Phe Ser Ile Val Asn Ala Ala Pro Glu Gly

915 920 925

Leu Val Phe Leu His Thr Val Leu Leu Pro Thr Gln Tyr Lys Asp Val

930 935 940

Glu Ala Trp Ser Gly Leu Cys Val Asp Gly Thr Asn Gly Tyr Val Leu

945 950 955 960

Arg Gln Pro Asn Leu Ala Leu Tyr Lys Glu Gly Asn Tyr Tyr Arg Ile

965 970 975

Thr Ser Arg Ile Met Phe Glu Pro Arg Ile Pro Thr Met Ala Asp Phe

980 985 990

Val Gln Ile Glu Asn Cys Asn Val Thr Phe Val Asn Ile Ser Arg Ser

995 1000 1005

Glu Leu Gln Thr Ile Val Pro Glu Tyr Ile Asp Val Asn Lys Thr Leu

1010 1015 1020

Gln Glu Leu Ser Tyr Lys Leu Pro Asn Tyr Thr Val Pro Asp Leu Val

1025 1030 1035 1040

Val Glu Gln Tyr Asn Gln Thr Ile Leu Asn Leu Thr Ser Glu Ile Ser

1045 1050 1055

Thr Leu Glu Asn Lys Ser Ala Glu Leu Asn Tyr Thr Val Gln Lys Leu

1060 1065 1070

Gln Thr Leu Ile Asp Asn Ile Asn Ser Thr Leu Val Asp Leu Lys Trp

1075 1080 1085

Leu Asn Arg Val Glu Thr Tyr Ile Lys Trp Pro Trp Trp Val Trp Leu

1090 1095 1100

Cys Ile Ser Val Val Leu Ile Phe Val Val Ser Met Leu Leu Leu Cys

1105 1110 1115 1120

Cys Cys Ser Thr Gly Cys Cys Gly Phe Phe Ser Cys Phe Ala Ser Ser

1125 1130 1135

Ile Arg Gly Cys Cys Glu Ser Thr Lys Leu Pro Tyr Tyr Asp Val Glu

1140 1145 1150

Lys Ile His Ile Gln

1155

<210> 162

<211> 56

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-OC43-COV wtTMCT-AA

<400> 162

Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val

1 5 10 15

Leu Leu Phe Phe Ile Cys Cys Cys Thr Gly Cys Gly Thr Ser Cys Phe

20 25 30

Lys Lys Cys Gly Gly Cys Cys Asp Asp Tyr Thr Gly Tyr Gln Glu Leu

35 40 45

Val Ile Lys Thr Ser His Asp Asp

50 55

<210> 163

<211> 40

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-OC43-COV H5iTMCT-AA

<400> 163

Trp Tyr Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala

1 5 10 15

Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

20 25 30

Ser Leu Gln Cys Arg Ile Cys Ile

35 40

<210> 164

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-OC43-COV H5iCT-AA

<400> 164

Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val

1 5 10 15

Leu Leu Phe Phe Ile Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 165

<211> 34

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-OC43-COV H5iCT (V4) -AA

<400> 165

Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val

1 5 10 15

Leu Leu Phe Phe Ile Cys Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile

20 25 30

Cys Ile

<210> 166

<211> 37

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-OC43-COV H1cCT-AA

<400> 166

Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val

1 5 10 15

Leu Leu Phe Phe Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln

20 25 30

Cys Arg Ile Cys Ile

35

<210> 167

<211> 58

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-229E-wtTMCT-AA

<400> 167

Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val Ser

1 5 10 15

Met Leu Leu Leu Cys Cys Cys Ser Thr Gly Cys Cys Gly Phe Phe Ser

20 25 30

Cys Phe Ala Ser Ser Ile Arg Gly Cys Cys Glu Ser Thr Lys Leu Pro

35 40 45

Tyr Tyr Asp Val Glu Lys Ile His Ile Gln

50 55

<210> 168

<211> 40

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-229E-H5iTMCT-AA

<400> 168

Trp Trp Gln Ile Leu Ser Ile Tyr Ser Thr Val Ala Ser Ser Leu Ala

1 5 10 15

Leu Ala Ile Met Met Ala Gly Leu Ser Leu Trp Met Cys Ser Asn Gly

20 25 30

Ser Leu Gln Cys Arg Ile Cys Ile

35 40

<210> 169

<211> 36

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-229E-H5iCT-AA

<400> 169

Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val Ser

1 5 10 15

Met Leu Leu Leu Ser Leu Trp Met Cys Ser Asn Gly Ser Leu Gln Cys

20 25 30

Arg Ile Cys Ile

35

<210> 170

<211> 33

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-229E-H5iCT (V4) -AA

<400> 170

Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val Ser

1 5 10 15

Met Leu Leu Leu Cys Cys Ser Asn Gly Ser Leu Gln Cys Arg Ile Cys

20 25 30

Ile

<210> 171

<211> 35

<212> PRT

<213> artificial sequence

<220>

<223> TMCT region of modified PDI-229E-H1cCT-AA

<400> 171

Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val Ser Met

1 5 10 15

Leu Leu Leu Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln Cys Arg

20 25 30

Ile Cys Ile

35

<210> 172

<211> 34

<212> PRT

<213> artificial sequence

<220>

<223> modified OC43-CoV S protein, TM/CT region of Xn having intermediate peptide sequence

<220>

<221> MISC_FEATURE

<222> (22)..(22)

<223> Xaa can be any combination of 0 to 10 amino acids

<220>

<221> misc_feature

<222> (28)..(29)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (31)..(31)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (22)..(22)

<223> The 'Xaa' at location 22 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (28)..(28)

<223> The 'Xaa' at location 28 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (29)..(29)

<223> The 'Xaa' at location 29 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (31)..(31)

<223> The 'Xaa' at location 31 stands for Gln, Arg, Pro, or Leu.

<400> 172

Trp Tyr Val Trp Leu Leu Ile Cys Leu Ala Gly Val Ala Met Leu Val

1 5 10 15

Leu Leu Phe Phe Ile Xaa Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile

20 25 30

Cys Ile

<210> 173

<211> 33

<212> PRT

<213> artificial sequence

<220>

<223> modified OC43-CoV S protein, TM/CT region with intermediate peptide sequence Xn

<220>

<221> MISC_FEATURE

<222> (21)..(21)

<223> Xaa can be any combination of 0 to 10 amino acids

<220>

<221> misc_feature

<222> (27)..(28)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (30)..(30)

<223> Xaa can be any naturally occurring amino acid

<220>

<221> misc_feature

<222> (21)..(21)

<223> The 'Xaa' at location 21 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (27)..(27)

<223> The 'Xaa' at location 27 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (28)..(28)

<223> The 'Xaa' at location 28 stands for Gln, Arg, Pro, or Leu.

<220>

<221> misc_feature

<222> (30)..(30)

<223> The 'Xaa' at location 30 stands for Gln, Arg, Pro, or Leu.

<400> 173

Trp Trp Val Trp Leu Cys Ile Ser Val Val Leu Ile Phe Val Val Ser

1 5 10 15

Met Leu Leu Leu Xaa Cys Ser Asn Gly Ser Xaa Xaa Cys Xaa Ile Cys

20 25 30

Ile

Claims

1. A modified coronavirus S protein comprising, in order:

an extracellular domain derived from the coronavirus S protein;

2. The modified coronavirus S protein of claim 1, wherein the TM is directly fused to the CT.

3. The modified coronavirus S protein of claim 1, wherein the TM is a chimeric TM comprising an N-terminal sequence derived from the coronavirus S protein TM and a C-terminal sequence derived from the influenza HA protein TM.

4. The modified coronavirus S protein of claim 3, wherein the chimeric TM comprises an N-terminal sequence derived from the coronavirus S protein TM comprising a sequence corresponding to SEQ ID NO:18 or SEQ ID NO:169, or at least 20 amino acids corresponding to amino acids 1-20 of SEQ ID NO:118 or SEQ ID NO:164, or at least 21 amino acids corresponding to amino acids 1-21 of SEQ ID NO:123, at least 22 amino acids 1-22, and one or more amino acids from the C-terminus of the influenza HA protein TM.

5. The modified coronavirus S protein of claim 4, wherein the one or more amino acids derived from the C-terminus of the influenza HA protein TM are selected from AGL or conservative substitutions of AGL, MAGL or conservative substitutions of MAGL.

6. The modified coronavirus S protein of claim 1, wherein the CT is a chimeric CT comprising an N-terminal sequence derived from the coronavirus S protein CT and a C-terminal sequence derived from the influenza HA protein CT.

7. The modified coronavirus S protein of claim 6, wherein the chimeric CT comprises a C-terminal sequence derived from the influenza HA protein CT comprising a sequence corresponding to SEQ ID NO: 18. 126, 128, 129, 130 or 131, or amino acids 27-37 corresponding to SEQ ID NO:127, and one or more than one amino acid from the N-terminus of the coronavirus S protein CT.

8. The modified coronavirus S protein of claim 7, wherein the one or more amino acids from the N-terminus of the coronavirus S protein CT are selected from a C or a conservative substitution of C, a CC or a conservative substitution of CC, or a CCM or a conservative substitution of CCM.

9. The modified coronavirus S protein of claim 3, wherein the chimeric TM comprises a sequence corresponding to SEQ ID NO:18 or SEQ ID NO:169, or amino acids 1-20 corresponding to SEQ ID NO:118 or SEQ ID NO:164, or amino acids corresponding to amino acids 1-21 of SEQ ID NO:123 amino acids 1-22.

10. The modified coronavirus S protein of claim 4, wherein the chimeric CT comprises a sequence corresponding to SEQ ID NO: 18. 126, 128, 129, 130 or 131 amino acids 27-37, or SEQ ID NO:127, amino acids 27-36.

11. The modified coronavirus S protein of claim 1, wherein the chimeric TMCT comprises a chimeric TM comprising a sequence corresponding to SEQ ID NO:18 or SEQ ID NO:169, or amino acids 1-20 corresponding to SEQ ID NO:118 or SEQ ID NO:164, or amino acids corresponding to amino acids 1-21 of SEQ ID NO:123, said chimeric CT comprises amino acids corresponding to amino acids 1-22 of SEQ ID NO: 18. 126, 128, 129, 130 or 131, amino acids 27-37, corresponding to SEQ ID NO:127 from amino acids 27 to 36 or a combination thereof.

12. The modified S protein of any one of claims 1-11, wherein the S protein comprises one or more amino acid substitutions when compared to the wild-type coronavirus S protein amino acid sequence.

13. The modified S protein of claim 12, wherein the one or more amino acid substitutions comprise:

i) Limiting substitution of processing at the cleavage site between the S1 subunit and the S2 subunit;

ii) one or more amino acids are replaced with one or more proline; or (b)

iii) Substitutions that limit processing at the cleavage site between the S1 subunit and the S2 subunit, and one or more amino acid substitutions to one or more proline.

14. The modified S protein of claim 12 or 13, wherein the amino acid sequence corresponding to SEQ ID NO:2, said one or more amino acid substitutions corresponding to the amino acids at positions 971 and 972 when compared to the reference amino acid sequence.

15. The modified S protein of claim 12 or 13, wherein the amino acid sequence corresponding to SEQ ID NO:2, said one or more amino acid substitutions corresponding to amino acids at positions 802, 927, 971 and 972.

16. The modified S protein of claim 14 or 15, wherein the amino acid sequence corresponding to SEQ ID NO:2, the modified S protein further comprises one or more amino acid substitutions corresponding to amino acids at positions 667, 668, 670, or a combination thereof.

17. The modified S protein of claim 16, wherein corresponds to the amino acid sequence set forth in SEQ ID NO:2 is glycine or a conservative substitution of glycine, corresponding to amino acid at position 667 of SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to amino acid sequence of SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to SEQ ID NO: amino acid substitutions at positions 971 and 972 of 2 are proline or conservative substitutions of proline.

18. The modified S protein of claim 16, wherein corresponds to the amino acid sequence set forth in SEQ ID NO:2 is glycine or a conservative substitution of glycine, corresponding to amino acid at position 667 of SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to amino acid sequence of SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to SEQ ID NO: amino acid substitutions at positions 802, 927, 971 and 972 of 2 are proline or conservative substitutions of proline.

19. The modified S protein of any one of claims 14-18, wherein the amino acid sequence that hybridizes to SEQ ID NO:2, the modified S protein further comprises an amino acid substitution corresponding to the amino acid at position 923 when compared to the reference amino acid sequence.

20. The modified S protein of claim 19, wherein the amino acid sequence corresponding to SEQ ID NO:2 is glycine or a conservative substitution of glycine, corresponding to amino acid at position 667 of SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to SEQ ID NO:2 is serine or a conservative substitution of serine, corresponding to SEQ ID NO:2 is proline or a conservative substitution of proline and corresponds to amino acid substitutions at positions 802, 927, 971 and 972 of SEQ ID NO: the amino acid substitution at position 923 of 2 is phenylalanine or a conservative substitution of phenylalanine.

21. The modified S protein of any one of claims 12-20, wherein the one or more substitutions maintain the S protein in a pre-fusion state or produce a higher yield of the modified S protein when expressed in a host or host cell when compared to the yield of the corresponding S protein without the one or more substitutions expressed in the host or host cell.

22. The modified S protein of any one of claims 1-21, wherein the S protein comprises an S1 subunit and an S2 subunit, wherein the S2 subunit comprises the chimeric TMCT.

23. The modified S protein of any one of claims 1-22, wherein the influenza HA protein is derived from influenza b or H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, or H16 subtype influenza.

24. The modified S protein of any one of claims 1-23, wherein the coronavirus S protein is derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV, or 229E-CoV.

25. The modified S protein of any one of claims 1-23, wherein the extracellular domain is derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV, or 229E-CoV, the TM or a portion of the TM is derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV, or 229E-CoV, or wherein the extracellular domain and the TM or a portion of the TM are derived from SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43-CoV, or 229E-CoV.

26. The modified S protein of any one of claims 1-25, wherein the TMCT comprises a sequence having about 80% to about 100% identity to: SEQ ID NO: 18. 19, 37, 38, 39, 64, 126, 127, 128, 129, 130, 131, 118, 119, 120, 123, 124, 125, 134, 135, 164, 165, 166, 169, 170, 171, 172 or 173.

27. The modified S protein of any one of claims 1-26, wherein the modified S protein is produced as a precursor protein comprising the modified S protein and a signal peptide.

28. The modified S protein of claim 27, wherein the signal peptide is native or non-native to the modified S protein.

29. The modified S protein of claim 27 or 28, wherein the signal peptide is derived from a signal peptide of a Protein Disulfide Isomerase (PDI).

30. The modified S protein of any one of claims 1-29, wherein the modified S protein comprises a plant-specific N-glycan.

31. The modified S protein of claim 1, wherein the amino acid sequence of the S protein has 80% to 100% identity to: SEQ ID NO: 5. 21, 30, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 95, 96, 97, 108, 109, 110, 144, 145, 146, 155, 156 or 157, or the amino acid of SEQ ID NO:47, amino acids 24-1259, seq ID NO:48, amino acids 25-1259, seq ID NO:49, amino acids 25-1259, seq ID NO:50, amino acids 25-1259, seq ID NO:51, amino acids 25-1259, seq ID NO:52, amino acids 25-1259, seq ID NO:53, amino acids 25-1259, seq ID NO:54, amino acids 25-1259, seq ID NO:55, amino acids 25-1259, seq ID NO:56, amino acids 25-1259, seq ID NO:57, amino acids 25-1259, seq ID NO:58, amino acids 25-1259, seq ID NO:59, amino acids 25-1262, seq ID NO:60, amino acids 25-1261, seq ID NO:61, amino acids 25-1258, or SEQ ID NO:62, amino acids 25-1256, seq ID NO:95, amino acids 25-1243, seq ID NO:96, amino acids 25-1240, seq ID NO:97, amino acids 25-1243, seq ID NO:108, amino acids 25-1341, seq ID NO:109, amino acids 25-1338, seq ID NO:110, or amino acids 25-1341 of SEQ ID NO:144, amino acids 25-1351, seq ID NO:145, amino acids 25-1348, seq ID NO:146, amino acids 25-1351, seq ID NO:155, amino acids 25-1159 of seq ID NO:156, or amino acids 25-1156 of SEQ ID NO:157 from amino acids 25-1159.

32. The modified S protein of any one of claims 1-30, wherein the CT or a portion of the CT has 80% to 100% identity to: SEQ ID NO:15, or SEQ ID NO: 6. 8, 7, 9, 10, 12, 13 or 14, or amino acids 35-50 of SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3, or amino acids 553-568 of SEQ ID NO:18, or amino acids 22-37 of SEQ ID NO:19, amino acids 21-40 of SEQ ID NO:37, or amino acids 21-39 of SEQ ID NO:38, or amino acids 25-36 of SEQ ID NO:39, or amino acids 24-34 of SEQ ID NO: 126. 128, 129, 130 or 131, or amino acids 22-37 of SEQ ID NO:127 from amino acids 22 to 36.

33. The modified S protein of claim 27, wherein the precursor protein has 80% to 100% identity to: SEQ ID NO:1, or amino acids 1-1234 of SEQ ID NO:5, or amino acids 1-1234 of SEQ ID NO:30, amino acids 1-1243, seq ID NO:95, amino acids 1-1227 of seq ID NO:108, amino acids 1-1325, seq ID NO:112, amino acids 1-1216, seq ID NO:113, amino acids 1-1318, seq ID NO:144, amino acids 1-1335, seq ID NO:155, amino acids 1-1143, seq ID NO:158, amino acids 1-1325, seq ID NO:159, and wherein the amino acid sequence of CT has 80% to 100% identity to: SEQ ID NO:15, or SEQ ID NO: 6. 8, 7, 9, 10, 12, 13 or 14, or amino acids 35-50 of SEQ ID NO:11, or amino acids 34-49 of SEQ ID NO:3, amino acids 553-568.

34. A nucleic acid comprising a nucleotide sequence encoding the modified S protein of any one of claims 1-33.

35. A trimer comprising a modified S protein according to any one of claims 1 to 33.

36. A virus-like particle (VLP) comprising the modified S protein of any one of claims 1-33 or the trimer of claim 35.

37. The VLP of claim 36, wherein the VLP further comprises a plant lipid.

38. A composition comprising an effective dose of the modified S protein of any one of claims 1-33, the trimer of claim 35 or the VLP of any one of claims 36-37, and a pharmaceutically acceptable carrier, adjuvant, vehicle or excipient.

39. A vaccine for inducing an immune response, the vaccine comprising an effective dose of the modified S protein of any one of claims 1-33, the trimer of claim 35, the VLP of any one of claims 36-37, or the composition of claim 38.

40. The vaccine of claim 39, wherein the vaccine is a multivalent vaccine comprising a mixture of VLPs.

41. A method for inducing immunity to a coronavirus infection in a subject, the method comprising administering to the subject a composition according to claim 38 or a vaccine according to claim 39 or 40.

42. The method of claim 41, wherein the composition or vaccine is administered to the subject once.

43. The method of claim 41, wherein the composition or vaccine is administered to the subject multiple times.

44. The method of claim 41, wherein the composition or vaccine is administered at an initial dose and one or more subsequent doses are administered between 1 day and 6 months from the initial dose.

45. An antibody or antibody fragment prepared using the composition of claim 38 or the vaccine of claim 39 or 40.

46. A non-human host or host cell comprising the modified S protein of any one of claims 1-33, the trimer of claim 35, the nucleic acid of claim 34, or the VLP of claim 36 or 37.

47. A method of producing a modified S protein in a non-human host or host cell, comprising:

a) Introducing the nucleic acid according to claim 34 into the non-human host or host cell, or providing the non-human host or host cell comprising the nucleic acid according to claim 34, and

b) Culturing the non-human host or host cell under conditions that allow expression of the nucleic acid, thereby producing the modified S protein.

48. A method of producing a virus-like particle (VLP) in a non-human host or host cell, comprising:

49. The method of claim 47 or 48, further comprising step c) harvesting the non-human host or host cell.

50. A method of increasing the production yield of a modified coronavirus S protein in a non-human host or host cell comprising:

a) Introducing the nucleic acid of claim 34 into the host or host cell; or providing a non-human host or host cell comprising the nucleic acid of claim 34; and

b) Culturing the non-human host or host cell under conditions that allow expression of the modified S protein encoded by the nucleic acid, thereby producing the modified S protein in higher yield as compared to a host or host cell expressing an unmodified S protein.

51. A method of increasing the yield of production of virus-like particles (VLPs) in a non-human host or host cell, comprising:

a) Introducing a nucleic acid encoding a modified coronavirus S protein into a non-human host or host cell, said modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein, or

Providing a non-human host or host cell comprising a nucleic acid encoding a modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein; and

b) Culturing the non-human host or host cell under conditions that allow expression of the modified S protein encoded by the nucleic acid, thereby producing VLPs comprising the modified S protein in higher yields than VLP yields in a host of host cells expressing unmodified S protein.

52. A method of producing a virus-like particle (VLP) in a non-human host or host cell, comprising:

a) Introducing a nucleic acid encoding a modified coronavirus S protein into a non-human host or host cell, said modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein; or alternatively

53. The method of any one of claims 48, 51 or 52, wherein said VLP is further extracted and purified from said non-human host or host cell.

54. A VLP produced by the method of claim 48, 51 or 52.

55. A modified S protein produced by the method of claim 47 or 50.

56. The method of any one of claims 47-55 or the non-human host or host cell of claim 46, wherein the non-human host or host cell comprises a plant, plant part, plant cell, fungus, fungal cell, insect cell, animal or animal cell.

57. A composition comprising a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein, and wherein the amino acid sequence of SEQ ID NO:2, the S protein comprises substitutions at positions 667, 668, 670, 971 and 972 when compared to the reference amino acid sequence.

58. A composition comprising a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein, and wherein the S protein comprises a glycine substitution at position 667, a serine substitution at position 668, a serine substitution at position 670, a proline substitution at position 971, and a proline substitution at position 972, the positions corresponding to SEQ ID NO:2, and a reference amino acid sequence.

59. A composition comprising a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified S protein comprising the amino acid sequence of SEQ ID NO:21 or SEQ ID NO:51 amino acids 25-1259.

60. A composition comprising a virus-like particle (VLP), said VLP comprising a modified coronavirus S protein, said modified coronavirus S protein comprising, in order: an extracellular domain, transmembrane and cytoplasmic tail domain (TMCT) derived from a coronavirus S protein, wherein the TMCT is a chimeric TMCT comprising: a transmembrane domain (TM), wherein the TM or a portion of the TM is derived from a coronavirus S protein and a Cytoplasmic Tail (CT), wherein the CT or a portion of the CT is derived from an influenza Hemagglutinin (HA) protein, and wherein the amino acid sequence of SEQ ID NO:2, the S protein comprises substitutions at positions 667, 668, 670, 802, 923, 927, 971 and 972 when compared to the reference amino acid sequence.