KR20240004152A - Vaccine or pharmaceutical composition for preventing or treating COVID-19 using exosomes - Google Patents

Abstract

The present invention relates to a COVID-19 vaccine or pharmaceutical composition for treatment using recombinant exosomes. The recombinant exosome of the present invention exhibits the effect of treatment or vaccine for coronavirus infection by blocking the path through which the spike protein of the coronavirus penetrates into cells through binding to the cell surface receptor ACE2, or is overexpressed on the surface of the exosome. The spike protein can act as an antigen and trigger the production of antibodies against it.

Description

Pharmaceutical composition for COVID-19 vaccine or treatment using exosomes {Vaccine or pharmaceutical composition for preventing or treating COVID-19 using exosomes}

The present invention relates to a vaccine or pharmaceutical composition for treating respiratory diseases caused by coronavirus infections such as COVID-19.

Coronaviruses are enveloped, single-stranded, benign RNA viruses. The coronavirus has a unique flame- or crown-shaped structure with spike proteins, club-shaped protrusions, embedded in its outer shell, and its name comes from the Latin word corona.

Among them, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2; Type 2 severe acute respiratory syndrome coronavirus) is a virus that is contagious to humans and causes coronavirus disease 19 (COVID-19). ARS-CoV-2 appears to have strong genetic similarity to the Bat SARS-like coronavirus and is believed to have originated from this virus. Human-to-human transmission of SARS-CoV-2 has been confirmed by academics, and this coronavirus is mainly transmitted through close contact with respiratory droplets from coughing or nasal discharge, especially within a 2m radius. Another way to contract the infection is by touching your eyes, nose, or mouth after touching a contaminated surface or object.

To date, the development of appropriate solutions to efficiently suppress, treat, or prevent the SARS-CoV-2 viral pathogen has been insufficient, leading to a global need for the development of COVID-19 vaccines and treatments.

Meanwhile, typical exosomes are substances with a double lipid membrane structure with a size of 30-100 nm that are secreted from cells. Because it is derived from cells, it has low immunogenicity and has the same membrane topology as cells, so various membrane proteins can be expressed through genetic manipulation. Exosomes typically have membrane proteins such as CD9, CD63, and LAMP2B expressed on their surfaces.

Numerous documents are referenced and cited throughout this specification. The disclosures of the cited documents are incorporated herein by reference in their entirety to more clearly explain the content of the present invention and the level of technical field to which the present invention pertains.

Republic of Korea Patent Publication No. 10-1913789

The purpose of the present invention is to provide recombinant exosomes for use as an active ingredient in a vaccine or therapeutic composition for coronavirus infection.

Another object of the present invention is to provide a recombinant vector for producing the recombinant exosome and a host cell transformed therewith.

Another object of the present invention is to provide a method for producing the recombinant exosomes for use as an active ingredient in a vaccine or therapeutic composition for coronavirus infection.

Another object of the present invention is to provide a coronavirus infection vaccine composition containing the recombinant exosome as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for treating respiratory diseases caused by coronavirus infection, comprising the recombinant exosome as an active ingredient.

Another object of the present invention is to provide a method for preventing or treating coronavirus infection using the recombinant exosome.

Another object of the present invention is to provide the use of the recombinant exosome as a vaccine or treatment for coronavirus infection.

Another object of the present invention is to provide a use of the recombinant exosome for manufacturing a coronavirus infection vaccine or treatment.

Other objects and advantages of the present invention will become clearer from the following detailed description, claims, and drawings.

One aspect of the present invention is to provide a recombinant exosome on which the angiotensin-converting enzyme 2 (ACE2) protein or the spike protein of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is expressed on the surface.

It is known that the spike protein expressed on the surface of the coronavirus binds to the cell surface receptor (ACE2) and invades the cell.

The present invention provides a recombinant exosome in which ACE2 is overexpressed on the surface, and uses the recombinant exosome to block the path through which the spike protein of the COVID-19 virus penetrates into the cell through binding to the cell surface receptor, ACE2, thereby preventing COVID-19 virus. Achieve the effectiveness of 19 treatments or vaccines.

Additionally, the present invention provides an exosome in which the spike protein is overexpressed on the surface. The spike-exosome binds to the ACE2 of the cell and blocks the spike protein of COVID-19 from binding to the ACE2 of the cell. Additionally, the spike protein overexpressed on the surface of exosomes acts as an antigen and triggers the production of antibodies against it.

In one embodiment, the ACE2 protein may include or consist of an amino acid sequence selected from the group consisting of sequences 1 to 3 in the sequence listing, and is preferably indicated as sequence 2 or 3 in the sequence listing. It may be an ACE2 mutant protein.

*In a preferred embodiment, the ACE2 protein can be fixed to the surface of the exosome by binding to CD9, the surface marker protein of the exosome, more preferably after deleting the fourth transmembrane region of CD9 (CD9△TM4) By linking this with the ACE2 protein, it is possible to produce recombinant exosomes in which ACE2 is overexpressed on the exosome surface.

The recombinant exosome with ACE2 expressed on the surface prepared in this way can bind to the spike protein on the surface of the coronavirus, preventing the virus from penetrating into the cell through binding to the ACE2 protein of the target cell.

In one embodiment, only the S1 unit containing the ACE2 binding domain can be used as the spike protein to minimize the size, and preferably, it may contain or consist of the amino acid sequence shown in sequence number 7 of the sequence list.

In a preferred embodiment, the spike protein can be fixed to the exosome surface by binding to the exosomal membrane protein Lamp2b-S1 or CD9 ^1st TM-S1 protein. The S1-Lamp2b exosome has the N-terminus of the S1 unit exposed to the outside, and the CD9 1 ^st TM-S1 exosome has the C-terminus of the S1 unit exposed to the outside.

Another aspect of the present invention is to provide a recombinant vector comprising a nucleic acid sequence encoding an amino acid sequence selected from the group consisting of sequences 1 to 9 of the sequence listing.

The recombinant vector containing the nucleic acid sequence may be a plasmid vector as an expression vector, preferably pCMV14.

Another aspect of the present invention is to provide a host cell transformed with the above recombinant vector. The host cells may preferably be human cells such as human embryonic kindey cells (HEK cells).

In the present invention, when the recombinant vector containing the nucleic acid sequence is a plasmid vector, microinjection method (Capecchi, MR, Cell, 22:479 (1980); and Harland and Weintraub, J. Cell Biol. 101:1094-1099 (1985) )), calcium phosphate precipitation (Graham, FL et al., Virology , 52:456 (1973); and Chen and Okayama, Mol. Cell. Biol. 7:2745-2752 (1987)), electroporation (Neumann) , E. et al., EMBO J. , 1:841 (1982); and Tur-Kaspa et al., Mol. Cell Biol. , 6:716-718 (1986)), liposome-mediated transfection method (Wong , TK et al., Gene , 10:87 (1980); Nicolau and Sene, Biochim. Biophys. Acta , 721:185-190 (1982); and Nicolau et al., Methods Enzymol. , 149:157-176 ( 1987)), DEAE-dextran treatment (Gopal, Mol. Cell Biol. , 5:1188-1190 (1985)), and gene bombardment (Yang et al., Proc. Natl. Acad. Sci. , 87: Recombinant vectors can be transfected into cells by methods such as 9568-9572 (1990), but are not limited thereto.

Another aspect of the present invention includes culturing the transformed host cell; And to provide a method for producing recombinant exosomes for use as an active ingredient in a vaccine or therapeutic composition for coronavirus infection, comprising the step of isolating and purifying exosomes from the cell culture medium.

The diameter of the recombinant exosomes produced as described above may be 30 to 350 nm, 30 to 300 nm, 30 to 250 nm, 30 to 200 nm, 30 to 150 nm, or 30 to 100 nm.

In one embodiment, the concentration of ACE2 or spike protein contained in the recombinant exosome is 10 pg or more, 50 pg or more, 70 pg or more, 100 pg or more, 150 pg or more, 200 pg or more, 250 pg or more per ug of exosome protein. It may be more than pg, more than 300 pg, more than 350 pg, more than 400 pg, more than 450 pg, or more than 500 pg, preferably 10 to 500 pg, 50 to 400 pg, 70 to 350 pg, or 100 to 300 pg. You can.

Another aspect of the present invention is to provide a vaccine composition for coronavirus infection, comprising recombinant exosomes as an active ingredient.

As used herein, the term coronavirus infection and/or respiratory disease caused by coronavirus infection means severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and/or coronavirus. It includes coronavirus disease 2019 (COVID-19), and preferably, the coronavirus infection may be coronavirus disease 2019 (COVID-19).

In one embodiment, the vaccine composition may further include an adjuvant. An adjuvant or adjuvant component in the broadest sense is, for example, an agent or composition that can be modified pharmacologically or immunologically and improves the efficacy of another agent, such as a drug or vaccine. Typically, this term refers in the context of the present invention to compounds or compositions that act as carriers or auxiliary substances for immunogens and/or other pharmaceutically active compounds. As used herein, this term is to be interpreted in a broad sense and refers to a broad spectrum of substances that can increase the immunogenicity of the antigen incorporated or co-administered with the adjuvant. In the present specification, the adjuvant will preferably enhance the specific immunogenic effect of the recombinant exosomes of the present invention. For example, adjuvants can aid uptake of antigens by antigen-presenting cells, activate macrophages and lymphocytes, and support cytokine production. By altering the immune response, adjuvants can allow for lower doses of an immune interacting agent to increase the effectiveness or safety of a particular dose of the immune interacting agent. For example, adjuvants can increase the effectiveness or safety of certain immune interacting agents by preventing T cell exhaustion. Adjuvants can be divided into, for example, adjuvants, antigen delivery systems, or combinations thereof, including mineral substances, aluminum hydroxide, aluminum phosphate, bacterial extracts (e.g., bacterial lipid sugars, Freund's adjuvant, and/or MDP). , oil-based emulsion, saponin, squalene, potassium aluminum sulfate, calcium hydroxide, TLR agonist, etc., but is not limited thereto.

The recombinant exosome included as an active ingredient in the vaccine composition of the present invention can promote an immune response in vivo and generate antibodies against the coronavirus in the blood of a administered mammal, preferably a human.

Another aspect of the present invention is to provide a pharmaceutical composition for treating respiratory diseases caused by coronavirus infection, comprising recombinant exosomes as an active ingredient. The recombinant exosome included as an active ingredient of the present invention exhibits coronavirus neutralizing efficacy and can therefore be used as a coronavirus treatment agent.

The vaccine composition or therapeutic composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the vaccine or therapeutic composition of the present invention are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, Contains gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not limited to this. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

In some embodiments, the vaccine compositions of the invention may be formulated for parenteral administration, for example, for injection, such as subcutaneous and/or intradermal injection. Accordingly, in some embodiments, the vaccine composition may be liquid (i.e., formulated as a liquid), including solutions, suspensions, dispersions, and gelled liquids. For example, the liquid vaccine composition can be administered to a subject after dissolving the recombinant exosomes of the present invention in a suitable solvent. A suitable solvent can be any solvent that has physiologically acceptable properties and is capable of dissolving exosomes at the desired concentration. The desired concentration may vary depending on the aliquot to be administered (i.e., infused) and the single dose desired.

The therapeutic pharmaceutical composition of the present invention can be administered orally or parenterally, and the appropriate dosage of the pharmaceutical composition of the present invention is the formulation method, administration method, patient's age, weight, sex, pathological condition, food, and administration time. , it can be prescribed in various ways depending on factors such as route of administration, excretion rate, and reaction sensitivity.

The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating it using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the formulation may be in the form of a solution, suspension, syrup or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet or capsule, and may additionally contain a dispersant or stabilizer.

The recombinant exosome of the present invention exhibits the effect of treatment or vaccine for coronavirus infection by blocking the path through which the spike protein of the coronavirus penetrates into cells through binding to the cell surface receptor, ACE2, or is overexpressed on the surface of the exosome. The spike protein can act as an antigen and trigger the production of antibodies against it.

Figure 1 shows an overview of the technology in which a recombinant exosome overexpressing sACE2 binds to the spike protein on the surface of the virus, thereby inhibiting the virus from penetrating into the cell through binding to the ACE2 protein of the target cell.
Figure 2 shows the results of analyzing the characteristics of sACE2 exosomes.
Figure 3 shows the results of testing the ability to inhibit COVID-19 SPIKE-sACE2 binding.
Figure 4 shows the neutralizing ability test results of sACE2 exosomes using pseudoviruses with COVID-19 wild-type SPIKE protein and D614G mutant SPIKE beta mutant and delta mutant SPIKE protein.
Figure 5 shows the results of a comparative test of the neutralizing ability of sACE2 exosomes and ACE2 recombinant protein using a pseudovirus with the COVID-19 delta mutant SPIKE protein.
Figure 6 shows a schematic diagram of the Spike Exosome mechanism of action.
Figure 7 shows a schematic diagram of the fusion protein and the results of Spike Exosome characterization.
Figure 8 shows the results of the binding ability experiment between ACE2 protein and Spike exosomes.
Figure 9 shows an overview of the Spike Exosome Immunization experiment.
Figure 10 shows the results of an experiment measuring the concentration of antibodies produced in Spike exosome-inoculated mice and comparing neutralization ability using a pseudovirus containing Spike protein.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples.

Example

I. Exosomes with ACE2 overexpressed on the surface

(1) Development of exosomes with ACE2 overexpressed on the surface

Exosomes are substances with a double lipid membrane structure with a size of 30-100 nm that are secreted from cells. Because it is derived from cells, it has low immunogenicity and has the same membrane topology as cells, so various membrane proteins can be expressed through genetic manipulation. Exosomes typically have membrane proteins such as CD9, CD63, and LAMP2B expressed on their surfaces.

SARS-CoV-2 is a type of coronavirus and like most coronaviruses, it expresses the spike protein. The spike protein binds to the cell surface receptor ACE2, fuses with the cell membrane, and penetrates into the cell through this.

The present invention fuses three genes, wild type soluble ACE2 (sACE2), mutant 1 (V1), and mutant 2 (V2), with the surface marker proteins of exosomes (CD9△TM4), respectively, and sACE2wt on the surface. , sACE2.v1, and sACE2.v2 were developed overexpressed exosomes, respectively. The amino acid sequences of wild-type and mutant sACE2 are shown in the first sequence (sACE2wt), second sequence (sACE2.v1), and third sequence (sACE2.v2) of the sequence list, respectively.

Wild-type and mutant sACE2 were fixed to the surface of exosomes by binding to CD9, the surface marker protein of exosomes. Specifically, in order to fix sACE2 to the cell membrane of exosomes, the fourth transmembrane region of CD9 was deleted (CD9ΔTM4) and then connected to the sACE2 protein. The amino acid sequence of CD9△TM4-sACE2 is shown in sequence 4 (CD9△TM4-sACE2wt), sequence 5 (CD9△TM4-sACE2.v1), and sequence 6 (CD9△TM4-sACE2.v2), respectively. It was. The exosomes isolated using these sequences were named sACE2wt exosome, sACE2.v1 exosome, and sACE2.v2 exosome, respectively, and through this, exosomes with a new structure with sACE2 fixed on the exosome surface were created. Exosomes expressing sACE2 can bind to the SPIKE protein on the surface of SARS-CoV-2, preventing the virus from penetrating into cells through binding to the ACE2 protein of target cells (Figure 1).

To confirm that the present invention works well, a plasmid with eGFP attached was prepared, and the plasmid linked with eGFP-CD9△TM4-sACE2 was transfected into HEK293T cells and cultured to produce cell culture medium. Afterwards, exosomes were separated and purified from the cell culture medium through TFF. To check whether the plasmid was actually expressed within the cell, the expression of GFP was checked using a fluorescence microscope, and it was confirmed that GFP was expressed normally (Figure 2 (a)). CD9△TM4-sACE2wt (sACE2wt exosome), CD9△TM4-sACE2.v1 (sACE2.v1 exosome), CD9△TM4-sACE2.v2 (sACE2.v2 exosome) expressed on the surface of exosomes (sACE2 exosome) The size and number of particles were measured through NTA (nanoparticle tracking analysis) (Figure 2 (B)).

(2) Spike protein-ACE2 protein binding analysis

Through the COVID-19 spike-ACE2 binding assay, the inhibitory ability of spike protein-ACE2 protein binding of sACE2wt exosomes, sACE2v1 exosomes, and sACE2v2 exosomes was evaluated. When incubating SPIKE (SPIKE-Biotin) with biotin attached to a plate coated with ACE2, a system was used in which HRP is fused to streptavidin, which recognizes biotin, and emits light when a substrate is added. When SPIKE-Biotin and exosomes were first incubated at room temperature for 1 hour and then applied to the system, it was confirmed that the binding between ACE2 and SPIKE was inhibited compared to the PBS group or control exosomes.

As a result of the experiment, compared to the group treated with PBS or control exosomes, spike-sACE2 binding was significantly inhibited in the group treated with sACE2v1 exosomes and the group treated with sACE2v2 exosomes, and spike-sACE2 binding was concentration-dependent. was suppressed (see Figure 3; * means P < 0.05).

(3) Neutralization efficacy test of sACE2 exosomes

*In Figure 4, the neutralizing efficacy of sACE2 exosomes was tested using Pseudovirus containing the Spike protein of SARS-CoV-2. Neutralization efficacy was tested using Pseudovirus with WT SPIKE, SPIKE with D614G mutation, SPIKE with Beta mutation K417N, E484K, and N501Y mutations, and Delta mutation SPIKE with L452R, E484K, and D614G mutations. Pseudovirus is a system that uses SPIKE instead of VSV-g, which is used in Lentivirus, using only the surface protein of the Lentivirus skeleton. As a reporter gene, Luciferase is used in the Lentivirus transfer vector, so when Pseudovirus is infected, the degree of infection can be evaluated through the Luciferase system. Pseudovirus and each exosome were first incubated at room temperature, and ACE2-overexpressing HEK293T cells were infected. After 72 hours, the degree of infection was evaluated using Luciferase. When the group containing only pseudoviruses was used as a control group and normalized and displayed, the efficacy of each exosome was confirmed compared to the control exosome HEK293T Exosome. In particular, Pseudovirus with mutant spikes was more effective than Pseudovirus with wild type spikes. It was found that the efficacy of exosomes was higher.

As a result of the experiment, in all mutations, sACE2wt exosomes, sACE2v1 exosomes, and sACE2v2 exosomes showed efficacy in neutralizing pseudoviruses in a concentration-dependent manner (see Figure 4: *: P < 0.05, **: P < 0.01, *** :P<0.001).

Additionally, the neutralization efficacy of sACE2 exosomes and ACE2 recombinant protein was compared using SPIKE with the L452R, E484K, and D614G Delta mutations. As a result of the experiment, when the amount of ACE2 in sACE2wt exosomes was measured through ELISA and compared with the same amount of ACE2 recombinant protein, it was found that the neutralizing effect of exosomes was superior, and it was significantly more effective when delivered through exosomes than the recombinant protein. It was confirmed that it showed excellent efficacy (Figure 5).

II. Development of exosomes with Spike protein overexpressed on the surface

(1) Development of exosomes with Spike protein overexpressed on the surface

Exosomes are substances with a double lipid membrane structure with a size of 30-100 nm that are secreted from cells. Because it is derived from cells, it has the same membrane topology as cells, so various membrane proteins can be expressed through genetic manipulation. Exosomes typically express membrane proteins such as CD9, CD63, and LAMP2B.

SARS-CoV-2 is a type of coronavirus and like most coronaviruses, it expresses the spike protein. The spike protein binds to the cell surface receptor ACE2, fuses with the cell membrane, and penetrates into the cell through this.

In this application, a treatment or vaccine that masks the ACE2 receptor was developed by expressing spike protein on the surface of exosomes. Through genetic manipulation of HEK293T cells, exosome membrane protein Lamp2b-S1 or CD9 1 ^st TM-S1 protein was combined to produce exosomes overexpressed on the surface (Figure 6).

Specifically, to produce exosomes with the Spike protein expressed on the surface, the cDNA of the exosome marker protein and the cDNA of the Spike protein were fused using PCR. To minimize the size, only the S1 unit containing the ACE2 binding domain was used (S2 unit: includes the Transmembrane domain). The amino acid sequence of the S1 unit is shown in sequence 7 of the sequence list.

S1-Lamp2b exosomes have the N-terminus of the S1 unit exposed to the outside, and CD9 ^1st TM-S1 exosomes have the C-terminus of the S1 unit exposed to the outside. S1-Lamp2b complex cDNA was synthesized by linking the S1 unit, which has the receptor binding domain of the spike protein (S Protein) of the SARS-CoV-2 virus, to the N terminus of the exosome marker membrane protein Lamp2b through PCR and DNA ligation methods. CD9 1 ^st TM-S1 complex cDNA was synthesized by linking the first transmembrane domain of the exosome marker membrane protein CD9 to the N terminus of the spike protein (Figure 7 (A)). The amino acid sequences of S1-Lamp2b and CD9 1 ^st TM-S1 are shown as sequence 8 (S1-Lamp2b) and 9 (CD9 1 ^st TM-S1) in the sequence list, respectively.

The particle number and size of the exosomes prepared in this way were analyzed through NTA (Nanoparticle Tracking Analysis). Proteins contained in exosomes were confirmed through Western blot. Exosomes were identified using Alix, an exosome marker protein, and Calnexin, a cell-specific protein. To confirm that Spike protein was overexpressed on the surface of exosomes, the expression of 3xFlag and Lamp2b included in the fusion protein was confirmed using respective antibodies (Figure 7 (B)).

The concentration of S1 protein contained in exosomes was analyzed through ELISA. In the case of CD9 1 ^st TM-S1 exosome, it was confirmed that 200 pg of S1 was contained per 1 ug of exosomal protein, and in the case of S1-Lamp2b exosome, it was confirmed that it contained 100 pg of S1 per 1 ug of exosomal protein ( Figure 7(C)).

*

(2) Spike-ACE2 inhibitor screening analysis

Through Spike-ACE2 inhibitor screening analysis, it was confirmed whether Spike exosomes effectively inhibit the binding between ACE2 and spike protein. Specifically, ACE2 protein was coated on a plate and then reacted with PBS, S1-Lamp2b exosomes, or CD9 ^1st TM-S1 exosomes at room temperature. After removing the used PBS and exosomes, S1-Biotin protein was added to the plate. Afterwards, the S1-Biotin protein bound to the ACE2 protein coated on the plate was detected using Streptavidin-HRP protein. Through luminescence measurement, it was confirmed that the group treated with PBS showed high luminescence, indicating that ACE2-S1-Biotin was bound. As a result of the experiment, when the two types of exosomes were treated at 2.5 ug or 13 ug each, the luminescence was significantly reduced compared to the group treated with PBS, confirming that the two types of exosomes inhibited ACE2-S1-Biotin binding. (See Figure 8: ****: P < 0.0001).

(3) In vivo analysis

To evaluate the efficacy as a vaccine, an experiment was conducted after administering Spike exosomes to mice. To stimulate the immune response, 100 ug of exosomes mixed with an immune enhancer in a 1:1 ratio were administered by subcutaneous injection. In this way, exosomes were administered a total of four times at two-week intervals, and 60 days after the first injection, antibodies were isolated from mouse serum and used in experiments (Figure 9).

The concentration of antibodies produced in mice was measured using ELISA, which can specifically detect S1 protein. As a result of the experiment, it was confirmed that, unlike mice administered PBS, antibodies isolated from mice administered exosomes could be measured by specifically binding to the S1 protein (Figure 10 (A)).

In addition, the neutralizing ability of antibodies produced in mice inoculated with Spike exosomes was tested using a pseudovirus containing the Spike protein. When treated with 5.8 ug and 30 ug of antibodies, it was confirmed that the antibodies of mice administered CD9 1 ^st TM-S1 exosomes significantly reduced pseudovirus infection depending on the concentration (Figure 10 (B) and (C) Reference, *: P < 0.05, ***: P < 0.001).

[Sequence list free text]

1st rank. Amino acid sequence of sACE2wt

SSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDY WRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSL SAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSP YADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK

Second rank. Amino acid sequence of sACE2.v1

SSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNAEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLQVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDY WRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTPGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYLAQPFLLRNGANEGFHEAVGEIMSLSA ATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPY ADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK

Third rank. Amino acid sequence of sACE2.v2

SSSSWLLLSLVAVTAAQSTIEEQAKYFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTTAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDY WRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWEYSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYLAQPFLLRNGANEGFHEAVGEIMSL SAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSP YADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK

4th rank. Amino acid sequence of CD9△TM4-sACE2wt

MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIASATSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTN ITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPS YISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGE IPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK*

Fifth rank. Amino acid sequence of CD9△TM4-sACE2v1

MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIASATSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNAEAEDLFYQSSLASWNYNTNITE ENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLQVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPS YISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTPGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYLAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIP KDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK*

6th rank. Amino acid sequence of CD9△TM4-sACE2.v2

MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIASATSSSSWLLLSLVAVTAAQSTIEEQAKYFLDKFNHEAEDLFYQSSLASWNYNTN ITEENVQNMNNAGDKWSAFLKEQSTTAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPS YISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWEYSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYLAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGE IPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADGSSRGSRADYKDHDGDYKDHDIDYKDDDDK*

7th rank. Amino acid sequence of S1 unit

MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFV FKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVI RGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCPKKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLY QDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARS

8th rank. Amino acid sequence of S1-Lamp2b

MVCFRLFPVPGSGLVLVCLVLGAVRSYAGNSTMGSGGSSFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYS SANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSV LYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTT VRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSELGSGSGSGGSSLELNLTDSENATCLYAKWQMNFTVRYETTNKTYKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIANFTKAASTYSIDSVSFS YNTGDNTTFPDAEDKGILTVDELLAIRIPLNDLFRCNSLSTLEKNDVVQHYWDVLVQAFVQNGTVSTNEFLCDKDKTSTVAPTIHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQLNITQDKVASVININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVNISMYLVNGSVFSIANNNLSYWDAPLGSSYMC EQTVSVSGAFQINTFDLRVQPFNVTQGKYSTAQECSLDDDTILIPIIVGAGLSGLIIVIVIAYVIGRRKSYAGYQTLGSGGSRADYKDHDGDYKDHDIDYKDDDDK*

9th rank. Amino acid sequence of CD9 ^1st TM-S1

MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRFGSGSGSGGSSFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNNK SWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRK RISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNFNGLTGTGVLTESNKKFLPFQQ FGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSSRGSRADYKDHDGDYKDHDIDYKDDDDK*

<110> EXOSTEMTECH CO., LTD. Research and Business Foundation SUNGKYUNKWAN UNIVERSITY <120> Vaccine or pharmaceutical composition for preventing or treating COVID-19 using exosomes <130> P20-254 <160> 9 <170> KoPatentIn 3.0 <210> 1 <211> 644 <212> PRT < 213> Homo sapiens <400> 1 Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala Ala 1 5 10 15 Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn 20 25 30 His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn 35 40 45 Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala 50 55 60 Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln 65 70 75 80 Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu 85 90 95 Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser 100 105 110 Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr 115 120 125 Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu 130 135 140 Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg 145 150 155 160 Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg 165 170 175 Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala 180 185 190 Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val 195 200 205 Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp 210 215 220 Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His 225 230 235 240 Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser 245 250 255 Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg 260 265 270 Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro 275 280 285 Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln 290 295 300 Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro 305 310 315 320 Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly 325 330 335 Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys 340 345 350 Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe 355 360 365 Leu Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr 370 375 380 Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His 385 390 395 400 Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His 405 410 415 Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu 420 425 430 Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr 435 440 445 Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys 450 455 460 Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys 465 470 475 480 Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr 485 490 495 Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile 500 505 510 Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu 515 520 525 Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser 530 535 540 Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly 545 550 555 560 Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys 565 570 575 Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr 580 585 590 Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp 595 600 605 Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg Gly Ser Arg Ala Asp Tyr 610 615 620 Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp 625 630 635 640 Asp Asp Asp Lys <210> 2 <211> 644 <212> PRT <213> Homo sapiens <400 > 2 Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala Ala 1 5 10 15 Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn 20 25 30 Ala Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn 35 40 45 Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala 50 55 60 Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln 65 70 75 80 Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Gln Val Lys Leu Gln Leu 85 90 95 Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser 100 105 110 Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr 115 120 125 Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu 130 135 140 Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg 145 150 155 160 Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg 165 170 175 Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala 180 185 190 Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val 195 200 205 Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp 210 215 220 Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His 225 230 235 240 Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser 245 250 255 Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg 260 265 270 Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro 275 280 285 Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln 290 295 300 Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro 305 310 315 320 Asn Met Thr Pro Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly 325 330 335 Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys 340 345 350 Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe 355 360 365 Leu Thr Ala His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr 370 375 380 Leu Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His 385 390 395 400 Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His 405 410 415 Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu 420 425 430 Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr 435 440 445 Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys 450 455 460 Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys 465 470 475 480 Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr 485 490 495 Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile 500 505 510 Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu 515 520 525 Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser 530 535 540 Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly 545 550 555 560 Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys 565 570 575 Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr 580 585 590 Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp 595 600 605 Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg Gly Ser Arg Ala Asp Tyr 610 615 620 Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp 625 630 635 640 Asp Asp Asp Lys <210> 3 <211> 644 <212> PRT <213> Homo sapiens <400> 3 Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala Ala 1 5 10 15 Gln Ser Thr Ile Glu Glu Gln Ala Lys Tyr Phe Leu Asp Lys Phe Asn 20 25 30 His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn 35 40 45 Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala 50 55 60 Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Thr Ala Gln 65 70 75 80 Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu 85 90 95 Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser 100 105 110 Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr 115 120 125 Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu 130 135 140 Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg 145 150 155 160 Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg 165 170 175 Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala 180 185 190 Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val 195 200 205 Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp 210 215 220 Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His 225 230 235 240 Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser 245 250 255 Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg 260 265 270 Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro 275 280 285 Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln 290 295 300 Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro 305 310 315 320 Asn Met Thr Gln Gly Phe Trp Glu Tyr Ser Met Leu Thr Asp Pro Gly 325 330 335 Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys 340 345 350 Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe 355 360 365 Leu Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr 370 375 380 Leu Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His 385 390 395 400 Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His 405 410 415 Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu 420 425 430 Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr 435 440 445 Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys 450 455 460 Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys 465 470 475 480 Arg Glu Ile Val Gly Val Val Glu Pro Val Pro Val Pro His Asp Glu Thr Tyr 485 490 495 Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile 500 505 510 Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu 515 520 525 Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser 530 535 540 Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly 545 550 555 560 Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys 565 570 575 Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr 580 585 590 Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp 595 600 605 Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg Gly Ser Arg Ala Asp Tyr 610 615 620 Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp 625 630 635 640 Asp Asp Asp Lys <210> 4 <211> 794 <212> PRT <213> Artificial Sequence <220> <223> CD9(deleteTM4)-sACE2wt <400 > 4 Met Pro Val Lys Gly Gly Thr Lys Cys Ile Lys Tyr Leu Leu Phe Gly 1 5 10 15 Phe Asn Phe Ile Phe Trp Leu Ala Gly Ile Ala Val Leu Ala Ile Gly 20 25 30 Leu Trp Leu Arg Phe Asp Ser Gln Thr Lys Ser Ile Phe Glu Gln Glu 35 40 45 Thr Asn Asn Asn Asn Ser Ser Phe Tyr Thr Gly Val Tyr Ile Leu Ile 50 55 60 Gly Ala Gly Ala Leu Met Met Leu Val Gly Phe Leu Gly Cys Cys Gly 65 70 75 80 Ala Val Gln Glu Ser Gln Cys Met Leu Gly Leu Phe Phe Gly Phe Leu 85 90 95 Leu Val Ile Phe Ala Ile Glu Ile Ala Ala Ala Ile Trp Gly Tyr Ser 100 105 110 His Lys Asp Glu Val Ile Lys Glu Val Gln Glu Phe Tyr Lys Asp Thr 115 120 125 Tyr Asn Lys Leu Lys Thr Lys Asp Glu Pro Gln Arg Glu Thr Leu Lys 130 135 140 Ala Ile Ala Ser Ala Thr Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu 145 150 155 160 Val Ala Val Thr Ala Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr 165 170 175 Phe Leu Asp Lys Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser 180 185 190 Ser Leu Ala Ser Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val 195 200 205 Gln Asn Met Asn Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu 210 215 220 Gln Ser Thr Leu Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu 225 230 235 240 Thr Val Lys Leu Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val 245 250 255 Leu Ser Glu Asp Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met 260 265 270 Ser Thr Ile Tyr Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln 275 280 285 Glu Cys Leu Leu Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser 290 295 300 Leu Asp Tyr Asn Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu 305 310 315 320 Val Gly Lys Gln Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys 325 330 335 Asn Glu Met Ala Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp 340 345 350 Arg Gly Asp Tyr Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg 355 360 365 Gly Gln Leu Ile Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro 370 375 380 Leu Tyr Glu His Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala 385 390 395 400 Tyr Pro Ser Tyr Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu 405 410 415 Gly Asp Met Trp Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val 420 425 430 Pro Phe Gly Gln Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp 435 440 445 Gln Ala Trp Asp Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe 450 455 460 Val Ser Val Gly Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser 465 470 475 480 Met Leu Thr Asp Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr 485 490 495 Ala Trp Asp Leu Gly Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys 500 505 510 Val Thr Met Asp Asp Phe Leu Thr Ala His His Glu Met Gly His Ile 515 520 525 Gln Tyr Asp Met Ala Tyr Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly 530 535 540 Ala Asn Glu Gly Phe His Glu Ala Val Gly Glu Ile Met Ser Leu Ser 545 550 555 560 Ala Ala Thr Pro Lys His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp 565 570 575 Phe Gln Glu Asp Asn Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala 580 585 590 Leu Thr Ile Val Gly Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp 595 600 605 Arg Trp Met Val Phe Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys 610 615 620 Lys Trp Trp Glu Met Lys Arg Glu Ile Val Gly Val Val Glu Pro Val 625 630 635 640 Pro His Asp Glu Thr Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser 645 650 655 Asn Asp Tyr Ser Phe Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe 660 665 670 Gln Phe Gln Glu Ala Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu 675 680 685 His Lys Cys Asp Ile Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe 690 695 700 Asn Met Leu Arg Leu Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu 705 710 715 720 Asn Val Val Gly Ala Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr 725 730 735 Phe Glu Pro Leu Phe Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe 740 745 750 Val Gly Trp Ser Thr Asp Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg 755 760 765 Gly Ser Arg Ala Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His 770 775 780 Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys 785 790 <210> 5 <211> 794 <212> PRT <213> Artificial Sequence <220> <223> CD9(deleteTM4)-sACE2v1 <400> 5 Met Pro Val Lys Gly Gly Thr Lys Cys Ile Lys Tyr Leu Leu Phe Gly 1 5 10 15 Phe Asn Phe Ile Phe Trp Leu Ala Gly Ile Ala Val Leu Ala Ile Gly 20 25 30 Leu Trp Leu Arg Phe Asp Ser Gln Thr Lys Ser Ile Phe Glu Gln Glu 35 40 45 Thr Asn Asn Asn Asn Ser Ser Phe Tyr Thr Gly Val Tyr Ile Leu Ile 50 55 60 Gly Ala Gly Ala Leu Met Met Leu Val Gly Phe Leu Gly Cys Cys Gly 65 70 75 80 Ala Val Gln Glu Ser Gln Cys Met Leu Gly Leu Phe Phe Gly Phe Leu 85 90 95 Leu Val Ile Phe Ala Ile Glu Ile Ala Ala Ala Ile Trp Gly Tyr Ser 100 105 110 His Lys Asp Glu Val Ile Lys Glu Val Gln Glu Phe Tyr Lys Asp Thr 115 120 125 Tyr Asn Lys Leu Lys Thr Lys Asp Glu Pro Gln Arg Glu Thr Leu Lys 130 135 140 Ala Ile Ala Ser Ala Thr Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu 145 150 155 160 Val Ala Val Thr Ala Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr 165 170 175 Phe Leu Asp Lys Phe Asn Ala Glu Ala Glu Asp Leu Phe Tyr Gln Ser 180 185 190 Ser Leu Ala Ser Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val 195 200 205 Gln Asn Met Asn Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu 210 215 220 Gln Ser Thr Leu Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu 225 230 235 240 Gln Val Lys Leu Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val 245 250 255 Leu Ser Glu Asp Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met 260 265 270 Ser Thr Ile Tyr Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln 275 280 285 Glu Cys Leu Leu Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser 290 295 300 Leu Asp Tyr Asn Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu 305 310 315 320 Val Gly Lys Gln Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys 325 330 335 Asn Glu Met Ala Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp 340 345 350 Arg Gly Asp Tyr Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg 355 360 365 Gly Gln Leu Ile Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro 370 375 380 Leu Tyr Glu His Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala 385 390 395 400 Tyr Pro Ser Tyr Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu 405 410 415 Gly Asp Met Trp Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val 420 425 430 Pro Phe Gly Gln Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp 435 440 445 Gln Ala Trp Asp Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe 450 455 460 Val Ser Val Gly Leu Pro Asn Met Thr Pro Gly Phe Trp Glu Asn Ser 465 470 475 480 Met Leu Thr Asp Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr 485 490 495 Ala Trp Asp Leu Gly Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys 500 505 510 Val Thr Met Asp Asp Phe Leu Thr Ala His His Glu Met Gly His Ile 515 520 525 Gln Tyr Asp Met Ala Tyr Leu Ala Gln Pro Phe Leu Leu Arg Asn Gly 530 535 540 Ala Asn Glu Gly Phe His Glu Ala Val Gly Glu Ile Met Ser Leu Ser 545 550 555 560 Ala Ala Thr Pro Lys His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp 565 570 575 Phe Gln Glu Asp Asn Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala 580 585 590 Leu Thr Ile Val Gly Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp 595 600 605 Arg Trp Met Val Phe Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys 610 615 620 Lys Trp Trp Glu Met Lys Arg Glu Ile Val Gly Val Val Glu Pro Val 625 630 635 640 Pro His Asp Glu Thr Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser 645 650 655 Asn Asp Tyr Ser Phe Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe 660 665 670 Gln Phe Gln Glu Ala Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu 675 680 685 His Lys Cys Asp Ile Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe 690 695 700 Asn Met Leu Arg Leu Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu 705 710 715 720 Asn Val Val Gly Ala Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr 725 730 735 Phe Glu Pro Leu Phe Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe 740 745 750 Val Gly Trp Ser Thr Asp Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg 755 760 765 Gly Ser Arg Ala Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His 770 775 780 Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys 785 790 <210> 6 <211> 794 <212> PRT <213> Artificial Sequence <220> <223> CD9(deleteTM4)-sACE2.v2 <400> 6 Met Pro Val Lys Gly Gly Thr Lys Cys Ile Lys Tyr Leu Leu Phe Gly 1 5 10 15 Phe Asn Phe Ile Phe Trp Leu Ala Gly Ile Ala Val Leu Ala Ile Gly 20 25 30 Leu Trp Leu Arg Phe Asp Ser Gln Thr Lys Ser Ile Phe Glu Gln Glu 35 40 45 Thr Asn Asn Asn Asn Ser Ser Phe Tyr Thr Gly Val Tyr Ile Leu Ile 50 55 60 Gly Ala Gly Ala Leu Met Met Leu Val Gly Phe Leu Gly Cys Cys Gly 65 70 75 80 Ala Val Gln Glu Ser Gln Cys Met Leu Gly Leu Phe Phe Gly Phe Leu 85 90 95 Leu Val Ile Phe Ala Ile Glu Ile Ala Ala Ala Ile Trp Gly Tyr Ser 100 105 110 His Lys Asp Glu Val Ile Lys Glu Val Gln Glu Phe Tyr Lys Asp Thr 115 120 125 Tyr Asn Lys Leu Lys Thr Lys Asp Glu Pro Gln Arg Glu Thr Leu Lys 130 135 140 Ala Ile Ala Ser Ala Thr Ser Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu 145 150 155 160 Val Ala Val Thr Ala Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Tyr 165 170 175 Phe Leu Asp Lys Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser 180 185 190 Ser Leu Ala Ser Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val 195 200 205 Gln Asn Met Asn Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu 210 215 220 Gln Ser Thr Thr Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu 225 230 235 240 Thr Val Lys Leu Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val 245 250 255 Leu Ser Glu Asp Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met 260 265 270 Ser Thr Ile Tyr Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln 275 280 285 Glu Cys Leu Leu Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser 290 295 300 Leu Asp Tyr Asn Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu 305 310 315 320 Val Gly Lys Gln Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys 325 330 335 Asn Glu Met Ala Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp 340 345 350 Arg Gly Asp Tyr Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg 355 360 365 Gly Gln Leu Ile Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro 370 375 380 Leu Tyr Glu His Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala 385 390 395 400 Tyr Pro Ser Tyr Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu 405 410 415 Gly Asp Met Trp Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val 420 425 430 Pro Phe Gly Gln Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp 435 440 445 Gln Ala Trp Asp Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe 450 455 460 Val Ser Val Gly Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Tyr Ser 465 470 475 480 Met Leu Thr Asp Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr 485 490 495 Ala Trp Asp Leu Gly Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys 500 505 510 Val Thr Met Asp Asp Phe Leu Thr Ala His His Glu Met Gly His Ile 515 520 525 Gln Tyr Asp Met Ala Tyr Leu Ala Gln Pro Phe Leu Leu Arg Asn Gly 530 535 540 Ala Asn Glu Gly Phe His Glu Ala Val Gly Glu Ile Met Ser Leu Ser 545 550 555 560 Ala Ala Thr Pro Lys His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp 565 570 575 Phe Gln Glu Asp Asn Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala 580 585 590 Leu Thr Ile Val Gly Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp 595 600 605 Arg Trp Met Val Phe Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys 610 615 620 Lys Trp Trp Glu Met Lys Arg Glu Ile Val Gly Val Val Glu Pro Val 625 630 635 640 Pro His Asp Glu Thr Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser 645 650 655 Asn Asp Tyr Ser Phe Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe 660 665 670 Gln Phe Gln Glu Ala Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu 675 680 685 His Lys Cys Asp Ile Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe 690 695 700 Asn Met Leu Arg Leu Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu 705 710 715 720 Asn Val Val Gly Ala Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr 725 730 735 Phe Glu Pro Leu Phe Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe 740 745 750 Val Gly Trp Ser Thr Asp Trp Ser Pro Tyr Ala Asp Gly Ser Ser Arg 755 760 765 Gly Ser Arg Ala Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His 770 775 780 Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys 785 790 <210> 7 <211> 686 <212> PRT <213> Unknown <220> <223> SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) <400> 7 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 675 680 685 <210> 8 <211> 1147 <212> PRT <213 > Artificial Sequence <220> <223> S1-Lamp2b <400> 8 Met Val Cys Phe Arg Leu Phe Pro Val Pro Gly Ser Gly Leu Val Leu 1 5 10 15 Val Cys Leu Val Leu Gly Ala Val Arg Ser Tyr Ala Gly Asn Ser Thr 20 25 30 Met Gly Ser Gly Gly Ser Ser Phe Val Phe Leu Val Leu Leu Pro Leu 35 40 45 Val Ser Ser Gln Cys Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro 50 55 60 Ala Tyr Thr Asn Ser Phe Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val 65 70 75 80 Phe Arg Ser Ser Val Leu His Ser Thr Gln Asp Leu Phe Leu Pro Phe 85 90 95 Phe Ser Asn Val Thr Trp Phe His Ala Ile His Val Ser Gly Thr Asn 100 105 110 Gly Thr Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly Val 115 120 125 Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe 130 135 140 Gly Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn Asn 145 150 155 160 Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn Asp 165 170 175 Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met Glu 180 185 190 Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr 195 200 205 Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe 210 215 220 Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys 225 230 235 240 Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln 245 250 255 Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn 260 265 270 Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr 275 280 285 Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr 290 295 300 Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn 305 310 315 320 Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu 325 330 335 Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln 340 345 350 Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro 355 360 365 Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg 370 375 380 Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val 385 390 395 400 Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys 405 410 415 Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn 420 425 430 Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile 435 440 445 Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro 450 455 460 Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp 465 470 475 480 Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys 485 490 495 Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln 500 505 510 Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe 515 520 525 Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 530 535 540 Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala 545 550 555 560 Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys 565 570 575 Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu 580 585 590 Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala 595 600 605 Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp 610 615 620 Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr 625 630 635 640 Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys Thr 645 650 655 Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg 660 665 670 Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu 675 680 685 Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile 690 695 700 Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg 705 710 715 720 Arg Ala Arg Ser Glu Leu Gly Ser Gly Ser Gly Ser Gly Gly Ser Ser 725 730 735 Leu Glu Leu Asn Leu Thr Asp Ser Glu Asn Ala Thr Cys Leu Tyr Ala 740 745 750 Lys Trp Gln Met Asn Phe Thr Val Arg Tyr Glu Thr Thr Asn Lys Thr 755 760 765 Tyr Lys Thr Val Thr Ile Ser Asp His Gly Thr Val Thr Tyr Asn Gly 770 775 780 Ser Ile Cys Gly Asp Asp Gln Asn Gly Pro Lys Ile Ala Val Gln Phe 785 790 795 800 Gly Pro Gly Phe Ser Trp Ile Ala Asn Phe Thr Lys Ala Ala Ser Thr 805 810 815 Tyr Ser Ile Asp Ser Val Ser Phe Ser Tyr Asn Thr Gly Asp Asn Thr 820 825 830 Thr Phe Pro Asp Ala Glu Asp Lys Gly Ile Leu Thr Val Asp Glu Leu 835 840 845 Leu Ala Ile Arg Ile Pro Leu Asn Asp Leu Phe Arg Cys Asn Ser Leu 850 855 860 Ser Thr Leu Glu Lys Asn Asp Val Val Gln His Tyr Trp Asp Val Leu 865 870 875 880 Val Gln Ala Phe Val Gln Asn Gly Thr Val Ser Thr Asn Glu Phe Leu 885 890 895 Cys Asp Lys Asp Lys Thr Ser Thr Val Ala Pro Thr Ile His Thr Thr 900 905 910 Val Pro Ser Pro Thr Thr Thr Pro Thr Pro Lys Glu Lys Pro Glu Ala 915 920 925 Gly Thr Tyr Ser Val Asn Asn Gly Asn Asp Thr Cys Leu Leu Ala Thr 930 935 940 Met Gly Leu Gln Leu Asn Ile Thr Gln Asp Lys Val Ala Ser Val Ile 945 950 955 960 Asn Ile Asn Pro Asn Thr His Ser Thr Gly Ser Cys Arg Ser His 965 970 975 Thr Ala Leu Leu Arg Leu Asn Ser Ser Thr Ile Lys Tyr Leu Asp Phe 980 985 990 Val Phe Ala Val Lys Asn Glu Asn Arg Phe Tyr Leu Lys Glu Val Asn 995 1000 1005 Ile Ser Met Tyr Leu Val Asn Gly Ser Val Phe Ser Ile Ala Asn Asn 1010 1015 1020 Asn Leu Ser Tyr Trp Asp Ala Pro Leu Gly Ser Ser Tyr Met Cys Asn 1025 1030 1035 1040 Lys Glu Gln Thr Val Ser Val Ser Gly Ala Phe Gln Ile Asn Thr Phe 1045 1050 1055 Asp Leu Arg Val Gln Pro Phe Asn Val Thr Gln Gly Lys Tyr Ser Thr 1060 1065 1070 Ala Gln Glu Cys Ser Leu Asp Asp Asp Thr Ile Leu Ile Pro Ile Ile 1075 1080 1085 Val Gly Ala Gly Leu Ser Gly Leu Ile Ile Val Ile Val Ile Ala Tyr 1090 1095 1100 Val Ile Gly Arg Arg Lys Ser Tyr Ala Gly Tyr Gln Thr Leu Gly Ser 1105 1110 1115 1120 Gly Gly Ser Arg Ala Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp 1125 1130 1135 His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys 1140 1145 <210> 9 <211> 760 <212> PRT <213> Artificial Sequence <220> <223> CD9 1st TM-S1 <400> 9 Met Pro Val Lys Gly Gly Thr Lys Cys Ile Lys Tyr Leu Leu Phe Gly 1 5 10 15 Phe Asn Phe Ile Phe Trp Leu Ala Gly Ile Ala Val Leu Ala Ile Gly 20 25 30 Leu Trp Leu Arg Phe Gly Ser Gly Ser Gly Ser Gly Gly Ser Ser Phe 35 40 45 Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val Asn Leu 50 55 60 Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe Thr Arg 65 70 75 80 Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu His Ser 85 90 95 Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp Phe His 100 105 110 Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro 115 120 125 Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser 130 135 140 Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr 145 150 155 160 Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val 165 170 175 Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr Tyr His 180 185 190 Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser 195 200 205 Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp 210 215 220 Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe 225 230 235 240 Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile 245 250 255 Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu 260 265 270 Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu 275 280 285 Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp 290 295 300 Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr 305 310 315 320 Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp 325 330 335 Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe 340 345 350 Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro 355 360 365 Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe 370 375 380 Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn 385 390 395 400 Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn 405 410 415 Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys 420 425 430 Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile 435 440 445 Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile 450 455 460 Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile 465 470 475 480 Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn 485 490 495 Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg 500 505 510 Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly 515 520 525 Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 530 535 540 Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser 545 550 555 560 Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser 565 570 575 Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu 580 585 590 Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe 595 600 605 Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp 610 615 620 Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly 625 630 635 640 Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val 645 650 655 Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala 660 665 670 Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val 675 680 685 Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn 690 695 700 Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr 705 710 715 720 Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Ser Arg Gly Ser 725 730 735 Arg Ala Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile 740 745 750Asp Tyr Lys Asp Asp Asp Asp Lys 755 760

Claims (7)

An ACE2 (angiotensin-converting enzyme 2) protein or a fusion protein containing it is expressed on the surface, and the ACE2 protein or a fusion protein containing it is an amino acid sequence selected from the group consisting of sequences 2 to 6 in the sequence list. Consisting of recombinant exosomes. A recombinant vector comprising a nucleic acid sequence encoding one or more amino acid sequences selected from the group consisting of sequences 2 to 6 of the sequence list. Isolated cells transformed with the recombinant vector of claim 2. Culturing the separated cells of claim 3; and
Comprising the step of isolating and purifying recombinant exosomes from the cell culture medium,
Method for producing recombinant exosomes for use as an active ingredient in a vaccine or therapeutic composition for coronavirus infection. A pharmaceutical composition for treating respiratory diseases caused by coronavirus infection, comprising the recombinant exosome according to claim 1 as an active ingredient. The pharmaceutical composition according to claim 5, wherein the respiratory disease caused by the coronavirus infection is coronavirus disease 2019 (COVID-19). The pharmaceutical composition according to claim 5, wherein the exosome has a coronavirus neutralizing effect.