IL158109A - Replikin peptides and uses thereof - Google Patents

Description

ΙΙίΙΙΙΡΙΙΪιΪ 158109 p-n I 453359 τηκ Replikin peptue, and uses thereof Samuel BOGOCH Eknore S. BOGOCH REPLIKI PEPTIDES AND USES THEREOF CROSS REFERENCE TO OTHER APPLICATIONS

[001] This application is a Continuation-In-Part of Application Nos. US 09/984,056 and US 09/984,057, both filed October 26, 2001, which claim priority from Provisional Applications 60/303,396, filed July 9, 2001 and 60/278,761 filed March 27, 2001, the subject matter of which is incorporated herein by reference.

FIELD OF THE INVENTION

[002] This invention relates to the identification and use of Replikins, a class of peptides that share structural characteristics. In particular, this invention relates to Replikins which have been identified in influenza viruses and their use in designing influenza virus vaccines. The invention also relates to Replikins which have been identified in Bacillus anthracis and Small Pox Virus (Variola).

BACKGROUND OF THE INVENTION

[003] Influenza is an acute respiratory illness of global importance. Despite international attempts to control influenza virus outbreaks through vaccination influenza infections remain an important cause of morbidity and mortality.

Worldwide influenza pandemics have occurred at irregular and previously unpredictable intervals throughout history and it is expected that they will continue to occur in the future. The impact of pandemic influenza is substantial in terms of morbidity, mortality and economic cost.

[004] Influenza vaccines remain the most effective defense against influenza virus, but because of the ability of the virus to mutate and the availability of non-human host reservoirs it is expected that influenza will remain an emergent or re-emergent infection. Global influenza surveillance indicates that influenza viruses may vary within a country and between countries and continents during an influenza season. Virologic surveillance is of importance in monitoring antigenic shift and drift.

Disease surveillance is also important in assessing the impact of epidemics. Both types of information have provided the basis of vaccine composition and the correct use of antivirals. However, to date there has been only annual post hoc hematological classification of the increasing number of emerging influenza virus strains, and no specific chemical structure of the viruses has been identified as an indicator of approaching influenza epidemic or pandemic. Currently, the only basis for annual classification of influenza virus as active, inactive or prevalent in a given year is the activities of the virus hemagglutinin and neuraminidase proteins. No influenza viral chemical structure has been identified that can be used for quantitative warning of epidemics or pandemics or to design more effective and safer vaccines.

[005] Because of the annual administration of influenza vaccines and the short period of time when a vaccine can be administered, strategies directed at improving vaccine coverage are of critical importance.

[006] Another disease which has proved difficult to treat and for which there is no effective vaccine is malaria. Malaria causes much physical and economic hardship in tropical regions. Malaria is caused by Plasmodium falciparum, which has proved to be extremely resistant to treatment and to date, a vaccine for malaria remains elusive. Thus, there is a need for effective malaria vaccines and methods of treating or preventing the disease.

Other diseases for which an effective vaccine is needed include anthrax and small pox. However, to date, no vaccine has been effective for prevention of disease caused by these pathological organisms. Thus, there is a need for vaccines for these pathogens, as well as a need for effective strategies for formulating vaccines to various pathogens. [006A] Israel Patent No. 141775, of the same Applicant, relates to an isolated peptide, a purified antibody which specifically recognizes the same, a therapeutic composition comprising the same, a method of diagnosing and a kit comprising the same.

SUMMARY OF THE INVENTION

[007] In one aspect of the invention there are provided isolated influenza virus peptides containing a Replikin sequence. The influenza virus peptides comprise from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten amino acid residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues.

[008] In another aspect of the invention there is provided a process for stimulating the immune system of a subject to produce antibodies that bind specifically to an influenza virus Replikin sequence, said process comprising administering to the subject an effective amount of a dosage of a composition comprising at least one influenza virus replikin peptide. In a preferred embodiment the composition comprises at least one peptide that is present in an emerging strain of influenza virus.

[009] The present invention also provides antibodies that bind specifically to an influenza virus Replikin, as defined herein, as well as antibody cocktails containing a plurality of antibodies that specifically bind to influenza virus Replikins. In one embodiment of the invention, there are provided compositions comprising an antibody or antibodies that specifically bind to an influenza Replica and a pharmaceutically acceptable carrier.

[010] The present invention also provides therapeutic compositions comprising one or more of isolated influenza virus peptides having from 7 to about 50 amino acids comprising 1) at least one lysine residue located six to ten residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues, and a pharmaceutically acceptable carrier.

[011] In another aspect of the invention there is provided an antisense nucleic acid molecule complementary to an influenza virus hemagglutinin Replikin rnRNA sequence, said Replikin mRNA sequence having from 7 to about 50 amino acids comprising (1) at least one lysine residue located six to ten residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues.

[012] In yet another aspect of the invention, there is provided a method of stimulating the immune system of a subject to produce antibodies to influenza virus comprising administering an effective amount of at least one influenza virus R^likin peptide having from 7 to about 50 amino acids comprising (1) at least one lysine residue located six to ten amino acid residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues.

[013] In another aspect, there is provided a method of selecting an influenza virus peptide for inclusion in an influenza virus vaccine comprising (1) obtaining at least one isolate of each strain of a plurahty of strains of influenza virus, (2) analyzing the hemagglutinin amino acid sequence of the at least one isolate of each strain of the plurahty of strains of influenza virus for the presence and concentration of Replikin sequences, (3) comparing the concentration of Replikin sequences in the hemagglutinin amino acid sequence of the at least one isolate of each strain of the plurahty of strains of influenza virus to the concentration of Replikin sequences observed in the hemagglutinin amino acid sequence of each of the strains at least one earlier time period to provide the concentration of Repli ns for at least two time periods, said at least one earlier time period being within about six months to about three years prior to step (1), (4) identifying the strain of influenza virus having the highest increase in concentration of Replikin sequences during the at least two time periods, (5) selecting at least one Replikin sequence present in the strain of influenza virus peptide identified in step (4) as a peptide for inclusion in an influenza virus vaccine.

[014] The present invention also provides a method of making an influenza virus vaccine comprising (1) identifying a strain of influenza virus as an emerging strain, (2) selecting at least one Replikin sequence present in the emerging strain as a peptide template for influenza virus vaccine manufacture, (3) synthesizing peptides having the amino acid sequence of the at least one Replikin sequence selected in step (2), and (4) combining a therapeutically effective amount of the peptides of step (4) with a pharmaceutically acceptable carrier and/or adjuvant.

[015] In another aspect, the invention is directed to a method of identifying an emerging strain of influenza virus for diagnostic or therapeutic purposes comprising (1) obtaining at least one isolate of each strain of a plurahty of strains of influenza virus, (2) analyzing the hemagglutinin amino acid sequence of the at least one isolate of each strain of the plurality of strains of influenza virus for the presence and concentration of Replikin sequences, (3) comparing the concentration of Replikin sequences in the hemagglutinin amino acid sequence of the at least one isolate of each strain of the plurality of strains of influenza virus to the concentration of Replikin sequences observed in the hemagglutinin amino acid sequence of each of the strains at at least one earlier time period to provide the concentration of Repli ns for at least two time periods, said at least one earlier time period being within about six months to about three years prior to step (1), and (4) identifying the strain of influenza virus having the highest increase in concentration of Replikin sequences during the at least two time periods.

[016] In yet another aspect of the invention, there is provided an influenza virus vaccine comprising at least one isolated Replikin present in the hemagglutinin protein of an emerging strain of influenza virus and a pharmaceutically acceptable carrier and/or adjuvant.

[017] Also provided by the present invention is a method of preventing or treating influenza virus infection comprising adnu stering to a patient in need thereof a vaccine comprising at least one isolated Replikin present in the hemagglutinin protein of an emerging strain of influenza virus and a pharmaceutically acceptable carrier and/or adjuvant.

[018] In another aspect of the invention, there are provided vaccines and methods for preventing or treating malaria. The malaria vaccines comprise at least one isolated Plasmodium falciparum Replikin. The present invention also provides methods for treating or preventing malaria comprising admmistering to a patient an effective amount of a vaccine comprising at least one isolated Plasmodium falciparum Replikin.

[019] Also provided by the present invention are antibodies, antibody cocktails and compositions that comprise antibodies that specifically bind to a Replikin or Replikms present in a malaria antigen of Plasmodium falciparum.

In another aspect of the invention there are provided isolated Bacillus anthracis (Anthrax) peptides containing a replikin sequence. The Anthrax peptides comprise from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten amino acid residues from a second lysine residue; (2) at least one histidine residue; and (3) at least lysine residues. In another embodiment of this aspect of the invention there are provided Small Pox Virus peptides contauiing a replikin sequence which comprises from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten ainino acid residues from a second lysine residue; (2) at least one Mstidine residue; and (3) at least 6% lysine residues.

In another aspect of the invention there is provided a process for stimulating the immune system of a subject to produce antibodies that bind specifically to Anthrax polypeptides containing a replikin sequence, said process comprising acmiinistering to the subject an effective amount of a dosage of a composition comprising at least one Anthrax replikin peptide. In a preferred embodiment the composition comprises at least one peptide selected from SEQ ID NO. 91, SEQ ID NO. 92, SEQ ID NO. 93, SEQ ID NO. 94, SEQ ID NO. 95, SEQ ID NO. 96, SEQ ID NO. 79, SEQ ID NO. 98 or a combination thereof.

In another embodiment of this aspect of the invention there is provided a process for stimulating the immune system of a subject to produce antibodies that bind specifically to Small Pox Virus polypeptides containing a replikin sequence, said process comprising administering to the subject an effective amount of a dosage of a composition comprising at least one Small Pox Virus rephkm peptide. Bi a preferred embodiment the composition comprises a peptide selected from SEQ ID NO. 99, SEQ ID NO. 100, SEQ ID NO. 101, SEQ ID NO. 102, SEQ ID NO. 103, or a combination thereof.

In another aspect of the invention there are provided antisense nucleic acid molecules complementary to the coding strand of the gene or to th e mRNA encoding the Bacillus anthracis Anthrax Lethal Factor Protein pXOl-107 peptide, wherein said antisense nucleic acid molecule is complementary to a nucleotide sequence encoding the peptide of SEQ ID NO. 91, SEQ ID NO. 92, SEQ ID NO. 93, SEQ ID NO. 94, SEQ ID NO. 95, SEQ ID NO. 96, SEQ ID NO. 97, SEQ ID NO. 98.

There are also provided antisense nucleic acid molecule complementary to the coding strand of the gene or to the mRNA encoding the Small Pox Virus Surface Antigen S Precursor Protein, wherein said antisense nucleic acid molecule is complementary to a nucleotide sequence encoding the peptide of SEQ ID NO. 99, SEQ ID NO. 100, SEQ ID NO. 101, SEQ ID NO. 102, or SEQ ID NO. 103.

The present invention also provides methods for detecting the presence of a contaminating organism in a body sample or environmental sample comprising 1) isolating nucleic acids from the body sample or environmental sample; 2) screening the nucleic acids for the presence of a replikin structure; and 3) correlating the presence of a Replikin structure with the presence of the contaminating organism.

In yet another aspect of the invention there is provided a method for increasing the replication rate of an organism comprising transforming a gene encoding an enzyme having a replication function in the organism with at least one Replikin structure.

[020] As used herein, the term "peptide" refers to a compound of two or more amino acids in which the carboxyl group of one is united with an amino group of another, forming a peptide bond. The term peptide is also used to denote the amino acid sequence encoding such a compound. Thus, a peptide sequence may be a subsequence of a larger polypeptide sequence. As used herein, a Replikin peptide is a peptide having 7 to about 50 amino acids comprising (1) at least one lysine residue located six to ten amino acid residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues. Similarly, a replikin sequence is the amino acid sequence encoding such a peptide.

[021] The phrase "emerging strain" as used herein refers to a strain of influenza virus identified as having an increasing concentration of Replikin sequences in its hemagglutinin and/or neuraminidase protein sequence, relative to the concentration of replikins in other strains of influenza virus. The increase in concentration occurs over a period of at least about six months, and preferably over a period of at least about one year, most preferably over a period of at least about three years or more .

BRIEF DESCRIPTION OF THE DRAWINGS

[022] Figure 1 is a bar graph depicting the frequency of occurrence of replikins in various protein groups.

[023] Figure 2 is a graph depicting the percentage of malignin per milligram total membrane protein during anaerobic replication of glioblastoma cells.

[024] Figure 3 is a bar graph showing amount of antimalignin antibody produced in response to exposure to the recognin 16-men

[025] Figure 4A is a photograph of a blood smear taken with ordinary and fluorescent light. Figure 4B is a photograph of a blood smear taken with ordinary and fluorescent light illustrating the presence of two leukemic cells. Figure 4C is a photograph of a dense layer of glioma cells in the presence of antimalignin antibody. Figure 4D and Figure 4E are photographs of the layer of cells in Figure 4C taken at 10 30 and 45 minutes following addition of antimalignin antibody.

[026] Figure 4F is a bar graph showing the inhibition of growth of small cell lung carcinoma cells in vitro by antimalignin antibody.

[027] Figure 5 is a plot of the amount of antimalignin antibody present in the serum of patients with benign or malignant breast disease pre-and post surgery.

[028] Figure 6 is a box diagram depicting an embodiment of the invention wherein a computer is used to carry out the 3- point-recognition method of identifying replikin sequences.

[029] Figure 7 is a graph showing the concentration of Replikins observed in hemagglutinin of influenza B and influenza A strain, H1N1, on a year by year basis 20 from 1918 through 2001.

[030] Figure 8 is a graph of the replikin concentration observed in hemagglutinin of influenza A strains, H2N2 and H3N2, as well as an emerging strain defined by its constituent Replikins, designated H3N2(R), on a year by year basis from 1950 to 2001. [030A] Passages of the description which are outside the scope of the claims do not constitute part of the claimed invention.

DETAILED DESCRIPTION OF THE INVENTION

[031] The present invention provides methods for predicting future epidemics or 30 pandemics of influenza virus, and vaccines and methods of designing effective vaccines against influenza virus. Identification of a new family of small peptides related to the phenomenon of rapid replication, referred to herein as Replikins, provides new targets for detection of pathogens in a sample and vaccine development, such as for example, influenza virus detection and influenza vaccine development Identification of this new family of peptides also provides for the detection of malaria and provides new targets for malaria vaccine development. The discovery of this family of peptides also provides for the detection and provides new targets for anthrax and small pox virus, for example. In general, knowledge of and identification of this family of peptides enables development of effective vaccines for any organism that harbors Replikins.

[032] The first Replikin sequence to be identified was the cancer cell Replikin found in a brain cancer protein, malignin, which was demonstrated to be enriched ten-fold during rapid anaerobic replication of glioblastoma multiforme (glioma) cells. (Figure 2) Malignin is a lOKDa portion of the 250 Da glycoprotein 10B, which was isolated in vivo and in vitro from membranes of glioblastoma multiforme (glioma) cells. Hydrolysis and mass spectroscopy of maHgnin revealed al6-mer peptide sequence, ykagvaflhkkndide (SEQ Π) NO.:4), which is referred to herein as the glioma Replikin and which includes the shorter peptide, kagvafihkk (SEQ ID NO.: 1), both of which apparently are absent in the normal human genome.

[033] Table 1 illustrates how the sequence of the glioma Replikin, the 16-mer peptide sequence, ykagvaflhkkndide (SEQ ID NO.: 4) was determined.

Table 1 16-mer peptide sequence ykagvaflhkkndide obtained from malignin by hydrolysis and mass spectrometry

[034] When the 16-mer glioma Replikin was synthesized and injected as a synthetic vaccine into rabbits, abundant antimahgnin antibody was produced. (Bogoch et al., Cancer Detection and Prevention, 26(Supp. 1): 402 (2002). The concentration of antimalignin antibody in serum in vivo has been shown to relate quantitatively to the survival of cancer patients. (Bogoch et al., Protides of Biological Fluids, 31 :739-747 (1984). In vitro antimahgnin antibodies have been shown to be cytotoxic to cancer cells at a concentration of picograms (femtomolar) per cancer cell. (Bogoch et al., Cancer Detection and Prevention, 26(Supp. 1): 402 (2002).

[035] Studies carried out by the inventors showed that the glioma Replikin is not represented in the normal healthy human genome. Consequently, a search for the origin and possible homologues of the Replikin sequence was undertaken by analysis of published sequences of various organisms.

[036] By using the 16-mer glioma Replikin sequence as a template and constructing a recognition proteomic system to visually scan the amino acid sequences of proteins of several different organisms, a new class of peptides, the Replikins, was identified. The present invention provides a metliod for identifying nucleotide or arnino acid sequences that include a Replikin sequence. The method is referred to herein as a 3-point-recognition method. By use of the "3-point recognition" method, described herein below, a new class of peptides was revealed in algae, yeast, fungi, amoebae, bacteria, plant and virus proteins having replication, transformation, or redox functions. Surprisingly, the Replikin peptides were found to be concentrated in larger 'replicating' and 'transforming' proteins (so designated by their investigators, See Table 2). No sequences were found to be identical to the malign in 16-mer peptide.

[037] Table 2 illustrates several Replikin sequences that were identified by the 3-point recognition method of the invention.

Table 2: Examples of Replildns in various Organisms - prototype: Glioma Replikin* kagvaflhkk (SEQ ED No.:!) Tumor 48 Rous sarcoma virus tyrosine-protein kinase kklrhek "Viruses: 49 v-yes, avian sarcoma kklrhdk 50 c-yes, colon cancer, malignant melanoma kklrhdk 51 v-srcC, avian sarcoma kklrhek 52 c-src, colon, mammary, panrcreatic cancer kklrhek 53 Neuroblastoma RAS viral (v-ras) oncogene kqahelak 54 VP1 (major capsid protein) [Polyamavi us sp.] kthrfskh 55 Sindbis knlhekik 56 El [Human papilloamavirus type 71] khrpllqlk 57 v-erbB from AEV and c-erb kspnhvk 58 v-fms (feline sarcoma) knlhlekk 59 c-fms (acute and chronic myelomonocytic tumors) knihlekk 60 large t-antigen I [Polyomavirus sp.l kphlaqslek 61 middle t-antigen [Polyomavirus spJU kqhrelkdk 62 small t-antigen [Polyomavirus spj, kqhrelkdk 63 v-abl, murine acute leukemia kvpvlisptlkh 64 Human T-cell lymphotropic virus typo 2 kslllevdkdish 65 c-kit, GI tumors, small cell lung carcinoma kagitknvkreyh 18 Hepatitis C hyppkpgcivpak Trans66 Transforming protein myb ksgkhlgk forming 67 Transforming protein myc, Burkitt lymphoma kneqlkkk Proteins: 68 Ras-related GTP-binding protein ks evikvih 69 Transforming protein ras (teratocarcinoma) kkkhtvkk 70 TRAF-associated NF'kB activator TANK lcaqkdhlsk 71 RFP transforming protein hlkrvkdlkk 72 Transforming protein D (S.C.) kygspkhrlik 73 Papilloma virus type 11, transforming protein Ttllthilglfarfilf 74 Protein tryosine kinase (EC 2.7.1J12slk kgdhvkhykirk 75 Transforming protein (axl(-)) keklrdvmvdrhk 76 Transforming protein (N-myc) klqarqqqllkkieh 77 Fibroblast growth factor 4 (Kaposi sarcoma) kkgnrvsptmkvth Cancer 78 Matrix metaloproteinase 7 (uterine) keiplhfrk Cell 79 Transcription factor 7-like Id-k hikk Proteins: 80 Breast cancer antigen Y-BR-87 ktrhdplak 81 BRCA-1 -Associated Ring Domain Protein (breast) khhpkdnlik 82 'Autoantigen from a breast tumor' lchkrkkfrqk 83 Glioma Replikin (this study) kagvafinkk 84 Ovarian cancer antigen lchkrkkfrqk 85 EE L leukemia kkkskkhkdk 86 Proto-oncogene tyrosine-protein kinase C-ABLE hksekpalprk 87 Adenomatosis polyposis coli kkkkpsrlkgdnek 88 Gastxic cancer transforming protein kcldigMVsptrnkvth 89 Transforming protein (K-RAS 2B) Jung khkekmskdgkkkkkksk

[038] Identification of an amino acid sequence as a Replikin or as containing a Replikin, i.e., a homologue of the glioma peptide, kagvaflhkk, requires that the three following requirements be met. The peptide sequence must have (1) at least one lysine residue located six to ten residues from another lysine residue; (2) at least one histidine residue; and (3) a composition of at least 6% lysine within an amino acid sequence of 7 to about 50 residues. [039 J Databases were searched using the National Library of Medicine keyword "PubMed" descriptor for protein sequences containing Replikin sequences. Over 4,000 protein sequences were visually examined for homologues. Sequences of all individual proteins within each group of PubMed-classified proteins were visually scanned for peptides meeting the three above-listed requirements. An infrequent occurrence of homologues was observed in 'Virus peptides" as a whole (1.5%) (N=953), and in other peptides not designated as associated with malignant transformation or replication such as "brain peptides" and "neuropeptides" (together 8.5%) (N=845). However, surprisingly, homologues were significantly more frequently identified in large "replicating proteins," which were identified as having an established function in replication in bacteria, algae, and viruses. Even more surprising was the finding that Replikin homologues occurred in 100% of "tumor viruses" (N=250), in 97% of "cancer proteins" (N=401), and in 85% of "transfomiing viruses" (N=248). These results suggest that there are shared properties of cancer pathogenesis regardless of cell type and suggest a role of viruses in carcinogenesis, i.e., conversion of cells from a transformed albeit dormant state to a more virulent actively replicating state.

[040] To permit classification of subtypes of Replikins, additional or "auxiliary specifications" to the basic "3 -point-recognition" requirements may be added: (a) on a structural basis, such as the common occurrence of adjacent di- and polylysines in cancer cell proteins (e.g., transfonning protein P21B(K-RAS 2B), lung, Table 2, SEQ Π) NO.: 89), and other adjacent di-amino acids in TOLL-like receptors, or b) on a functional basis, such as exhibiting ATPase, tyrosine kinase or redox activity as seen in Table 2.

[041] Whether Rephkin structures are conserved or are subject to extensive natural mutation was examined by scanning the protein sequences of various isolates of foot and mouth disease virus (FMDV), where mutations in proteins of these viruses have been well documented worldwide for decades. Protein sequences of FMDV isolates were visually examined for the presence of both the entire Replikin and each of the component Replikin amino acid residues observed in a particular R^likin. For example, in the protein VPl of FMDV type O, the Replikin (SEQ ID NO.: 3) "hkqkivapvk" was found to be conserved in 78% of the 236 isolates reported in PubMed, and each amino acid was found to be conserved in individual isolates as follows: his, 95.6%; lys, 91.8%; gin 92.3%; lys, 84.1%; ile, 90.7%; val, 91.8%; ala, 97.3%; pro, 96.2%; ala, 75.4%; and lys, 88.4%. The high rate of conservation suggests structural and functional stability of the Replikin structure. Similarly, sequence conservation was observed in different isolates of HTV for its Replikins, such as (SEQ ID NO.: 5) "kcfncgkegh" or (SEQ Π) NO.: 6) "kvylawvpahk" in HTV Type 1 and (SEQ ID NO.: 7) "kcwncgkegh" in HTV Type 2 (Table 2). Other examples of conservation are seen in the constant presence of mah'gnin in successive generations, over ten years of tissue culture of glioma cells, and by the constancy of affinity of the glioma Replikin for antimalignin antibody isolated by immunoadsorption from 8,090 human sera from the U.S., U.K., Europe and Asia (e.g., Figure 5 and U.S. Patent 6,242,578 B 1).

[042] As seen in Figure 2, during anaerobic respiration when the rate of cell replication is increased, mah'gnin is enriched. That is, malignin is found to increase not simply in proportion to the increase in cell number and total membrane proteins, but is enriched as much as tenfold in concentration, starting with 3% at rest and reaching 30% of total membrane protein. This clear demonstration of a marked increase in R^likin concentration with glioma cell replication points to and is consistent with the presence of Replikins here sought by the 3-point recognition method and found in the proteins of various organisms which were found by mutation studies and other previous studies to be critical to replication. For example, Replikins were identified in such proteins as "Saccharomyces cerevisiae replication binding protein" (SEQ Π) NO.: 2) (hsikrelgiifdk); the "replication associated protein A of maize streak virus" (SEQ ID NO.: 8) (kyivcareahk) and (SEQ ID NO.: 9) (kekkpskdeimrdiish); the "replication-associated protein of Staphylococcus aureus" (SEQ H) NO.: 10) ( kkektthnk); the "DNA replication protein of bovine herpes virus 4" (SEQ DD NO.: 11) (hkinitngqk); and the "Mealigrid herpes virus 1 replication binding protein" (SEQ Π) NO.: 12) (hkdlyrllmk). Previous studies of tomato leaf curl gemini virus show that the regulation of virus accumulation appears to involve bmding of amino acids 1-160 of the "replicating protein" of that virus to leaf DNA and to other replication protein molecules during virus replication. Analysis of this sequence showed that amino acids 1-163 of this "rephcating protein" contain five Replikins, namely: (SEQ Π) NO.: 13) kfrinaknyfltyph. (SEQ ID NO.: 14) knletpvnklfiricrelh, (SEQ JD NO.: 15) hpniqaaksstdvk, (SEQ ID NO.: 16) ksstdvkaymdkdgdvldh, and (SEQ Π) NO.: 17) kasalnilrekapkdfvlqfh.

[043] Table 2 shows that Replilan-containing proteins also are associated frequently with redox functions, and protein synthesis or elongation, as well as with cell replication. The association with metal-based redox functions, the enrichment of the Replilan-containing glioma malignin concentration during anaerobic replication, and the cytotoxicity of antimalignm at low concentrations (picograms/cell) (Figure 4c-f), all suggest that the Replil ins are related to central respiratory functions, which are perhaps less often subjected to the mutations characteristic of proteins of more superficial location or less central survival function. (044] Of particular interest, it was observed that at least one Replikin per 100 amino acids was found to be present in the hemagglutinin proteins of almost all of the individual strains of influenza viruses examined. The replikin sequences that were observed to occur in the hemagglutinin proteins of isolates of each of the four prevalent strains of influenza virus, influenza B, HlNl, H2N2, and H3N2, for each year that amino acid sequence data are available (1902-2001) are shown in Tables 3, 4, 5 and 6, below.

Table 3 Replikin Sequences present in hemagglutinins of Influenza B viruses in each year for wh available (1902-2001).

Influenza B Replikins Year Detected in Influenza (Peak in Figure 7: EB1 E kshfanlk (SEQ ID NO. 104) 1902,19,24,38,40,43,5159,75,76,77 kshfanlkgtk (SEQ ID NO. 105) 1902,19,24,38,40,43,51,59,75,76,77 kshfanlkgtktrgklcpk (SEQ ID NO. 106) 1902,19,24,38,40,43,5L59,75,76,77 hekygglnk (SEQ ID NO. 107) 1902,19,24,38,40,43,51 59,75,76,72 hekygglnksk (SEQ ID NO. 108) 1902,19,24,38,40,43,51,59,75,76,77 hekygglnkskpyytgehak (SEQ ID NO. 109) 1902,19,24,38,40,43,51,59,75,76,77 hakaigncpiwvk (SEQ ID NO. 110) 1902,19,24,38,40,43,51,59,75,76,72 hakaigncpiwvktplklangtk (SEQ ID NO. 111) 1902,19,24,38,40,43,51,59,75,76,77 hakaigncpiwvktplklangtkyrppak (SEQ ID NO. 112) 1902,19,24,38,40,43,51,59,75,76,77 hakaigpcpiwvktplklangtkyrppakllk (SEQ ID NO. 113) 1902,19,24,38,40,43,51,59,75,76,77 hfanlkgtktrgk (SEQ ID NO. 114) 1919, 76, hfanlkglktrgklcpk (SEQ ID NO. 115) 1919, 76, hsdneiqmvklygdsk (SEQ ID NO. 116) 1919 hsdneiqdkmvklygdskpqk (SEQ ID NO. 117) 1919 hsdneiqmvklygdskpqk (SEQ ID NO. 118) 1919, 24, k(a/v)silhevk (SEQ ID NO. 119) 1919, 40, 59, lcctgtipsakasilh (SEQ ID NO. 120) 1919, kctgtipsakasilhevk (SEQ ID NO. 121) 1919, kygglnkskpyytgeh (SEQ ID NO. 122) 1919 kvwcasgrskvikgslpligeadclh (SEQ ID NO. 123) 1919, 38,40,43, 59,75,76,77 kpyytgehak (SEQ ID NO. 124) 1919, 38,40, 59, kcmgtipsakasil evk (SEQ ID NO. 125) 1924, 43, 75,76,77 hnvinaekapggpyk (SEQ ID NO. 126) 1938, hsdnetqmaklygdsk (SEQ ID NO. 127) 1938, hgvavaadlkstqeaink (SEQ ID NO. 128) 1940, 59, hg avaadlkstqeairjkdtistqeaink (SEQ Π) NO. 129) 1940 klygdskpqkftssangvtth (SEQ Π) NO. 130) 1943, 75,76,77, hsdnetqmaklygdskpqk (SEQ ID NO. 131) 1943, 75,76,77, hfanlkgtqtrgk (SEQ ID NO. 132) 1959 kprsalkckgfh (SEQ ED NO. 133) 19 kskpyytgehakai(g/a)Ecpiwvk (SEQ ID NO. 134) 1. Influenza B has not been responsible for any human pandemic (global distribution). 2. Abbreviation for years: eg. "19" = 1919, "01" = 2001. 3. The first year that a given replikin appears is indicated at the beginning of the series of years in which that replikin has 4. Overlapping replikin sequences are listed separately.

. Increase in number of new replikin structures occurs in years of epidemics (underlined): eg. 1951 and 1977 and correla (number of repliktns per 100 amino acid residues). See Figure 7.

Table 4 HlNl Replikin Sequences present in HINI hermgglutinins of Influenza viruses in each year for which ami HlNl Replikin Year Detecte HlNl Strain (Peak inFigure7 : PI El El. hp(v/i)tigecpkyv(r k)(s t)(t a)k (SEQ ID NO. 135) 1^25,28,30,3^35,47,48.51,52,55,56,57,59,6 hdsnvknly(e g)kv(k/r)(n/s)ql(k r)nnak (SEQ ID NO. 136) 1918. 28,30,31, hdsnvknly(e g)kv(k r)(Ti s)qlk (SEQ ID NO. 137) 1918. 28,30,31, hkc(nn/dd)(a/t e)cmesv(r/k)ngtydypkyseesklnre(e/k)idgvk (SEQ ID NO. 138) 1918. 30, 35, hkc(nn/dd)(a/t e)cmesv(r k)ngtydypkyseesk (SEQ ED NO. 139) 1918. 30, 35, hqn(e g)qgsgyaadqkstqnai(d7n)gitnkvnsviekmntqflavgkefiiklek (SEO 140H918. 28,30,31,35, 5 hqn(e g)qgsgyaadqkstqnai(dn)gitnkvnsviek (SEQ ID NO. 141) 1918. 28,30,3^35, bqn(e g)qgsgyaadqkstqnai(d/n)gitnk (SEQ ID NO. 142) 1918. 28,30,31,35, kfeifpktsswpnh (SEQ ED NO. 143) 1918. kg(n s/t)sypkl(n/s)ksy(v/t)nnkgkevlvlwgvh (SEQ ID NO. 144) 1918. 35, ksy(v/t)nnkgkevlvlwgvh (SEQ ED NO. 145) 1918. 35, hkcnnecmesvkngtydypkyseesklnrekidgvk (SEQ ID NO. 146) 1928, 31, hkcnnecmesvkngtydypkyseesk (SEQ Π) NO. 147) 1928, 31, bkcnnecmesvkngtydypk (SEQ.ID NO. 148) 1928, 31, bkcnnecmesvk (SEQ ED NO. 149) 1928, 31, hngkssfyik/r^lwltie ^knglypnlsksyvnnkek (SEQ ID NO. 150) 1928, hngkssiy(k r)nUwlt(e g)knglypnlsksyvnnk (SEQ ID NO. 151) 1928, 31, bngkssfy(k/r)nUwlt(e g)knglypnlsk (SEQ ID NO. 152) 1928, 31, bngkssfy(k r)nllwlt(e g)k (SEQ ED NO. 153) 1928, 3J, kssfyknllwlteknglypnlsksyvnnkekevlvlwgvh (SEQ ID NO. 154) 1928, 31, knllwUeknglypnlsksyvnnkekevlvlwgvh (SEQIDNO.155) 1928, 31, knglypnisksyvnnkekevlvlwgvh (SEQIDNO.156) 1928, 3_L ksy(v/a)nnkekev(l/-)(v/-)lwgvh (SEQ ID NO.157) 1928, 31, 51, kesswpnhtvtk (SEQIDNO.158) 1928, 31 het(tn)kgvtaacpyagassiynillwlvkkensypklsksyvnnk (SEQIDNO.159) 1930, 35 het(tn)kgvtaacpyagassfyrnllwlvkkensypklsk (SEQIDNO.160) 1930, 35 kfeifpktsswpnevlvlwgvh (SEQIDNO.161) 1930 kerswpkh (SEQIDNO.162) 1947, 51,52,55,56, klsksyvnnkekevlvlwqvh (SEQIDNO.163) 1947, 51 knnkekevlvlwqvh (SEQID O.164) 1947 h(k/n)(g/q)kssfy(i/k)nl^ (SEQID O.165) 1948 h(kn)(g/q)kssiy(r/k)nllwltek (SEQIDNO.166) 1948 hakkssfyk (SEQIDNO.167) 1951. 57,5 hngklcrlkgk (SEQIDNO.168) 1951,52,55,56^7,5 hyklnn(q/g)kk (SEQIDNO.169) 1956, hdiyrdeainnrfqiqgvkltqgyk (SEQ ID NO.170) 1956 kgngcfeifhk (SEQIDNO.171) 1956 klnrliektndkyhqiek (SEQIDNO.172) 1956 klnrliektndkyh (SEQ Π) NO.173) 1956 kchtdkgslsttk (SEQIDNO.174) 1956 kinngdyaklyiwgvh (SEQID O.175) 1956 hngklcrkgiaplqlgk (SEQID O.176) 19 hetnrqvtaacpyagansfirnliwlvkkessypklsk (SEQ ID NO.177) 1 hetnrqvtaacpyagansfEmliwlvkkessypk (SEQ ID NO.178) 1 bpptetdqqslyqnadavifvgsskynrkfk (SEQIDNO.179) 1 hpptstdqqslyqnadayifvgsskynrkfkpeia (SEQIDNO.180) 1 hdiyrdeainnrfqiqgvkitqgyk (SEQIDNO.181) hqneqgsgyaadqkstqhaidgitnkvnsviekmntqftavgk (SEQIDNO.182) hqneqgsgyaadqkstqnaidgitnkvnsviek (SEQID O.183) hqneqgsgyaadqkstqnaingitnkvnsvieknintqftavgkefhklek (SEQID O.184) hngklcrlkgiaplqlgk (SEQID O.185) hkcnnecmesvk (SEQIDNO.186) kfeifpkasswpnh (SEQID O.187) hdsnvknlyekvrsqlmnak (SEQ ED NO.188) kvnsvikkmntqfaavgkefhh (SEQIDNO.189) khngklck (SEQIDNO.190) kkgtsypklsksythnkgkevlvlwgvh (SEQID O.191) kgtsypklsksythnkgkevlvlwgvh (SEQIDNO.192) klsksythnkgkevlvlwgvh (SEQIDNO.193) ksythnkgkevlvlwgvh (SEQID O.194) kgvtascshk (SEQIDNO.195) kgvtascshkgrssfyrnllwlteknglypnlsk (SEQIDNO.196) kgnsypklsksyvnnkekevlvlwgih (SEQIDNO.197) kefhhlek (SEQ ED NO.198) hpptsMqqslyqnadayvivgsskynkkfkpeiatrpk (SEQIDNO.199). hpptstdqqslyqnadayvfvgsskynkkfk (SEQ ED NO.200) hegkssfyrnllwltekegsypklknsyvnk (SEQ EO NO.201) hegkssfymllwltekegsypk (SEQ ED NO.202) hkcdnecmesvrngtydypkyseesk (SEQ ID NO.203) kesswpnhtvtk (SEQ ED NO.204) knllwlteknglypnlsksyvnnkekeilvlwgvh (SEQ ID NO.205) hngkssfy(krn)(n/-)llwlt(eg)(./k)knglypnlsk (SEQIDNO.206) hngkssfyknllwltek (SEQ ID NO.207) htvtkgvtascshngkssfyknllwlteknglypnlsksyvnnkekevlvlwgvh (SEQ ID NO.208) htvt(k/g)gv(ts)ascshngkssfy^ (SEQIDNO.209) htvtkgvtascshngkssfyknllwltek (SEQ ED NO.210) kyvratklrmvtglrnipsiqsrglfgaiagfieggwtgrrudgwygyh (SEQ ID NO. 211) hqneqgsgyaadqkstqnaingitnkvnsiiekmntqftavgk (SEQ ID NO. 212) hqneqgsgyaadqkstqnaingitnkvnsiiek (SEQ ID NO. 213) hqneqgsgyaadqkstqnaingitnk (SEQ ID NO. 214) hsgarsfymllwivkkgnsypk (SEQ ID NO. 215) hsgarsfymllwivkkgnsypklnk (SEQ ID NO. 216) hsgarsfyrnllwivkkgnsypklnksytndk (SEQ ID NO. 217) hsgarsfymllwivkkgnsypklnksytndkgk (SEQ ID NO. 218) htvskgvttscshngk (SEQ ID NO. 219) katswpnhettk (SEQ ID NO. 220) kqvttscshnqk (SEQ ID NO. 221) kgnsypklnksytndkgkevlviwgvh (SEQ ID NO. 222) klnksytndkgkevlviwgvh (SEQ ID NO. 223) ksvtadkgkevlviwgvh (SEQ ID NO. 224) hnqkssfymllwlt(e/q)knglypnlsksy(v/a)annkek (SEQ ED NO. 225) hpitigecplcyvrsak (SEQ ID NO. 226) hqneqgsgyaadqkst ; nsviekmntqftavgk (SEQ ID NO. 227) hqneqgsgyaadqkstqnaingitnkvnsviek (SEQ ID NO.228) Imgkssfymllwlteknglypnlsksyvnnkek (SEQ ID NO. 229) 1. InfluenzaHlNl was responsible for the human pandemic (global distribution) of 1918. 2. Abbreviation for years: eg. "96" = 1996. 3. T¾e first year that a given replikin appears is indicated at the beginning of the series of years in which that replikin has 4. Overlapping replikin sequences are listed separately.

. Increase in number of new replikin structures occurs in years of epidemics (underlined): eg. 1918 and 1977 and correl (number of replikins per 100 amino acid residues). See Figure 7.

Table 5 Replikin Sequences present in hemagglutinins of Influenza H2N2 viruses in years 1957-2 Influenza H2N2 Replikins Year Detected in In (Peak in Figure 8: E2 ) khfekvkilpk (SEQ ID NO. 230) 1957,58,59,60,61,64,^5,68, 78, khllssvkhfekvk (SEQ ED NO. 231) 1957,58,59,60,61, ha(k/q/m)(d n)ilekthngk (SEQ ID NO. 232) 1957,58,59,60,61,64,65,68, 78 ha(k q/m)(d/n)ilekthngklc(k r) (SEQ ID NO. 233) 1957,58,59,60,61,64,65,68, 78, hnvhpltigecpkyvksek (SEQ ID NO. 234) 1957,58,59, 65,68 hpltigecpk vksek (SEQ ID NO. 235) 1957,58,59, 65,68,64,65,68,78 khllssvkhfekvkilpk (SEQ ID NO. 236) 1957,58,59,60,61,64,65,68, 78 krqssginiktegtlencetkcqtplgainttlpfhnvh (SEQ ID NO. 237) 1957. 59, kgsnyp(v/i)ak(g/r)synntsgeqmliiwq(v/i)h (SEQ ID NO. 238) 1957.58.59. 61, bttlgqsracavsgnpsflmmvwltekgsn pvak (SEQ ID NO. 239) 1957 khfekvk (SEQ ID NO. 240) 1957, 59, 65 kiskrgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 241) 1957, 59, 65, krgssgimktegtlencetkcqtplgainttlpfh (SEQ ID NO. 242) 1957. 59, & ktegtlencetkcqtplgainttlpfh (SEQ ID NO. 243) 1957. 59, 65, kiskrgssginiktegtlencetkcqtplgainttlpfh (SEQ ID NO. 244) 1957. 59, 65, ktegtlencetkcqtplgainttlpflin(v/i)b (SEQ ID NO. 245) 1957. 59, 65, kiskrgssgimktegtlencetkcqtplgainttipfh (SEQ ID NO. 246) 1957. 59, 65, .k(e g)sn pvakgsynntsgeqmliiwgvb (SEQ ID NO. 247) 1957. 60, 65 hpltigecpkyvksek (SEQ ID O. 248) 60, 65 kcqtplgaikttlpfh (SEQ ID NO. 249) 1957. 65 hhsndqgsgyaadkestqka(f/i)dgitnkvnsviek- -mntqfeavgkli(n/s)nleklenlnkk (SEQ ID NO. 250) 1961, 65,68, nsndqgsgyaadkestqka(f/i)dgitnkvnsviek- -rnntqfeavgklfin/sjnleklenlnkk (SEQ ID NO. 251) 1961, 65, 68, hsndqgsgyaadkestqkaiffOdgitnk (SEQ ID NO. 252) 1961, 65, 68, hdsnvmlydkvrmqlrdnak (SEQ ID NO. 253) 1964, 68,76, hkcddecrnnsvkngtydypklnrneikgvk (SEQ ID NO. 254) 1964,65,68,76, hkcddecmnsvkngtydypklnmeik (SEQ ID NO. 255) 1964,65,68,76, hkcddecirmsvkngtydypk (SEQ ID NO. 256) 1964,65,68,76, hkcddecmnsvk (SEQ ID NO. 257) 1964,65,68,76, kgsnypvakgsynntngeqiliiwgvh (SEQ ID NO. 258) 1976,78 hsndqgsgyaadkestqkavdgimkvnsviekmntqfeavgk (SEQ ID NO. 259) 1976, krgssgimktegtlencetkcqtplgainttlpfh (SEQ ID O. 260) 1976,78, hpltigecpkyvksek (SEQ ID NO. 261) 1976 hakdilekthngklck (SEQ ID NO. 262) 1976 1. Influenza H2N2 was responsible for the human pandemic (global distribution) of 1957. 2. Abbreviation for years: eg. "58" =1958. 3. The first year that a given replikin appears is indicated at the beginning of the series of years in which that replikin has b 4. Overlapping replikin sequences are listed separately.

. Increase in number of new replikin structures occurs in years of epidemics (underlined): eg. 1957 and 1965 and correla (number of replikins per 100 amino acid residues). See Figure 8.

Table 6 H3N2 Rephkin Sequences present in H3N2 hemagglutinins of Influenza viruses in each year available (1968-2000) Influenza H3N2 Replikins Year Detected in Influenza H3N2 strain Influenz {Peak in Figure 8: P3 E3 hdvyrdealnnrfqikgvelksgyk (SEQ ID NO. 263) 1968.72. 75 htidltdsemnklfertrk (SEQ ID NO. 264) 1968 kfhqiek (SEQ ID NO. 265) 1968.72. ktnekfh(g q)iek (SEQ ID NO. 266) 1968 86 klnr(v/l)iektnekfh (SEQ ID NO. 267) 1968.72. hqiekefsevegriqdlekyvedtk (SEQ ED NO. 268) 1968.72. kicnnphk (SEQ ID NO. 269) 1975 klnrvikktaekfh (SEQ ID NO. 270) 1975 hd(I,v) rdealiiiiifqik(g/q)ve(T/k)s(q/g)yk (SEQ ID NO. 271) 1975.76.77. 86 hqiekefsevegriqdlekyvedtk (SEQ ED NO. 272) 1975 kyvedtkidlwsynaellvalenqh (SEQ ED NO. 273) 1975 kyvkqnslklatgrnmvpekqtrglfgaiag^engwegmidgwygfTh (SEQ ID NO. 274) 1975 kefsevegriqdlekyvedtkidlwsynaellvalenqh (SEQ ID NO. 275) 1975 hqn(s/e)(e/q)g(t s)g(q/y)aad(l/q)k- -stq(a/n)a(i/l)d(q/g)I(n/t)(g/n)kG/v)n(r/s)vi(e/c)k (SEQ ID NO. 276) 1975 hcd(g/q)f(q^)nekwdlf(v i)er(s/t)k (SEQ ID NO. 277) 1975.76.77.78.80.81 ,82,83,84,85,86, htidltdsenmkklfertrk (SEQ ID NO. 278) ksgstypvlkvtr^rmdnfdklviwgvh (SEQ ID NO. 279) 1977 klnwltksgnrypvkvtrnpnndnfdklviwgvh (SEQ ID NO. 280) 1982 htidltdsernnklfektrk (SEQ ID NO. 281) 1986 klnrliekmekfhqtek (SEQ ID NO. 282) 198 htgkssvmrsfopidfcnsecitpnqsipn^ (SEQ ID NO. 283) htgkssvmrsdapidfcnsecirpnqsipndkpfqnvnk (SEQ ID NO. 284) hpstdsdqtslyvrasgrvtvstkrsqqtvipk (SEQ ID NO. 285) kyvedtkidlwsynaellvalenqh (SEQ ID NO.286) klfertrkqlrenaedmgngcfkiyh (SEQ ID NO. 287) krrsiksffsrlnwlh (SEQ ID NO. 288) hpvtigecpky(v/r)kstk (SEQ ID NO. 289) kgrisypkbklsksyiinkkkevlviwgih (SEQ ID NO. 290) klsklsks(v/y)iinkkkevlviwgih (SEQ ID NO. 291) klsks(v/y)iinkkkevlviwgih (SEQ ID NO. 292) 1. Influenza H3N2 was responsible for the human pandemic (global distribution) of 1968. 2. Abbreviation for years: eg. "77" =1977. 3. The first year that a given replikin appears is indicated at the beginning of the series of years in which that re 4. Overlapping replikin sequences are listed separately.

. Increase in number of new replikin structures occurs in years of epidemics (underlined) : eg. 1975 and correl concentration (number of replikins per 100 amino acid residues). See Figure 8.

[045] Both the concentration and type, i.e., composition of Replikins observed were found to relate to the occurrence of influenza pandemics and epidemics. The concentration of Replikins in influenza viruses was examined by visually scanning the hemagglutinin amino acid sequences published in the National Library of Medicine "PubMed" data base for influenza strains isolated world wide from human and animal reservoirs year by year over the past century, i.e., 1900 to 2001. These Replikin concentrations (number of Replikins per 100 amino acids, mean +/- SD) were then plotted for each strain.

[046] The concentration of Replikins was found to directly relate to the occurrence of influenza pandemics and epidemics. The concentration of Replikins found in influenza B hemagglutinin and influenza A strain, ΗΓΝ1, is shown in Figure 7, and the concentration of Replikins found in the two other common influenza virus A strains, H2N2 and H3N2 is shown in Figure 8 (H2N2, H3N2). The data in Figure 8 also demonstrate an emerging new strain of influenza virus as defined by its constituent Replikins (H3N2(R)).

[047] Each influenza A strain has been responsible for one pandemic: in 1918, 1957, and 1968, respectively. The data in Figures 7 and 8 show that at least one replikin per 100 arnino acids is present in each of the influenza hemagglutinin proteins of all isolates of the four common influenza viruses examined, suggesting a function for Replikins in the maintenance of survival levels of replication. In the 1990s, during the decline of the H3N2 strain there were no Replikins present in many isolates of H3N2, but a high concentration of new replikins appeared in H3N2 isolates, which define the emergence of the H3N2(R) strain.

[048] Several properties of Replikin concentration are seen in Figure 7 and Figure 8 to be common to all four influenza virus strains: (1) Concentration is cyclic over the years, with a single cycle of rise and fall occurring over a period of two to thirty years. This rise and fall is consistent with the known waxing and waning of individual influenza virus strain predominance by hemagglutinin and neuraniinidase classification. (2) Peak Replikin concentrations of each influenza virus strain previously shown to be responsible for a pandemic were observed to relate specifically and individually to each of the three years of the pandemics. For example, for the pandemic of 1918, where the influenza virus strain, H 1N1 , was shown to be responsible, a peak concentration of the Replikins in HlNl independently occurred (PI); for the pandemic of 1957, where H2N2 emerged and was shown to be responsible, a peak concentration of the Replikins in H2N2 occurred (P2); and for the pandemic of 1968, where H3N2 emerged and was shown to be the cause of the pandemic, a peak concentration of the Replikins in H3N2 occurred (P3). (3) In the years immediately following each of the above three pandemics, the specific Replikin concentration decreased markedly, perhaps reflecting the broadly distributed immunity generated in each case. Thus, this post-pandemic decline is specific for HlNl immediately following the pandemic (PI) for which it was responsible, and is not a general property of all strains at the time. An increase of Replikin concentration in influenza B repeatedly occurred simultaneously with the decrease in Replikin concentration in HlNl, e.g., EB1 in 1951 and EB2 in 1976, both associated with influenza B epidemics having the highest mortality. (Stuart-Harris, et al., Edward Arnold Ltd. (1985). (4) A secondary peak concentration, which exceeded the primary peak increase in concentration, occurred 15 years after each of the three pandemics, and this secondary peak was accompanied by an epidemic: 15 years after the 1918 pandemic in an HlNl 'epidemic' year (El); eight years after the 1957 pandemic in an H2N2 'epidemic' year (E2); and occurred seven years after the 1968 pandemic in an H3N2 'epidemic' year (E3). These secondary peak concentrations of specific Replikins may reflect recovery of the strain. (5) Peaks of each strain's specific Replikin concentration frequently appear to be associated with declines in Replikin concentration of one or both other strains, suggesting competition between strains for host sites. (6) There is an apparent overall tendency for the Replikin concentration of each strain to decline over a period of 35 years (H2N2) to 60 years (influenza B). This decline cannot be ascribed to the influence of vaccines because it was evident in the case of influenza B from 1901 to 1964, prior to common use of influenza vaccines. In the case of influenza B, Replikin recovery from the decline is seen to occur after 1965, but Replikin concentration declined again between 1997 and 2000 (Figure 7), and this correlates with the low occurrence of influenza B in recent case isolates. H1N1 Replikin concentration peaked in 1978-1979 (Figure 7 ) together with the reappearance and prevalence of the H1N1 strain, and then peaked in 1996 coincident with an H1N1 epidemic. (Figure 7). H1N1 Rephkin concentration also declin* ·-.? between 1997 and 2000, and the presence of H1N1 strains decreased m lsoia, ^-s obtained during these years. For H2N2 Replikins, recovery from a 35 year decline has not occurred (Figure 8), and this correlates with the absence of H2N2 from recent isolates. For H3N2, the Replikin concentration of many isolates fell to zero during the period from 1996 to 2000, but other H3N2 isolates showed a significant, sharp increase in Replikin concentration. This indicates the emergence of a sub-strain of H3N2, which is designated herein as H3N2(R).

[049] Figures 7 and 8 demonstrate that frequently a one to three year stepwise increase is observed before Replikin concentration reaches a peak. This stepwise increase proceeds the occurrence of an epidemic, which occurs concurrently with the R^likin peak. Thus, the stepwise increase in concentration of a particular strain is a signal that that particular strain is the most likely candidate to cause an epidemic or pandemic.

[050] Currently, Replikin concentration in the H3N2(R) strain of influenza virus is increasing (Figure 8, 1997 to 2000). Three similar previous peak increases in H3N2 R^likin concentration are seen to have occurred in the H3N2-based pandemic of 1968 (Figure 8), when the strain first emerged, and in the H3N2-based epidemics of 1972 and 1975 (Figure 8). Each of these pandemic and epidemics was associated with excess mortality. (Ailing, et al., Am J. Epidemiol., 113(l):30-43 (1981). The rapid ascent in concentration of the H3N2(R) subspecies of the H3N2 Replikins in 1997-2000, therefore, statistically represents an early warning of an approaching severe epidemic or pandemic. An H3N2 epidemic occurred in Russia in 2000 (Figure 8, E4); and the CDC report of December 2001 states that currently, H3N2 is the most frequently isolated strain of influenza virus world wide.

(Morbidity and Mortality Weekly Reports (MMWR), Center for Disease Control; 50(48): 1084-68 (Dec.7, 2001).

[051] In each case of influenza virus pandemic or epidemic new Replikins emerge. There has been no observation of two of the same Replikins in a given hemagglutinin in a given isolate. To what degree the emergence of a new Repli n represents mutations versus transfer f om another animal or avian pool is unknown. In some cases, each year one or more of the original RepliMn structures is conserved, while at the same time, new Replikins emerge. For example, in influenza virus B hemagglutinin, five Replikins were constantly conserved between 1919 and 2001, whereas 26 Replikins came and went during the same period (some recurred after several years absence). The disappearance and re-emergence years later of a particular Replikin structure suggests that the Replikins return from another virus host pool rather than through de novo mutation.

[052] ha the case of H1N1 Replikins, the two Replikins present in the P 1 peak associated with the 1 18 pandemic were not present in the recovery E 1 peak of 1933, which contains 12 new Replikins. Constantly conserved Replikins, therefore, are the best choice for vaccines, either alone or in combination. However, even recently appearing Replikins accompanying one year's increase in concentration frequently persist and increase further for an additional one or more years, culminating in a concentration peak and an epidemic, thus providing both an early warning and time to vaccinate with synthetic Replikins (see for example HlNl in the early 1990's, Figure 7).

[053] The data in FIGURES 7 and 8 demonstrate a direct relationship between the presence and concentration of a particular Repli n in influenza protein sequences and the occurrence of pandemics and epidemics of influenza. Thus, analysis of the influenza virus hemagglutinin protein sequence for the presence and concentration of Replikins provides a predictor of influenza pandemics and/or epidemics, as well as a target for influenza vaccine formulation.

[054] Composition of Replikins in Strains of Influenza Virus B: Of a total of 26 Replikins identified in this strain (Table 3), the following ten Replikins are present in every influenza B isolate examined from 1902-2001. Overlapping 158109/2 Replikin sequences are listed separately. Lysines and histidines are in bold type to demonstrate homology consistent with the "3-point recognition." kshfanlk (SEQ ID NO. 104) kshfanlkgtk (SEQ ID NO. 105) kshfanlkgtkttgklcpk (SEQ ID NO. 106) hekygglnk (SEQ ID NO. 107) hekygglnksk (SEQ ID NO. 108) hekygglnkskpyytgehak (SEQ ID NO. 109) hakaigncpiwvk (SEQ ID NO. 1 10) hakaigncpiwvktplklangtk (SEQ ID NO. I l l) hakaigncpiwvktplklangtkyrppak (SEQ ID NO. 1 12) hakaigncpiwvktplklangtkyrppakllk (SEQ ID NO. 1 13)

[055] Tables 3 and 4 indicate that there appears to be much greater stability of the Replikin structures in influenza B hemagglutinins compared with HlNl Replikins. Influenza B has not been responsible for any pandemic, and it appears not to have an animal or avian reservoirs. (Stuart-Harris et al., Edward Arnold Ltd., London (1985)).

[056] Influenza HlNl Replikins: Only one replikin "hp(v/i) tigecpkyv(r/k)(s/t)(t/a)k" is present in every HINT isolate for which sequences are available from 1918, when the strain first appeared and caused the pandemic of that year, through 2000. (Table 4). ("(v/i)" indicates that the amino acid v or i is present in the same position in different years.) Although HlNl contains only one persistent replikin, HlNl appears to be more prolific than influenza B. There are 95 different replikin structures in 82 years on HlNl versus only 31 different Replikins in 100 years of influenza B isolates (Table 4). An increase in the number of new Replikin structures occurs in years of epidemics (Tables 3, 4, 5 and 6) and correlates with increased total Replikin concentration (Figures 7 and 8). 158109/2

[057] Influenza H2N2 Replikins: Influenza H2N2 was responsible for the human pandemic of 1957. Three of the 20 Replikins identified in that strain for 1957 were conserved in each of the H2N2 isolates available for examination on PubMed until 1995 (Table 5). ha(k/q/m)(d/n)ilekthngk (SEQ ID NO. 232) ha(k/q/m)(d/n) ilekthugklc(k/r) (SEQ ID NO. 233) kgsnyp(v/i)ak(g/r)symltsgeqmlllwq(v/i)h (SEQ ID No. 238)

[058] However, in contrast to HIN1, only 13 additional Replikins have been found in H2N2 beginning in 1961. This paucity of appearance of new Replikins correlates with the decline in the concentration of the H2N2 Replikins and the appearance of H2N2 in isolates over the years. (Figure 8).

[059] Influenza H3N2 Replikins: Influenza H3N2 was responsible for the human pandemic of 1968. Five Replikins which appeared in 1968 disappeared after 1977, but reappeared in the 1990s (Table 6). The only Replikin structure which persisted for 22 years was hcd(g/q)f(q/r)nekwdlf(v/i) er(s/t)k, which appeared first in 1977 and persisted through 1998. The emergence of twelve new H3N2 replikins in the mid 1990s (Table 6) correlates with the increase in Replikin concentration at the same time (Figure 8), and with the prevalence of the H3N2 strain in recent isolates. together with the concurrent disappearance of all Replikins from some of these isolates (Figure 8), this suggests the emergence of the new substrain H3N2(R).

[060] Figures 7 and 8 show that influenza epidemics and pandemics correlate with the increased concentration of replikins in influenza virus, which is due to the reappearance of at least one replikin from one to 59 years after its disappearance. Also, in the A strain only, there is an emergence of new strain-specific Replikin compositions (Tables 4-6). Increase in Replikin concentration by repetition of individual replikins within a single protein appears not to occur in influenza virus, but is seen in other organisms.

[061] It has been believed that changes in the activity of different influenza strains are related to sequence changes in influenza hemagglutinins, which in turn are the products of substitutions effected by one of two poorly understood processes: 158109/2 i) antigenic drift, thought to be due to the accumulation of a series of point mutations in the hemagglutinin molecule, or ii) antigenic shift, in which the changes are so great that genetic reassortment is postulated to occur between the viruses of human and non-human hosts. First, the present data suggests that the change in activity of different influenza skeins, rather than being related to non-specific sequence changes, are based upon, or relate to the increased concentration of strain-specific replikins and strain-specific increases in the replication associated with epidemics. In addition, the data were examined for a possible insight into which sequence changes are due to "drift" or "shift", and which due to conservation, storage in reservoirs, then reappearance. The data show that the epidemic-related increase in replikin concentration is not due to the duplication of existing replikins per hemagglutinin, but is due to the reappearance of at least one replikin composition from 1 to up to 59 years after its disappearance, plus in the A strains only, the emergence of new strain- specific replikin compositions (Tables 3-6). Thus the increase in replikin concentration in the influenza B epidemics of 1951 and 1977 are not associated with the emergence of new replikin compositions in the year of the epidemic but only with the reappearance of replikin compositions which had appeared in previous years then disappeared (Table 3). In contrast, for the A strains, in addition to the reappearance of previously disappeared virus replikins, new compositions appear (e.g. in H1N1 in the year of the epidemic of 1996, in addition to the reappearance of 6 earlier replikins, 10 new compositions emerged). Since the A strains only, not influenza B. have access to non-human animal and avian reservoirs, totally new compositions probably derive from non-human host reservoirs rather than from mutations of existing human replikins which appear to bear no, resemblance to the new compositions other than the basic requirements of "3-point recognition" (Tables 3-6). The more prolific nature of HINT compared with B, and the fact that pandemics have been produced by the three A strains only, but not by the B strain, both may also be a function of the ability of the human A strains to receive new replikin compositions from non-human viral reservoirs.

[062] Some replikins have appeared in only one year, disappeared, and not reappeared to date (Tables 3-6). Other replikins disappear for from one to up to 81 years, when the identical replikin sequence reappears. Key replikin V and ¾' amino acids, and the spaces between them, are conserved during the constant presence of particular replikins over many years, as shown in Tables 23-6for the following strain-specific replikins: ten of influenza B, the single replikin of HIN1, and the single replikin of H2N3, as well as for the reappearance of identical replikins after an absence. Despite the marked replacement or substitution activity of other arnino acids both inside the replikin structure and outside it in the rest of the hemagglutinin sequences, influenza replikin histidine (h) appears never to be, and lysine (k) is rarely replaced. Examples of this conservation are seen in the H1N1 replikin"hp(v/i)tigecpkyv(r/k)(s/t)(t/a)k," (SEQ ID NO. 135) constant between 1918 and 2000, in the H3N2 r^likin "hcd(g/q)ii[q,r)nekwdlf(v/i)er(s/t)k" (SEQ ID NO. 277) constant between 1975 and 1998 and in the H3N2 replikin "hqn(s/e)(e/q)g(t/s)g(q/y)aad(^ (SEQ ID NO. 276) which first appeared in 1975, disappeared for 25 years, and then reappeared in 2000. While many amino acids were substituted, the basic replikin structure of 2 Lysines, 6 to 10 residues apart, one histidine, a minimum of 6% lysine in not more than approximately 50 amino acids, was conserved.

[063] Totally random substitution would not permit the persistence of these H1N1 and H3N2 replikins, nor from 1902 to 2001 in influenza B the persistence of 10 replikin structures, nor the reappearance in l993 ofa l919 18mer replikin after an absence of 74 years. Rather than a random type of substitution, the constancy suggests an orderly controlled process, or in the least, protection of the key replikin residues so that they are fixed or bound in some way: lysines, perhaps bound to nucleic acids, and histidines, perhaps bound to respiratory redox enzymes. The mechanisms which control this conservation are at present unknown.

[064] Whether the conservation of replikin structures is unique to influenza or occurs in other virus replikins was examined in foot and mouth disease virus (FMDV) isolates, where extensive mutations in proteins of this virus have been well-documented worldwide over decades. In the protein VP1 of FMDV type 0, the replikin "hkqkivapvk" (SEQ ID NO. 3) was found to be conserved in 78% of the 236 isolates reported in PubMed, and each amino acid was found to be conserved in individual isolates as follows: h,95.6%; k,91.8%; q,92.3%; k.84.1%; i,90.7%; v,91.8%; a..97.3%; p,96.2%; a,75.4%; k,88.4%. Similarly, conservation was observed in different isolates of HTV for its replikins such as "kcfhcgkegh" (SEQ ID NO. 5) or "kvylawvpahk" (SEQ ID NO. 6) in HTV Type 1 and "kcwncgkegh" (SEQ ID NO. 7) in HTV Type 216. The high rate of conservation observed in FMVD and HIV replikins suggests that conservation observed in influenza replikins is a general property of viral replikins.

[065] Data on anti-Replikin antibodies also support Rephkin class unity. An anti-Replikin antibody response has been quantified by immunoadsorption of serum antimahgnin antibody to immobilized malignin (see Methods in U.S. Patent #5,866,690). The abundant production of antimahgnin antibody by administration to rabbits of the synthetic version of the 16-mer peptide whose sequence was derived from maUgnin, absent carbohydrate or other groups, has established rigorously that this peptide alone is an epitope, that is, it is a sufficient basis for this immune response (Figure 3). The 16-mer peptide produced both IgM and IgG forms of the antibody. Antimahgnin antibody was found to be increased in concentration in serum in 37% of 79 cases in the U.S. and Asia of hepatitis B and C, early, in the first five years of infection, long before the usual observance of liver cancer, which develops about fifteen to twenty-five years after infection. Relevant to both infectious hepatitis and HTV infections, transformed cells may be one form of safe haven for the virus: prolonging cell life and avoiding virus eviction, so that the virus remains inaccessible to anti- viral treatment.

[066] Because acJministration of Replikins stimulates the immune system to produce antibodies having a cytotoxic effect, peptide vaccines based on the particular influenza virus Replikin or group of Replikins observed to be most concentrated over a given time period provide protection against the particular strain of influenza most likely to cause an outbreak in a given influenza season., e.g., an emerging strain or re-emerging strain For example, analysis of the influenza virus hemagglutinin amino acid sequence on a yearly or bi-yearly basis, provides data which are useful in formulating a specifically targeted influenza vaccine for that year. It is understood that such analysis may be conducted on a region-by-region basis or at any desired time period, so that strains emerging in different areas throughout the world can be detected and specifically targeted vaccines for each region can be formulated.

[067] Currently, vaccine formulations are changed twice yearly at international WHO and CDC meetings. Vaccine formulations are based on serological evidence of the most current preponderance of influenza virus strain in a given region of the world. However, prior to the present invention there has been no correlation of influenza virus strain specific amino acid sequence changes with occurrence of influenza epidemics or pandemics.

[068] The observations of specific Replikins and their concentration in influenza virus proteins provides the first specific quantitative early chemical correlates of influenza pandemics and epidemics and provides for production and timely administration of influenza vaccines tailored specifically to treat the prevalent emerging or re-emerging strain of influenza virus in a particular region of the world. By analyzing the protein sequences of isolates of strains of influenza virus, such as the hemagglutinin protein sequence, for the presence, concentration and/or conservation of Replikins, influenza virus pandemics and epidemics can be predicted. Furthermore, the severity of such outbreaks of influenza can be significantly lessened by administering an influenza peptide vaccine based on the Replikin sequences found to be most abundant or shown to be on the rise in virus isolates over a given time period, such as about one to about three years.

[069] An influenza peptide vaccine of the invention may include a single Replikin peptide sequence or may include a plurality of Replikin sequences observed in influenza virus strains. Preferably, the peptide vaccine is based on Replikin sequence(s) shown to be increasing in concentration over a given time period and conserved for at least that period of time. However, a vaccine may include a conserved Replikin peptide(s) in combination with a new Replikin(s) peptide or may be based on new Replikin peptide sequences. The Replikin peptides can be synthesized by any method, including chemical synthesis or recombinant gene technology, and may include non-Replikin sequences, although vaccines based on peptides containing only Replikin sequences are preferred. Preferably, vaccine compositions of the invention also contain a pharmaceutically acceptable carrier and/or adjuvant.

[070] The influenza vaccines of the present invention can be administered alone or in combination with antiviral drugs, such as gancyclovir; interferon; interleukin; M2 inhibitors, such as, amantadine, rimantadine; neuraoxinidase inhibitors, such as zanamivir and oseltamivir; and the like, as well as with combinations of antiviral drugs.

[071] Analysis of the primary structure of a Plasmodium farciparum malaria antigen located at the merozoite surface and/or within the parasitophorous vacuole revealed that this organism, like influenza virus, also contains numerous Replikins. However, there are several differences between the observation of Replikins in Plasmodium falciparum and influenza virus isolates. For example, Plasmodium falciparum contains several partial Replikins, referred to herein as "Replikin decoys." These decoy structures contain an abundance of lysine residues, but lack the hisridine required of Replikin structures. It is believed that the decoy structure maximizes the chances that an anti-malarial antibody or other agent will bind to the relatively less important structure containing the lysines, i.e., the Replikin decoys, rather than binding to histidine, which is present in Replikin structure, such as replikins in respiratory enzymes, which could result in destruction of the trypanosome.

[072] Another difference seen in Plasmodium falciparum is a frequent repetition of individual Replikin structures within a single protein, which was not observed with influenza virus. Repetition may occur by (a) sharing of lysine residues between Replikins, and (b) by repetition of a portion of a Replikin sequence within another Replikin sequence.

[073] A third significant difference between Replikin structures observed in influenza virus isolates and Plasmodium falciparum is a marked overlapping of Replikin structures throughout malarial proteins, e.g., there are nine overlapping replikins in the 39 amino acid sequence of SEQ 3D NO. 393 (Replikin concentration = 23.1/100 amino acids); and 15 overlapping replikins in the 41 amino acids of SEQ ID NO. 467 (Replikin concentration = 36.6/100 amino acids). Both of these overlapping Replikin structures occur in blood stage trophozoites and schizonts. In contrast, influenza virus Replikins are more scattered throughout the protein and the maximum Replikin concentration is about 7.5/100 amino acids (Figure 7); and tomato leaf curl gemini virus, which was also observed to have overlapping replikins has only about 3.1/100 ar ino acids.

[074] This mechanism of lysine multiples is also seen in the Replikins of cancer proteins such as in gastric cancer transforming protein, ktkkgnrvsprrnkvth (SEQ ID NO. 88), and in trarisforming protein P21B (K-RAS 2B) of lung, khkekmskdgkkkkkks (SEQ 3D NO. 89).

[075] The relationship of higher Replikin concentration to rapid replication is also confirmed by analysis of HIV isolates. It was found that the slow-growing low titer strain of HIV (NSI, "Bru", which is prevalent in early stage HIV infection has a Replikin concentration of 1.1 (+/- 1.6) Replikins per 100 amino acids, whereas the rapidly-growing high titer strain of HIV (SI, "Lai"), which is prevalent in late stage HIV infection has a Replikin concentration of 6.8 (+/- 2.7) Replikins per 100 amino acid residues.

[076] The high concentration of overlapping Replikins in malaria, influenza virus and cancer cells is consistent with the legendary high and rapid replicating ability of malaria organisms. The multitude of overlapping Replikins in malaria also provides an opportunity for the organism to flood and confuse the immune system of its host and thereby maximize the chance that the wrong antibody will be made and perpetuated, leaving key malaria antigens unharmed.

[077] As in the case of influenza virus, for example, peptide vaccines based on the Replikin structure(s) found in the malaria organism can provide an effective means of preventing and/or treating malaria. Vaccination against malaria can be achieved by adniinistering a composition containing one or a mixture of Replikin structures observed in Plasmodium falciparum. Furthermore, antibodies to malaria Replikins can be generated and aclniinistered for passive immuni ty or malaria detection purposes.

[078] Table 7 provides a list of several Plasmodium falciparum Replikin sequences. It should be noted that this list is not meant to be complete. Different isolates of the organism may contain other Replikin structures.

Table 7 Malaria replikins a) Primary structure of a Plasmodium falciparum malaria antigen located at the merozoite surface and within the parasitophorous vacuole a) i) DECOYS: (C-Terminal) keeeekekekekekeekekeekekeekekekeekekekeekeeekk (SEQ ID NO. 293), or keeeekekekekekeekekeekekeekekekeekekekeekeeekkek (SEQ ID NO. 294), or keeeekekekekekeekekeekekekeekekeekekeekeekeeekk (SEQ ID NO. 295), or keeeekekek (SEQ ID NO. 296) ii) REPLIKINS: Hkklikalkkniesiqnkk (SEQ ID NO. 297) hkklikalkkniesiqnkm (SEQ ID NO. 298) hkklikalkk (SEQ ID NO. 299) hkklikalk (SEQ ID NO. 300) katysfvntldd iislksqghkk (SEQ ID NO. 301) katysfVntkkkiislksqghk (SEQ ID NO. 302) katysfvntkkkiislksqgh (SEQ ID NO. 303) htyvkgkkapsdpqca dikeeckellkek (SEQ ID NO. 304) kuslksqghk (SEQ ID NO. 305) l kkkfeplkngnvsetiklih (SEQ ID NO. 306) kkkfeplkngnvsetiklih (SEQ ID NO. 307) kkfeplkngnvsetiklih (SEQ ID NO. 308) kngnvsetiklih (SEQ ID NO. 309) kl gnkdkk (SEQ ID NO. 310) kvkkigvtlkkfeplkngn^ (SEQ ID NO. 311) hHyknksynplUscvldanr^ (SEQ ID NO. 313) MiykiiksynpMscvkkmm (SEQ ID NO. 315) h yl nksynplUscvldannmlk (SEQ ID NO. 316) ksannsanngWamaeemknlv^ (SEQ ID NO. 317) kknnaeemknlvnflqsω k : alldcniesiqIlka (SEQ ID NO. 318) knlvnflqshkMikalldaiiei* akkh (SEQ ID NO. 319) kMikalkkruesiqnkkh (SEQ ID NO. 320) klikalkkniesiqnkkh (SEQ ID NO. 321) kkniesiqnkkh (SEQ ID NO. 322) kniesiqnkkh (SEQ ID NO. 323) knnaeemknlvnflqsh (SEQ ID NO. 324) kldikalkkmesiqnkkqghkk (SEQ ID NO. 325) kknnaeemknlvnflqshk (SEQ ID NO. 326) kimaeemknlvnilqsh (SEQ ID NO. 327) klikalkkiriesiqnkkqghkk (SEQ ID NO. 328) kvkkigvtUd feplJmgnvsetiMih (SEQ ID NO. 329) kngnvsetiklih (SEQ ID NO. 330) klihlgnkdkk (SEQ ID NO. 331) ksaimsaniigklainaeeiriMviiilqsh (SEQ ID NO. 332) kkmiaeemknlvnflqsh (SEQ ID NO. 333) kklikalkkniesiqnldch (SEQ ID NO. 334) kalkkniesiqnkkh (SEQ ID NO. 335) kkniesiqnkkh (SEQ ID NO. 336) kelinnqkatysfvntkkkiislksqgh (SEQ ID NO. 337) ksqghkk (SEQ ID NO. 338) kkkiislksqgh (SEQ ID NO. 339) kkiislksqgh (SEQ ED NO. 340) kkniesiqnkkh (SEQ ID NO. 341) kniesiqnkkh (SEQ ID NO. 342) htyvkgkkapsdpqcadikeeckellkek (SEQ ID NO. 343) htyvkgkkapsdpqcadikeeckellk (SEQ ID NO. 344 ) b) "liver stage antigen-3" gene="LSA-3" Replikins henvlsaalentqseeekkevidvieevk (SEQ ID NO. 345) kenvvttilel veettaeivttfsnileeiqentitadtieekleelh (SEQ ID NO. 346) hylqqmkekfskek (SEQ ID NO. 347) ylqqn ekfskeknimvievtiikaekkgnvqvtiikte (SEQ ID NO. 348) hylqqmkekfskeknmvievtakaekkgnvqvtnktekt^ (SEQ ID NO. 350) hylqqmkekfskeknimvievtriiaekkgnvqvtn^ (SEQ ID NO.351) hvdevmkvvqki(ikev<_Jkev^^ (SEQ ID NO. 352) hvdevmkvvqkidkevdkevs^ (SEQ ID NO. 353) hvdevnikyvqMdkevdkevskalesl ndvtnvlkqnqdffs (SEQ ID NO. 354) hvdevmkyvqkidkevdkevskaleskndvtnvlk (SEQ ID NO. 355) hvdevmkyvqkidkevdkevskalesk (SEQ ID NO. 356) hvdevmkyvqkidkevdkevsk (SEQ ID NO. 357) hvdevmkyvqkidkevdk (SEQ ID NO. 358) hvdevmkyvqkidk (SEQ ID NO. 359) kdevidUvqkekriekvkakkkklekkveegvsglkkh (SEQ ID NO. 360) kvkal kkklekkveegvsglkkh (SEQ ID NO. 361) kakl kklekkveegvsglkkh (SEQ ID NO. 362) kkkklekkveegvsglkkh (SEQ ID NO. 363) kkklekkveegvsglkkh (SEQ ID NO. 364) kklekkveegvsglkkh (SEQ ID NO. 365) klekkveegvsglkkh (SEQ ID NO. 366) kkveegvsglkkh (SEQ ID NO. 367) kveegvsglkkh (SEQ ID N0.368) hveqnvyvdvdvpamkdqflgilneagglkernfMedvfksesdvitveeikdepvqk (SEQ ID NO.369) hkgleeddleevddlkgsildmlkgdmelgdmdkesledvttklgerveslk (SEQ ID NO. 370) hikgleeddleevdd^sildmlkgdmelgdm&esledvttk (SEQ ID NO. 371) hikgleeddleevddlkgsildmlkgdmelgdmdk (SEQ ID NO. 372) hikgleeddleevddlkgsildmlk (SEQ ID NO. 373) hiisgdadvlssalgmdeeqmldrkkaqipk (SEQ ID NO. 374)· hditttldewelkdveedkiek (SEQ ID NO. 375) kkleevhelk (SEQ ID NO. 376) kleevhelk (SEQ ID NO. 377) ktietdileekkkeiekdh (SEQ ID NO. 378) kkeiekdhfek (SEQ ID NO. 379) kdhfek (SEQ ID NO. 380) kfeeeaeeikh (SEQ ID NO. 381) c) 28 KDA ookinete surface antigen precursor Replikins: kdgdtkctlecaqgkkcikl-J sdlmhksdh^ (SEQ ID NO. 382) kdgdtkctlecaqgkkcikhksdht^ (SEQ ID NO. 383) kdgdtkctlecaqgkkcikhJcsdhnhksdhnl^ (SEQ ID NO. 384) kdgdtkctlecaqgkkcikbksdhnhksd nhk (SEQ ID NO. 385) kdgdtkctlecaqgkkcikhksdhnhk (SEQ ID NO. 386) kdgdtkctlecaqgkkcikhk (SEQ ID NO. 387) kdgdtkctlecaqgkk (SEQ ID NO. 388) kdgdtkctlecaqgk (SEQ ID NO. 389) kciqaecnykecgeqkcvwdgih (SEQ ID NO. 390) kecgeqkcvwdgih (SEQ ID NO. 391) Meckcmdyvltnryecepknkctsledtnk (SEQ ID NO. 392) d) Blood stage trophozoites and schizonts Replikins: ksdhnhksdhri ksd nhksdhnhksdp (SEQ ID NO. 393) ksdhnhksdlmhksdlmhks^^ (SEQ ID NO. 394) VsdhnhlcsiHmhVsHpnTilfkknT nnnV (SEQ ID NO. 395) ksdhnbksdpTihkkknnnnnk (SEQ ID NO. 396) kkknnnnnkdnksdpnhk (SEQ ID NO. 397) kknrinnnkdpksdpnbk (SEQ ID NO. 398) knnnnnkdnksdpnhk (SEQ ID NO. 399) kdnksdpnhk (SEQ ID NO. 400) ksdpnhk (SEQ ID NO. 401) hslyalqqneeyqkvknekdqneikkikqHeknk (SEQ ID NO. 402) hslyalqqneeyqkvbiekdqneikkik (SEQ ID NO. 403) hslyalqqneeyqkvknekdqneikk (SEQ ID NO. 404) hslyalqqneeyqkvknekdqneik (SEQ ID NO. 405) hklenleemdk iSEQ ID ^ 406) khfddntneqk (SEQ ID l ,< 407) kkeddekh (SEQ ID NO. 408) keennkkeddekh (SEQ ID NO. 409) ktssgilnkeennkkeddekh (SEQ ID NO. 410) knihikk (SEQ ID NO. 411) hikkkegidigyk (SEQ ID NO. 412) kkmwtckl (irikgneitkaili (SEQ ID NO. 413 ) kkgiqwnllkkmwtcklwdnkgneilknih (SEQ ID NO. 414 ) kekkdsnenrkkkqkedkknpriklkkieyb^ (SEQ ID NO. 415) kkdsnenxlddcqkedkknpnklkkieytnkit^ (SEQ ID NO. 416) kdsnenrkkkqkedklmpnl<^ (SEQ JD NO. 417) kkqkedkknpnklkkieytnk^^ (SEQ ID NO. 418) kqkedkknprikllddeytrito (SEQ ID NO. 419) kedlcknpnklkkdeytnH^ (SEQ ID NO. 420) lddeytnkithffkaknnkqqnnvth (SEQ ID NO. 422) kieytokithiikaknn qqnnvth (SEQ ID NO. 423) kitnffkaknnkqqnnvth (SEQ ID NO. 424) hkrmedikndnskdikndnskdikndnskdi^ (SEQ ID NO. 425 ) hknnedikndnskdikndnskdikndnskdik^ (SEQ ID NO. 426) bJamedikndnskdikndnskdito (SEQ ID NO. 427) hkimedikndnskdikndnskdikndnskdik (SEQ ID NO. 428) hkrmedikndbaskdikndnskdikndnsk (SEQ ID NO. 429) hJcnnedikndnskdikndnskdik (SEQ ID NO. 430) hknnedikndnskdikndnsk (SEQ ID NO. 431) hknnedikndnskdik (SEQ ID NO. 432) hknnedik (SEQ ID NO. 433) kkyddlqnkynilnldknsleeknee^^ (SEQ ID NO. 434) kyddlqnkyriilnJdJmsleek^ (SEQ ID NO. 435) kynilnldknsleekneelkkyh (SEQ ID NO. 436) klknsleekneelkkyb. (SEQ ID NO. 437) knsleekneelkkyh (SEQ ID NO. 438) kneelkkyh (SEQ ID NO. 439) bingnnqdinenvynikpqefkeeeeedismvntkk (SEQ ID NO.440) knsnelkrindnffkl (SEQ ID NO. 441) ^clykkckisqclykkckisqvwwcmpvkdtfetyermvlnskienm (SEQ ID NO. 442) hirmeytnknpkncllykneemynd (SEQ ID NO. 443) hinneytnlmpkncllyknee (SEQ ID NO. 444) hinneytnknpkncllyk (SEQ ID NO. 445) laiktnqskgvkgeyekkketngh (SEQ ID NO. 446) ktnqskgvkgeyekkketagh (SEQ ID NO. 447) kgvkgeyekkketngh (SEQ ID NO. 448) kgeyekkketngh (SEQ ID NO. 449) ksgmytnegrikscecsykkkssssnkvh (SEQ ID NO. 450) kscecsykkkssssnkvh (SEQ ID NO. 451) kkkssssnkvh (SEQ ID NO. 452) kkssssnkvh (SEQ ID NO. 453) kssssnkvh (SEQ ID NO. 454) himlksgmytnegnkscecsykkkssssnk (SEQ ID NO. 455) himlksgmytnegnkscecsykkk (SEQ ID NO. 456) himlksgmytnegnkscecsykk (SEQ ID NO. 457) himlksgmytnegnkscecsyk (SEQ ID NO. 458) kplaJdrkrel tqinktkyergdvudnteiqkiikdyhetb^ (SEQ ID NO. 459) krektqin kyergdviidnteiqkiikdyhetkvhkldh (SEQ ID NO. 460) ktqiiDitkyergdvudDteiq& (SEQ ID NO. 461) kplaldrkrektqmktkyergdviidnteiqkii^ (SEQ ID NO. 462) kplaldrkrektqiiikt^ (SEQ ID NO. 463) klrkrektqinktkyergdvii(ijiteiqkiiixdyh (SEQ ID NO. 464) krektqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 465) ktqinktkyergdviidnteiqkiiirdyh (SEQ ID NO. 466) kkdkekMcdsnemkkkqkedkl^ (SEQ ID NO. 467) kdkekkkdsnemkkkqkedkknpn^ (SEQ ID NO. 468) kekkkdsnerffkkkqkedkknpnd (SEQ ID NO. 469) kkkdsneiirkkkqkedklmpndi (SEQ ID NO. 470) ldcdsnerirkkkqkedkknpndn^ (SEQ ID NO. 471) kdsnenrkkkqkedkknpndnklkkieytnkiih (SEQ ID NO. 472) W kqkedkknpndnkllddeytnldth (SEQ ID NO. 473) kkqkedkknpnclnklkkieytnkith (SEQ ID NO. 474) kqkedkknpndnkllddeytnkith (SEQ ID NO. 475) kedkknpndnklkkieytnkith (SEQ ID NO. 476) kknpndnklkkieytnkith (SEQ ID NO. 477) knpncinklkkieytnkith (SEQ ID NO. 478) klkkieytakith (SEQ ID NO. 479) kkieytnkith (SEQ ID NO. 480) kieytnkith (SEQ ID NO. 481) hgqikiedvnneoinneqinknl^ideekmdiskskslk (SEQ ID NO. 483) hgqiMedvmenjmeqmkrikyndeekmdisksk (SEQ ID NO. 484) hgqildedvmeninneqmknkyndeekmdisk (SEQ ID NO. 485) kkyddlqnkynilnklki^ (SEQ ID NO. 486) kyddlqnkymlnldknsleekneelkkyh (SEQ ID NO. 487) kynilnklknsleekneelkkyh (SEQ ID NO. 488) klknsleekneelkkyh (SEQ ID NO. 489) knsleekneelkkyh (SEQ ID NO. 490) kneelkkyh (SEQ ID NO. 491) hmgnnqdinenvynikpqefkeeeeedismvntk^ (SEQ ID NO. 492) ktnI>Tuyriiiknddk (SEQ ID NO. 493) knsnelkrindnffkl (SEQ ID NO. 494) lffindnfEklh (SEQ ID NO. 495) MnneytnknplmcUykneemyndmikdyinsm^ (SEQ ID NO. 497) hinneytnknpkncllyk (SEQ ID NO. 498) kcldsqvAvwcmpvkdtfetyernnvtaskieiinieldph (SEQ ID NO. 500) kienniekiph (SEQ ID NO. 501) knktagskgvkgeyekkketngh (SEQ ID NO. 502) ktngskgvkgeyekkketngh (SEQ ID NO. 503) kgvkgeyekkketngh (SEQ ED NO. 504) kgeyekkketngh (SEQ ID NO. 505) ktiekinksliswffeeldeidkpl (SEQ ID NO. 506) kinkskswffeeldeidkplakk^ (SEQ ID NO. 507) ^la rkrektqinl^ (SEQ ID NO. 508) himlksqmytnegnlcscecsykkkssssnkvh (SEQ ID NO. 509) ldrkrektqinktkyergdviidnteiqkiirdyh (SEQ ID NO. 510) krel tqij-Jdkyergdviidnteiqkiirdyh (SEQ ID NO. 511) qinktkyergdviidnteiqkiirdyh (SEQ ID NO. 512) kplakkkrektqkktty^^ (SEQ ID NO. 513) kkkrektqiiiktkyergdvu^ (SEQ ID NO. 514) krektqinktkyergdvudnteiqkikdyhtlnvhkldli(SEQ ID NO. 515) ktqiiilctkyergdviiclnteiqkiirdyhtln^ (SEQ ID NO. 516) kplaklrkrektqinJdJcyergdviidnteiqkikdy (SEQ ID NO. 517) krelrtqiiiktkyergdvudnteiqkiirdyhtlnvh (SEQ ID NO. 519) ktqinkt-^ergdviiiinteiqkiirdyhtlnvh (SEQ ID NO. 520) himlksqmytnegnkscecsykkkssssnkvli (SEQ ID NO. 521) ksqmytnegnkscecsykkkssssnkvh (SEQ ID NO. 522) kscecsykkkssssnkvh (SEQ ID NO. 523) kkkssssnkvh (SEQ ID NO. 524) kkssssnkvh (SEQ ID NO. 525) kssssnkvh (SEQ ID NO. 526) himlksqmytaegnkscecsykkkssssnk (SEQ ID NO. 527) bimlksqmytnegnkscecsykkk (SEQ ID NO. 528) himLksqmytaegnkscecsykk (SEQ ID NO. 529) bimlksqmytnegnkscecsyk (SEQ ID NO. 530) hnnhniqiykHkrin mnphk-yrnyhdnmskri^ek (SEQ ID NO. 531) hnnhniqiykdkrinfhm (SEQ ID NO. 532) hriribjnqiykdlainto (SEQ ID NO. 533) Woanyhanmsknertek (SEQ ID NO. 534) hkvmyhdnmsk (SEQ ID NO. 535) Other microorganisms found to contain numerous Replikin structures are Bacillus anthracis, the organism responsible for anthrax infections, in which eight different replikins were identified ; and small pox virus, in which five different Replikins were identified. The eight Bacillus anthracis peptides are present in the Anthrax Toxin Lethal Factor Protein pXOl-107 and have the amino acid sequence of SEQ ID NO. 91, SEQ ID NO.92, SEQ ID NO. 93, SEQ ID NO. 94, SEQ ID NO. 95, SEQ ID NO. 96, SEQ ID NO. 97 and SEQ ID NO. 98, respectively. The five small pox virus peptides are present in the Small Pox Virus Surface Antigen S Precursor Protein, which purportedly enhances Small Pox Virus replication. The five peptides have the amino acid sequence of SEQ ID NO. 99, SEQ ID NO. 100, SEQ ID NO.101, SEQ ID NO. 102 and SEQ H> NO. 103, respectively.

[079] Synthetic Replikin vaccines, based on Replikins such as the glioma Replikin (SEQ H> NO.: 1) "kagvaflhkk" or the hepatitis C Replikin (SEQ ID NO.: 18) "hyppkpgcivpak", or HIV Replikins such as (SEQ ID NO.: 5) "kcfncgkegfa" or (SEQ ID NO.: 6) "kvylawvpahk" or preferably, an influenza vaccine based on conserved and/or emerging or re-emerging Replikin(s) over a given time period may be used to augment antibody concentration in order to lyse the respective virus infected cells and release virus extracellularly where chemical treatment can then be effective. Similarly, a malaria vaccine, based on Replikins observed in Plasmodium falciparum malaria antigens on the merozoite surface or within the parasitophorous vacuole, for example, can be used to generate cytotoxic antibodies to malaria. Vaccines based on the Replikin structures identified in small pox virus, or Bacillus anthracis, or any pathological organism in which Replikins are identified, can be generated and administered to prevent the respective disease.

Recognin and/or Replikin peptides may be administered to a subject to · induce the immune system of the subject to produce anti-Replikin antibodies.

Generally, a 0.5 to about 2 mg dosage, preferably a 1 mg dosage of each peptide is administered to the subject to induce an immune response. Subsequent dosages may be adniinistered if desired.

[080] In another embodiment of the invention, isolated Replikin peptides may be used to generate antibodies, which may be used, for example to provide passive immunity in an individual. Passive immunity to the strain of influenza identified by the method of the invention to be the most likely cause of future influenza infections may be obtained by administering antibodies to Replikin sequences of the identified strain of influenza virus to patients in need. Similarly, passive immunity to malaria may be obtained by administering antibodies to Plasmodium falciparum RephTkin(s); immunity to Small pox is achieved by administering antibodies to small pox virus Replin(s); irnmunity to anthrax is achieved by administering antibodies to Bacillus anthracis Replikin(s); and the like.

[081] Various procedures known in the art may be used for the production of antibodies to Replikin sequences. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, humanized, single chain, Fab fragments and fragments produced by an Fab expression library. Antibodies that are linked to a cytotoxic agent may also be generated. Antibodies may also be administered in combination with an antiviral agent. Furthermore, combinations of antibodies to different Replikins may be administered as an antibody cocktail.

[082] For the production of antibodies various host animals may be immunized by injection with a Replikin peptide or a combination of Replikin peptides, including but not limited to rabbits, mice, rats, and larger mammals. Various adjuvants may be used to enhance the immunological response, depending on the host species, including but not limited to Freund's (complete and incomplete), mineral gels, such as aluminum hydroxide, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, key limpet hemocyanin, dintrophenol, and potentially useful human adjuvants such as BCG and Corynebacterium parvum. [083] Monoclonal antibodies to Replikins may be prepared by using any technique that provides for the production of antibody molecules. These include but are not limited to the hybridoma technique originally described by Kohler and Milstein, (Nature, 1975, 256:495-497), the human B-cell hybridoma technique (Kosbor et al., 1983, Immunology Today, 4:72), and the EBV hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). In addition, techniques developed for the production of chimeric antibodies (Morrison et al., 1984, Proc. Nat. Acad. Sci USA, 81:6851-6855) or other techniques may be used. Altematively, techniques described for the production of single chain antibodies (US 4,946,778) can be adapted to produce RepHkin-specific single chain antibodies.

[084] Particularly useful antibodies of the invention are those that specifically bind to Replikin sequences contained in peptides and/or polypeptides of influenza virus. For example, antibodies to any of peptides observed to be present in an emerging or re-emerging strain of influenza virus and combinations of such antibodies are useful in the treatment and/or prevention of influenza. Similarly, antibodies to any replikins present on malaria antigens and combinations of such antibodies are useful in the prevention and treatment of malaria.

[085] Antibody fragments which contain binding sites for a Replikin may be generated by known techniques. For example, such fragments include but are not limited to F(ab')2 fragments which can be produced by pepsin digestion of the antibody molecules and the Fab fragments that can be generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, Fab expression libraries can be generated (Huse et al., 1989, Science, 246:1275-1281) to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity.

[086] The fact that antimahgnin antibody is increased in concentration in human malignancy regardless of cancer cell type (Figure 5), and that this antibody binds to malignant cells regardless of cell type now may be explained by the presence of the Replikin structures herein found to be present in most malignancies (Figure 1 and Table 2). Population studies have shown that antimalignin antibody increases in concentration in healthy adults with age, and more so in high-risk families, as the frequency of cancer increases. An additional two-fold or greater antibody increase which occurs in early malignancy has been independently confirmed with a sensitivity of 97% in breast cancers 1-10 mm in size. Shown to localize preferentially in malignant cells in vivo, histochemically the antibody does not bind to normal cells but selectively binds to (Figure 4a,b) and is highly cytotoxic to transformed cells in vitro (Figure 4c-f). Since in these examples the same antibody is bound by several cell types, that is, brain glioma, hematopoietic cells (leukemia), and small cell carcinoma of lung, malignant Replikin class unity is again demonstrated.

[087] Antimalignin does not increase with benign proliferation, but specifically increases only with malignant transformation and replication in breast in vivo and returns from elevated to normal values upon elimination of malignant cells (Figure 5). Antimalignin antibody concentration has been shown to relate quantitatively to the survival of cancer patients, that is, the more antibody, the longer the survival. Taken together, these results suggest that anti-Replikin antibodies may be a part of a mechanism of control of cell transformation and replication. Augmentation of this immune response may be useful in the control of replication, either actively with synthetic Replikins as vaccines, or passively by the administration of anti-Replikin antibodies, or by the introduction of non-immune based organic agents, such as for example, carbohydrates, lipids and the like, which are similarly designed to target the Replikin specifically. For organisms such as diatom plankton, foot and mouth disease virus, tomato leaf curl gemini virus, hepatitis B and C, HIV, influenza virus and malignant cells, identified constituent Replikins are useful as vaccines, and also may be usefully targeted for diagnostic purposes. Blood collected for transfusions, for example, may be screened for contamination of organisms, such as HTV, by screening for the presence of Replikins shown to be specific for the contamination organism. Also, screening for Replikin structures specific for a particular pathological organism, e.g., anthrax., leads to diagnostic detection of the organism in body tissue or in the environment.

[088] The Replikin sequence structure is associated with the function of replication. Thus, whether the Replikins of this invention are used for targeting sequences that contain Replikins for the purpose of diagnostic identification, promoting replication, or inhibiting or attacking replication, for example, the structure-function relationship of the Replikin is fundamental. Thus, while the structure of the Replikin may be a part of a larger protein sequence, which may have been previously identified, it is preferable to utilize only the specific Replikin structure when seeking to induce antibodies that will recognize and attach to the Replikin fragment and Even though the larger protein sequence may be known in the art as having a "replication associated function," vaccines using the larger protein often have failed or proven ineffective, even though they contain one or more Replikin sequences.

[089] Although the present inventors do not wish to be held to a single theory, the studies herein suggest that the prior art vaccines are ineffective because they are based on the use of the larger protein sequence. The larger protein sequence invariably has one or more epitopes (independent antigenic sequences that can induce specific antibody formation); Replikin structures usually comprise one of these potential epitopes. The presence of other epitopes within the larger protein may interfere with adequate formation of antibodies to the Replikin, by "flooding" the immune system with irrelevant antigenic stimuli which may preempt the Replikin antigens, See, e.g., Webster, R.G., J. Immunol., 97(2):177-183 (1966); and Webster et al., J. Infect. Dis., 134:48-58, 1976; Klenerman et al, Nature 394:421-422 (1998) for a discussion of the well-known phenomenon "original antigenic sin"). The formation of an antibody to a non-Replikin epitope may allo bmding to the cell, but not necessarily lead to cell destruction. The presence of structural "decoys" on the C-termini of malaria proteins is another aspect of this ability of other epitopes to interfere with binding of effective anu^R^likin antibodies, since the decoy epitopes have many lysine residues, but no histidine residues. Thus, decoy epitopes may bind anti-Replikin antibodies, but keep the antibodies away from histidine - bound respiratory enzymes. [090J It is well known in the art that in the course of antibody production against a "foreign" protefc the protein is first hydrolyzed into smaller fragments. Usually fragments contar;: iig from about six to ten amino acids are selected for antibody formation. Thus, if hydrolysis of a protein does not result in Replikin- containing fragments, anti-Replikin antibodies will not be produced. In this regard, it is interesting that Replikins contain lysine residues located six to ten amino acids apart, since lysine residues are known to bind to membranes.

[091] Furthermore, Replikin sequences contain at least one histidine residue. Histidine is frequently involved in binding to redox centers. Thus, an antibody that specifically recognizes a Replikin sequence has a better chance of inactivating or destroying the cell in which the Replikin is located, as seen with anti-malignin antibody, which is perhaps the most cytotoxic antibody yet described, being active at picograms per cell.

[092] One of the reasons that vaccines directed towards a particular protein antigen of a disease causing agent have not been fully effective in providing protection against the disease (such as foot and mouth vaccine which has been developed against the VP 1 protein or large segments of the VP 1 protein) is that antibody to the Replikins have not been produced. That is, either epitopes other than Replikins present in the larger protein fragments may interfere according to the phenomenon of "original antigenic sin", and/or because the hydrolysis of larger protein sequences into smaller sequences for processing to produce antibodies results in loss of integrity of any Replikin structure that is present, e.g., the Replikin is cut in two and/or the histidine residue is lost in the hydrolytic processing. The present studies suggest that for an effective vaccine to be produced, the Replikin sequences, and no other epitope, should be used as the vaccine. For example, a vaccine of the invention can be generated using any one of the Replikin peptides identified by the three point recognition system. Particularly preferred peptides for an influenza vaccine include peptides that have been demonstrated to be conserved over a period of one or more years, preferably about three years or more, and/or which are present in a strain of influenza virus shown to have the highest increase in concentration of Replikins relative to Replikin concentration in other influenza virus strains, e.g., an emerging strain. The increase in Replikin concentration preferably occurs over a period of at least about six months to one year, preferably at least about two years or more, and most preferably about three years or more. Among the preferred Replikin peptides for use in an influenza virus vaccine are those replikins observed to "re-emerge" after an absence from the hemagglutinin amino acid sequence for one or more years.

[093] The Replikin peptides of the invention, alone or in various combinations are ad-ministered to a subject, preferably by i.v. or intramuscular injection, in order to stimulate the immune system of the subject to produce antibodies to the peptide. Generally the dosage of peptides is in the range of from about 0.1 μg to about 10 mg, preferably about 10 μg to about 1 mg, and most preferably about 50 g to about 500 ug. The skilled practitioner can readily determine the dosage and number of dosages needed to produce an effective immune response.

[094] Replikin DNA or RNA may have a number of uses for the diagnosis of diseases resulting from infection with a virus, bacterium or other Replikin encoding agent. For example, Replikin nucleotide sequences may be used in hybridization assays of biopsied tissue or blood, e.g., Southern or Northern analysis, including in situ hybridization assays, to diagnose the presence of a particular organism in a tissue sample or an environmental sample, for example. The present invention also contemplates kits containing antibodies specific for particular R^likins that are present in a particular pathogen of interest, or containing nucleic acid molecules (sense or antisense) that hybridize specifically to a particular Replikin, and optionally, various buffers and/or reagents needed for diagnosis.

[095] Also within the scope of the invention are oligoribonucleotide sequences, that include antisense RNA and DNA molecules and ribozymes that function to inhibit the translation of Replikin- or recognm-containing mRNA. Both antisense RNA and DNA molecules and ribozymes may be prepared by any method known in the art. The antisense molecules can be incorporated into a wide variety of vectors for delivery to a subject. The skilled practitioner can readily determine the best route of delivery, although generally i.v. or i.m. delivery is routine. The dosage amount is also readily ascertainable.

[096] Particularly preferred antisense nucleic acid molecules are those that are complementary to a Replikin sequence contained in a mRNA encoding an influenza virus polypeptide, wherein the Replikin sequence comprises from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues. More preferred are antisense nucleic acid molecules that are complementary to a Replikin present in the coding strand of the gene or to the mRNA encoding the influenza virus hemagglutinin protein, wherein the antisense nucleic acid molecule is complementary to a nucleotide sequence encoding a Replikin that has been demonstrated to be conserved over a period of six months to one or more years and/or which are present in a strain of influenza virus shown to have an increase in concentration of R^hki s relative to Replikin concentration in other influenza virus strains. The increase in Replikin concentration preferably occurs over a period of at least six months, preferably about one year, most preferably about two or three years or more.

Similarly, antisense nucleic acid molecules that are complementary to mRNA those that are complementary to a mRNA encoding a Bacillus anthracis polypeptide comprising a repUkin sequence comprising from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten residues from a second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues. More preferred are antisense nucleic acid molecules that are complementary to the coding strand of the gene or to the mRNA encoding the Bacillus anthracis Anthrax Lethal Factor Protein pXOl-107 peptide, wherein the antisense nucleic acid molecule is complementary to a nucleotide sequence encoding the peptide of SEQ ID NO. 91, SEQ ID NO. 92, SEQ ID NO. 93, SEQ ID NO. 94, SEQ ID NO. 95, SEQ ID NO. 96, SEQ ID NO. 97, or SEQ ID NO. 98.

[049] Another preferred set of antisense nucleic acid molecules includes those that are complementary to a mRNA encoding a Small Pox Virus polypeptide comprising a replikin sequence comprising from 7 to about 50 amino acids including (1) at least one lysine residue located six to ten residues from a. second lysine residue; (2) at least one histidine residue; and (3) at least 6% lysine residues. More preferred are antisense nucleic acid molecules that are complementary to the coding strand of the gene or to tT, mR A encoding the Small Pox Virus Surface Antigen S Precursor Protein, where v.. the antisense nucleic acid molecule is complementary to a nucleotide sequence encoding the peptide of SEQ ID NO. 99, SEQ ID NO. 100, SEQ ID NO. 101, SEQ ID NO. 102, or SEQ ID NO. 103.

[097] In'another embodiment of the invention, immune serum containing antibodies to one or more Replikins obtained from an individual exposed to one or more Replikins maybe used to induce passive immunity in another individual or animal. Immune serum may be administered via i.v. to a subject in need of treatment. Passive immunity also can be achieved by injecting a recipient with preformed antibodies to one or more Replikins. Passive immunization may be used to provide immediate protection to individuals who have been exposed to an infectious organism. Administration of immune serum or preformed antibodies is routine and the skilled practitioner can readily ascertain the amount of serum or antibodies needed to achieve the desired effect.

[098] In another aspect of the invention, Replikin structures are used to increase the replication of organisms. The present invention demonstrates that in influenza virus, for example, increased replication associated with epidemics is associated with increased concentration of Replikins. The increase is due to 1) the reappearance of particular replikin structures, which were present in previous years, but which then disappeared for one or more years; and/or 2) by the appearance of new replikin compositions. In addition, in malaria Replikins, repetition of the same R^likin in a single protein occurs.

Thus, the present invention provides methods and compositions for increasing the replication of organisms. For example, the production of crops which are critical to feeding large populations throughout the world, such as rice, for example, can be improved by increasing the concentration (number of Replikdns/100 amino acid residues) of any particular strain of the food crop.

[099] As an example, in the Oryza sativa strain of rice, catalase isolated from immature seeds was observed to contain three different Replikins within the 491 amino acid sequence of the protein. Thus, by using recombinant gene cloning techniques well known in the art, the concentration of Replikin structures in an organism, such as a food crop plant, can be increased, which will promote increased replication of the organism.

[100] The present invention also provides methods for identifying Replikin sequences in an amino acid or nucleic acid sequence. Visual scanning of over four thousand sequences was performed in developing the present 3 -point-recognition methods. However, databanks comprising nucleotide and/or amino acid sequences can also be scanned by computer for the presence of sequences meeting the 3 point recognition requirements.

[101] The three point recognition method may also be modified to identify other useful compounds of covalently linked organic molecules, including other covalently linked amino acids, nucleotides, carbohydrates, lipids or combinations thereof. In this embodiment of the invention a sequence is screened for subsequences containing three or more desired structural characteristics. In the case of screening compounds composed of covalently linked amino acids, lipids or carbohydrates the subsequence of 7 to about 50 covalently linked units should contain (1) at least one first amino acid, carbohydrate or lipid residue located seven to ten residues from a second of the first amino acid, carbohydrate or lipid residue; (2) encoding at least one second amino acid, lipid or carbohydrate residue; and (3) at least 6% of the first atnino acid, carbohydrate or lipid residue. In the case of screening nucleotide sequences, the subsequence of about 21 to about 150 nucleotides should contain (1) at least one codon encoding a first amino acid located within eighteen to thirty nucleotides from a second codon encoding the first amino acid residue; (2) at least one second amino acid residue; and (3) encodes at least 6% of said first amino acid residue.

[102] According to another embodiment of the invention, the methods described herein may be performed by a computer. Figure 6 is a block diagram of a computer available for use with the foregoing embodiments of the present invention.

The computer may include a processor, an input/output device and a memory storing executable program instructions representing the 3-point-recognition methods of the foregoing embodiments. The memory may include a static memory, volatile memory and/or a nonvolatile memory. The static memory conventionally may be a read only memory ("ROM") provided on a magnetic, or an electrical or optical storage medium. The volatile memory conventionally may be a random access memory ("RAM") and maybe integrated as a cache within the processor or provided externally from the processor as a separate integrated circuit. The non-volatile memory may be an electrical, magnetic or optical storage medium.

[103] From a proteomic point of view the construction of a "3-point -recognition" template based on the new glioma peptide sequence led directly to identification of a biology-wide class of proteins having related structures and functions. The operation of the 3-point-recognition method resembles identification by the use of a "keyword"search; but instead of using the exact spelling of the keyword "kagvaflhkk" (SEQ ID NO.: 1) as in a typical sequence homology search, or in the nucleotide specification of an amino acid, an abstraction of the keyword delimited by the "3-point-recognition" parameters is used. This delimited abstraction, although derived from a single relatively short arnino acid sequence leads to identification of a class of proteins with structures that are defined by the same specifications. That particular functions, in this case transformation and replication, in addition to structures, turn out also to be shared by members of the exposed class suggests that these structures and functions are related. Thus, from this newly identified short peptide sequence, a molecular recognition 'language' has been formulated, which previously has not been described. Further, the sharing of immunological specificity by diverse members of the class, as here demonstrated for the cancer Replikins, suggests that B cells and their product antibodies recognize RepliMns by means of a similar recognition language. Since "3-point-recognition" is a proteomic method that specifies a particular class of proteins, using three or more different recognition points for other peptides similarly should provide useful information concerning other proteins classes. Further, the "3-point- recognition" method is applicable to other recognins, for example to the TOLL 'innate' recognition of lipopolyssacharides of organisms.

[104] Several embodiments of the present invention are specifically illustrated and described herein. However, it will be appreciated that modifications and variations of the present invention are encompassed by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention.

EXAMPLE 1 PROCESS FOR EXTRACTION. ISOLATION AND IDENTIFICATION OF REPLIKINS AND THE USE OF REPLI TNS TO TARGET. LABEL OR DESTROY REPLIKTN-CONTAINING ORGANISMS a) Algae

[105] The following algae were collected from Bermuda water sites and either extracted on the same day or frozen at -20 degrees C and extracted the next day. The algae were homogenized in a cold room (at 0 to 5 degrees C) in 1 gram aliquots in neutral buffer, for example 100 cc. of 0.005M phosphate buffer solution, pH 7 ("phosphate buffer") for 15 rninutes in a Waring blender, centrifuged at 3000 rpm, and the supernatant concentrated by perevaporation and dialyzed against phosphate buffer in the cold to produce a volume of approximately 15 ml. The volume of this extract solution was noted and an aliquot taken for protein analysis, and the remainder was fractionated to obtain the protein fraction having a pK range between 1 and 4. The preferred method of fractionation is chromatography as follows:

[106] The extract solution is fractionated in the cold room (4 degrees C) on a DEAE cellulose (Cellex-D) column 2.5x11.0 cm, which has been equilibrated with 0.005M phosphate buffer. Stepwise eluting solvent changes are made with the following solutions: Solution 1- 4.04 g. NaH2P04 and 0.5g NaH2P04 are dissolved in 15 litres of distilled water (0.005 molar, pH 7); Solution 2 - 8.57 g. NaH2P04 is dissolved in 2,480 ml. of distilled water; Solution 3 - 17.1 g. of NaH2P04 is dissolved in 2480 ml of distilled water (0.05 molar, pH 4.7); Solution 4 - 59.65 g. of NaH2P04 is dissolved in 2470 ml distilled water (0.175 molar); Solution 5 - 101.6 g. of NaH2P04 is dissolved in 2455 ml distilled water (PH 4.3); Solution 6 - 340.2 g. of NaH2P04 is dissolved in 2465 of distilled water (1.0 molar, pX-i 4.1); Solution 7 - 283.63 g. of 80% phosphoric acid (H3P04) is made up in 2460 ml of distilled water (1.0 molar, pH 1.0).

[107] The extract solution, in 6 to 10 ml volume, is passed onto the column and overlayed with Solution 1, and a reservoir of 300 ml of Solution 1 is attached and allowed to drip by gravity onto the column. Three ml aliquots of eluant are collected and analyzed for protein content at OD 280 until all of the protein to be removed with Solution 1 has been removed from the column. Solution 2 is then applied to the column, followed in succession by Solutions 3, 4, 5, 6 aid 7 until all of the protein which can, be removed with each Solution is removed from the column. The eluates from Solution 7 are combined, dialyzed against phosphate buffer, the protein content determined of both dialysand and dialyzate, and both analyzed by gel electrophoresis. One or two bands of peptide or protein of molecular weight between 3,000 and 25,000 Daltons are obtained in Solution 7. For example the algae Caulerpa mexicana, Laurencia obtura, Cladophexa prolifera, Sargassum natans, Caulerpa verticillata, Halimeda tuna, and Penicillos capitatus, after extraction and treatment as above, all demonstrated in Solution 7 eluates sharp peptide bands in this molecular weight region with no contaminants. These Solution 7 proteins or their eluted bands are hydrolyzed, and the amino acid composition deterrnined. The peptides so obtained, which have a lysine composition of 6% or greater are Replikin precursors. These R^lilrin peptide precursors are then determined for amino acid sequence and the replikins are deterrnined by hydrolysis and mass spectrometry as detailed in U.S. patent 6,242,578 Bl. Those which fulfill the criteria defined by the " 3-point-recognition" method are identified as Replikins. This procedure can also be applied to obtain yeast, bacterial and any plant Replikins. b) Virus

[108] Using the same extraction and column chromatography separation methods as above in a) for algae, Replikens in virus-infected cells are isolated and identified. c) Tumor cells in vivo and in vitro tissue culture

[109] Using the same extraction and column chromatography separation methods as above in a) for algae, Replikins in tumor cells are isolated and identified. For example, Replikin precursors of Astrocytin isolated from malignant brain tumors, Malignin (Aglyco 10B) isolated from glioblastoma tumor cells in tissue cuOlture, MCF7 mammary carcinoma cells in tissue culture, and P3 J Lymp homa cells in tissue culture each treated as above in a) yielded Replikin precursors with lysine content of 9.1%, 6.7%, 6.7%, and 6.5% respectively. Hydrolysis and mass spectrometry of Aglyco 10B as described in Example 10 U.S. 6,242,578 Bl produced the amino acid sequence, ykagvafihkl ndiide the 16-mer Rephkin.

EXAMPLE 2:

[110] As an example of diagnostic use of Replikins: Aglyco 10B or the 16-mer Repliken may be used as antigen to capture and quantify the amount of its corresponding antibody present in serum for diagnostic purposes are as shown in Figures 2,3,4 and 7 of U.S. 6,242,578 Bl.

[Ill] As an example of the production of agents to attach to Replikins for labeling, nutritional or destructive purposes: Injection of the 16-mer Replikin into rabbits to produce the specific antibody to the 16-mer Replikin is shown in Example 6 and Figures 9A and 9B of U.S. 6,242,578 Bl.

[112] As an example of the use of agents to label Replikins: The use of antibodies to the 16-mer Replikin to label specific cells which contain this Replikin is shown in Figure 5 and Example 6 of U.S. 6,242,578 Bl.

[113] As an example of the use of agents to destroy Replikins: The use of antibodies to the 16-mer Replikin to inhibit or destroy specific cells which contain this Replikin is shown in Figure 6 of U.S. 6,242,578 Bl.

EXAMPLE 3

[114] Analysis of sequence data of isolates of influenza virus hemagglutinin protein or neuraminidase protein for the presence and concentration of Replikins is carried out by visual scanning of sequences or through use of a computer program based on the 3-point recognition system described herein. Isolates of influenza virus are obtained and the amino acid sequence of the influenza hemagglutinin and/or neuraminidase protein is obtained by any art known method, such as by sequencing the hemagglutinin or neurarninidase gene and deriving the protein sequence therefrom. Sequences are scanned for the presence of new Replikins, conservation of Replikins over time and concentration of Replikins in each isolate. Comparison of the Replikin sequences and concentrations to the amino acid sequences obtained from isolates at an earlier time, such as about six months to about three years earlier, provides data that are used to predict the emergence of strains that are most likely to be the cause of influenza in upcoming flu seasons, and that form the basis for seasonal influenza peptide vaccines or nucleic acid based vaccines. Observation of an increase in concentration, particularly a stepwise increase in concentration of Replikins in a given strain of influenza virus for a period of about six months to about three years or more is a predictor of emergence of the strain as a likely cause of influenza epidemic or pandemic in the future.

[115] Peptide vaccines or nucleic acid-based vaccines based on the Replikins observed in the emerging strain are generated. An emerging strain is identified as the strain of influenza virus having the highest increase in concentration of replikin sequences within the hemagglutinin and/or neuraminidase sequence during the time period. Preferably, the peptide or nucleic acid vaccine is based on or includes any Replikin sequences that are observed to be conserved in the emerging strain.

Conserved replikins are preferably those Replikin sequences which are present in the hemagglutinin or neuraminidase protein sequence for about two years and preferably longer. The vaccines may include any combination of Replikin sequences identified in the emerging strain. . 1116] For vaccine production, the Replikin peptide or peptides identified as useful for an effective vaccine are synthesized by any method, including chemical synthesis and molecular biology techniques, including cloning, expression in a host cell and purification therefrom. The peptides are preferably admixed with a pharmaceutically acceptable carrier in an amount determined to induce a therapeutic antibody reaction thereto. Generally, the dosage is about 0.1 μg to about 10 mg. (117] The influenza vaccine is preferably administered to a patient in need thereof prior to the onset of "flu season." Influenza flu season generally occurs in late October and lasts through late April. However, the vaccine may be administered at any time during the year. Preferably, the influenza vaccine is administered once yearly, and is based on Replikin sequences observed to be present, and preferably conserved in the emerging strain of influenza virus. Another preferred Replikin for inclusion in an influenza vaccine is a Replikin demonstrated to have re-emerged in a strain of influenza after an absence of one or more years.

EXAMPLE 4

[118] Analysis of sequence data of isolates of Plasmodium falciparum antigens for the presence and concentration of Replikins is carried out by visual scanning of sequences or through use of a computer program based on the 3-point recognition system described herein. Isolates of Plasmodium falciparum are obtained and the amino acid sequence of the protein is obtained by any art known method, such as by sequencing the gene and deriving the protein sequence therefrom. Sequences are scanned for the presence of Replikins, conservation of Rephkins over time and concentration of Replikins in each isolate. This information provides data that are used to form the basis for anti-malarial peptide vaccines or nucleic acid based vaccines.

[119] Peptide vaccines or nucleic acid-based vaccines based on the Replikins observed in the malaria causing organism are generated. Preferably, the peptide or nucleic acid vaccine is based on or includes any Replikin sequences that are observed to be present on a surface antigen of the organism. The vaccines may include any combination of eplikin sequences identified in the malaria causing strain.

[120] For vaccine production, the Replikin peptide or peptides identified as useful for an effective vaccine are synthesized by any method, including chemical synthesis and molecular biology techniques, including cloning, expression in a host cell and purification therefrom. The peptides are preferably admixed with a pharmaceutically acceptable carrier in an amount determined to induce a therapeutic antibody reaction thereto. Generally, the dosage is about 0.1 μg to about 10 mg.

[121] Then malaria vaccine is preferably aclministered to a patient in need thereof at any time during the year, and particularly prior to travel to a tropical environment. -65- 158109/2 SEQUENCE LISTING <110> BOGOCH, SAMUEL BOGOCH, ELENORE S. <120> REPLIKIN PEPTIDES AND METHODS OF USE <130> 09425-46976 <140> <141> <150> 60/303,396 <151> 2001-07-09 <150> 60/278,761 <151> 2001-03-27 <150> 09/146,755 <151> 1998-09-04 <150> 09/817,144 <151> 2001-03-27 <150> 08/198,139 <151> 1994-02-17 <160> 535 <170> Patentln 2.1 <210> 1 <211> 10 <212> PRT <213> Art ficial Sequence <220> <223> Description of Artificial Sequence: Synthetic glioma rep! kin <400> 1 Lys Ala Gly al Ala Phe Leu His Lys Lys 1 5 10 <210> 2 <211> 13 <212> PRT <213> Saccharomyces cerev siae <400> 2 His Ser lie Lys Arg Glu Leu Gly lie lie Phe Asp Lys 1 5 10 <210> 3 <211> 10 <212> PRT <213> Gem ni vinis virus <400> 3 His Lys Gin Lys lie al Ala Pro val Lys 1. 5 10 <210> 4 <211> 16 <212> PRT <213> unknown organism <220> <223> Description of unknown Organism: v rus recognin <400> 4 Tyr Lys Ala Gly Val Ala Phe Leu His Lys Lys Asn Asp lie Asp Glu 1 5 10 15 <210> 5 <211> 10 <212> PRT <213> Human immunodeficiency virus type 1 <400> 5 Lys Cys Phe Asn Cys Gly Lys Glu Gly His 1 5 10 <210> 6 <211> 11 <212> PRT <213> Human mmunodefic ency virus type 1 <400> 6 Lys Val Tyr Leu Ala Trp Val Pro Ala H s Lys 1 5 10 <210> 7 <211> 10 <212> PRT <213> Human immunodeficiency virus type 2 <400> 7 Lys Cys Trp Asn Cys Gly Lys Glu Gly H s 1 5 10 <210> 8 <211> 11 <212> PRT <213> Maize streak virus <400> 8 Lys Tyr lie Val Cys Ala Arg Glu Ala His Lys 1 5 10 <210> 9 <211> 17 <212> PRT <213> Maize streak virus <400> 9 Lys Glu Lys Lys Pro Ser Lys Asp Glu lie Met Arg Asp lie lie Ser 1 5 10 15 ■ His <210> 10 <211> 9 <212> PRT <213> Staphylococcus aureus -67- 158109/2 <400> 10 Lys Lys Glu Lys Thr Thr His Asn Lys 1 5 <210> 11 <211> 10 <212> PRT <213> Bovine herpesvirus 4 <400> 11 His Lys lie Asn lie Thr Asn Gly Gin Lys 1 5 10 <210> 12 <211> 10 <212> PRT <213> eleagrid herpesvirus 1 <400> 12 His Lys Asp Leu Tyr Arg Leu Leu Met Lys 1 5 10 <210> 13 <211> 15 <212> PRT <213> Unknown organsim <220> <223> Description of Unknown Organism: Virus recognin <400> 13 Lys Phe Arg lie Asn Ala Lys Asn Tyr Phe Leu Thr Tyr Pro His 1 5 10 15 <210> 14 <211> 19 <212> PRT <213> Unknown Organism <220> <223> Description of Unknown Organism: virus recognin <400> 14 Lys Asn Leu Glu Thr Pro val Asn Lys Leu Phe lie Arg lie Cys Arg 1 5 10 15 Glu Phe His <210> 15 <211> 14 <212> PRT <213> Unknown Organism <220> <223> Description of Unknown Organism: Virus recogn <400> 15 His Pro Asn lie Gin Ala Ala Lys Ser Ser Thr Asp val 1 5 10 <210> 16 <211> 19 -68- 158109/2 <212> PRT <213> unknown organism <220> <223> Description of Unknown Organism: irus recognin <400> 16 Lys Ser Ser Thr Asp val Lys Ala Tyr Met Asp Lys Asp Gly Asp val 1 5 10 15 Leu Asp His <210> 17 <211> 21 <212> PRT <213> Unknown organism <220> <223> Description of Unknown organism: virus recognin <400> 17 Lys Ala ser Ala Leu Asn lie Leu Arg Glu Lys Ala Pro Lys Asp Phe 1 5 10 15 Val Leu Gin he His <210> 18 <211> 13 <212> PRT <213> Hepatitis C virus <400> 18 His Tyr Pro Pro Lys Pro Gly Cys lie Val Pro Ala Lys 1 5 10 <210> 19 <211> 4 <212> PRT <213> Homo sapiens <400> 19 Tyr Lys Ala Gly 1 <2l0> 20 <211> 6 <212> PRT <213> Homo sapiens <400> 20 Tyr Lys Ala Gly Val Ala 1 5 <210> 21 <211> 7 <212> PRT <213> Homo sapiens <400> 21 Tyr Lys Ala Gly val Ala Phe 1 5 69 - 158109/2 <210> 22 <211> 7 <212> PRT <213> Homo sapiens <400> 22 Tyr Lys Ala Gly val Ala Phe 1 5 <210> 23 <211> 9 <212> PRT <213> Homo sapiens <400> 23 Ala Gly val Ala Phe H s Lys Lys Asn 1 5 <210> 24 <211> 4 <212> PRT <213> Homo sapiens <400> 24 Gly al Ala Phe 1 <210> 25 <211> 3 <212> PRT <213> Homo sapiens <400> 25 val Ala Phe 1 <210> 26 <211> 7 <212> PRT <213> Homo sapiens <400> 26 val Ala Phe Leu His Lys Lys 1 5 <210> 27 <211> 7 <212> PRT <213> Homo sapiens <400> 27 val Ala Phe Leu His Lys Lys 1 5 <210> 28 <211> 9 <212> PRT <213> Homo sapiens <400> 28 Val Ala Phe Leu His Lys Lys Asn Asp <210> 29 <211> 8 <212> PRT <213> Homo sapiens <400> 29 Val Ala Phe His Lys Lys Asn Asp 1 5 <210> 30 <211> 4 <212> PRT <213> Homo sapiens <400> 30 Ala Phe Leu His 1 <210> 31 <211> 8 <212> PRT <213> Homo sapiens <400> 31 His Lys Lys Asn Asp lie Asp Glu 1 5 <210> 32 <211> 6 <212> PRT <213> Homo sapiens <400> 32 Lys Lys Asn Asp lie Asp 1 5 <210> 33 <211> 6 <212> PRT <213> Homo sapiens <400> 33 Lys Asn Asp lie Asp Glu 1 5 <210> 34 <211> 8 <212> PRT <213> caldophera prolifera <400> 34 Lys Ala Ser Lys Phe Thr Lys His 1 5 <210> 35 <211> 12 <212> PRT <213> isolepis prolifera -71 - 158109/2 <400> 35 Lys Ala Gin Ala Glu Thr Gly Glu lie Lys Gly His 1 5 10 <210> 36 <211> 10 <212> P T <213> Sch zosaccharomyces pombe <400> 36 Lys Ser Phe Lys Tyr Pro Lys Lys His 1 5 <210> 37 <211> 10 <212> PRT <213> Oryza sativa <400> 37 Lys Lys Ala Tyr Gly Asn Glu Leu His Lys 1 5 10 <210> 38 <211> 9 <212> PRT <213> Penicillium marneffei <400> 38 Lys val Asp lie val Thr H s Gin 1 5 <210> 39 <211> 12 <212> PRT <213> Diseula dcstructiva <400> 39 Lys Leu Glu Glu Asp Ala Ala Tyr His Arg Lys Lys 1 5 10 <210> 40 <211> 17 <212> PRT <213> Ophiostoma novo-ulmi <400> 40 Lys Val lie Leu Pro Leu Arg Gly Asn lie Lys Gly lie Phe Phe 1 5 10 15 His <210> 41 <211> 11 <212> PRT <213> Entamoeba invadens <400> 41 Lys Leu lie Leu Lys Gly Asp Leu Asn Lys His 1 5 10 <210> 42 -72- 158109/2 <211> 8 <212> PRT <213> Helicobacter pylori <400> 42 Lys ser val His Ala Phe Leu Lys 1 5 <210> 43 <211> 9 <212> PRT <213> Mycoplasma pulmonis <400>.43 Lys Val His Phe Phe Gin Leu Lys Lys 1 5 <210> 44 <211> 9 <212> PRT <213> Arabidops s thai i ana <400> 44 Lys Asp His Asp Phe Asp Gly Asp Lys 1 5 <210> 45 <211> 11 <212> PRT <213> Arabidopsis thai i ana <400> 45 Lys Met Lys Gly Leu Lys Gin Lys Lys Ala H s 1 5 10 <210> 46 <211> 12 <212> PRT <213> Arabidopsis thai i ana <400> 46 Lys Glu Leu Ser Ser.Thr Thr Gin Glu Lys Ser His 1 5 10 <210> 47 <211> 9 <212> PRT <213> Fel ne immunodeficiency virus <400> 47 His Leu Lys Asp Tyr Lys Leu val Lys 1 5 <210> 48 <211> 7 <212> PRT <213> Rous sarcoma virus <400> 48 Lys Lys Leu Arg H s Glu Lys <210> 49 <211> 7 <212> PRT <213> Avian sarcoma v rus <400> 49 Lys Lys Leu Arg His Asp Lys 1 5 <210> 50 <211> 7 <212> PRT <213> Homo sapiens <400> 50 Lys Lys Leu Arg His Asp Lys 1 5 <210> 51 <211> 7 <212> PRT <213> Avian sarcoma v rus <400> 51 Lys Lys Leu Arg His Glu Lys 1 5 <210> 52 <211> 7 <212> PRT <213> Homo sapiens <400> 52 Lys Lys Leu Arg His Glu Lys 1 5 <210> 53 <211> 8 <212> PRT <213> Homo sapiens <400> 53 Lys Gin Ala His Glu Leu Ala Lys 1 5 <210> 54 <211> 8 <212> PRT <213> Polyama virus <400> 54 Lys Thr His Arg Phe Ser Lys His 1 5 <210> 55 <211> 8 <212> PRT <213> Sindbis virus <400> 55 Lys Asn Leu His Glu Lys lie Lys -74- 158109/2 <210> 56 <211> 9 <212> PRT <213> Human pap lloamavi rus type 71 <400> 56 Lys H s Arg Pro Leu Leu Gin Leu Lys 1 5 <210> 57 <211> 7 <212> PRT <213> Avian encephalomyel tis virus <400> 57 Lys Ser Pro Asn His Val Lys 1 5 <210> 58 <211> 8 <212> PRT <213> Feline sarcoma v rus <400> 58 Lys Asn lie H s Leu Glu Lys Lys 1 5 <210> 59 <211> 8 <212> PRT <213> Homo sapiens <400> 59 Lys Asn lie His Leu Glu Lys Lys 1 5 <210> 60 <211> 10 <212> PRT <213> Polyoma v rus <400> 60 Lys Pro His Leu Ala Gin Ser Leu Glu Lys 1 5 10 <210> 61 <211> 9 <212> PRT <213> Polyoma v rus <400> 61 Lys Gin His Arg Glu Leu Lys Asp Lys 1 5 <210> 62 <211> 9 <212> PRT <213> Polyoma - 75- 158109/2 <400> 62 Lys Gin His Arg Glu Leu Lys Asp Lys 1 5 <210> 63 <211> 12 <212> P T <213> Murine leukemia virus <400> 63 Lys val Pro val Leu lie Ser Pro Thr Leu Lys His 1 5 10 <210> 64 <211 13 <212> PRT <213> Human T-cell lymphotropic v rus type 2 <400> 64 Lys Ser Leu Leu Leu Glu Val Asp Lys Asp lie S 1 5 10 <210> 65 <211> 13 <212> PRT <213> Homo sapiens <400> 65 Lys Ala Gly lie Thr lie Met Val Lys Arg Glu Tyr His 1 5 10 <210> 66 <211> 8 <212> PRT <213> Homo sapiens <400> 66 Lys Ser Gly Lys His Leu Gly Lys 1 5 <210> 67 <211> 9 <212> PRT <213> Homo sapiens <400> 67 Lys Arg Arg Glu Gin Leu Lys His Lys 1 5 <210> 68 <211> 10 <212> PRT <213> Homo sapiens <400> 68 Lys Ser Phe Glu Val lie Lys Val lie His 1 5 10 <210> 69 <211> 8 <212> PRT <213> Homo sapiens <400> 69 Lys Lys Lys His Thr val Lys Lys 1 5 <210> 70 <211> 9 <212> P T <213> Homo sapiens <400> 70 Lys Ala Gin Lys Asp His Leu Ser Lys 1 5 <210> 71 <211> 10 <212> PRT <213> Homo sapiens <400> 71 H s Leu Lys Arg Val Lys Asp Leu Lys Lys 1 5 10 <210> 72 <211> 11 <212> PRT <213> Homo sapiens <400> 72 Lys Tyr Gly Ser Pro Lys His Arg Leu lie Lys 1 5 10 <210> 73 <211> 13 <212> PRT <213> Papilloma virus type 11 <400> 73 Lys Leu Lys His lie Leu Gly Lys Ala Arg Phe lie Lys 1 5 10 <210> 74 <211> 12 <212> PRT <213> Homo sapiens <400> 74 Lys Gly Asp His val Lys His Tyr Lys lie Arg Lys 1 5 10 <210> 75 <211> 13 <212> PRT <213> Homo sapiens <400> 75 Lys Glu Lys Leu Arg Asp Val Met val Asp Arg His Lys 1 5 10 <210> 76 -77- 158109/2 <211> 15 <212> PRT <213> Homo sapiens <400> 76 Lys Leu Gin Ala Arg Gin Gin Gin Leu Leu Lys Lys lie Glu His 1 5 10 15 <210> 77 <211> 14 <212> PRT <213> Homo sapiens <400> 77 Lys Lys Gly Asn Arg al Ser Pro Thr Met Lys Val Thr His 1 5 10 <210> 78 <211> 9 <212> PRT <213> Homo sapiens <400> 78 Lys Glu lie Pro Leu His Phe Arg Lys 1 5 <210> 79 <211> 8 <212> PRT <213> Homo sapiens <400> 79 Lys Lys Lys Pro His lie Lys Lys 1 5 <210> 80 <211> 9 <212> PRT <213> Homo sapiens <400> 80 Lys Thr Arg His Asp Pro Leu Ala Lys 1 5 <210> 81 <211> 10 <212> PRT <213> Homo sapiens <400> 81 Lys His His Pro Lys Asp Asn Leu lie Lys 1 5 10 <210> 82 <211> 10 <212> PRT <213> Homo. sapiens <400> 82 Lys His Lys Arg Lys Lys Phe Arg Gin Lys 1 5 10 - 78 - 158109/2 <210> 83 <211> 10 <212> P T <213> Homo sapiens <400> 83 Lys Ala Gly val Ala Phe Leu His Lys Lys 1 5 - 10 <210> 84 <211> 10 <212> PRT <213> Homo sapiens <400> 84 Lys His Lys Arg Lys Lys Phe Arg Gin Lys 1 5 10 <210> 85 <211> 10 <212 PRT <213> Homo sapiens <400> 85 Lys Lys Lys Ser Lys Lys His Lys Asp Lys 1 5 10 <210> 86 <211> 11 <212> PRT <213> Homo sapiens <400> 86 His Lys Ser Glu Lys Pro Ala Leu Pro Arg Lys 1 5 10 <210> 87 <211> 14 <212> PRT <213> Homo sapiens <400> 87 Lys Lys Lys Lys Pro Ser Arg Leu Lys Gly Asp Asn Glu Lys 1 5 10 <210> 88 <211> 16 <212> PRT <213> Homo sapiens <400> 88 Lys Thr Lys Lys Gly Asn Arg val Ser Pro Thr Met Lys val Thr His 1 5 10 15 <210> 89 <211> 18 <212> PRT <213> Homo sapiens <400> 89 Lys His Lys Glu Lys Met ser Lys Asp Gly Lys Lys Lys Lys Lys Lys 158109/2 1 10 Ser Lys <210> 90 <211> 9 <212> PRT <213> Legionella sp. <400> 90 Lys lie H s Leu lie ser Val Lys Lys 1 5 <210> 91 <211> 10 <212> PRT <213> Bacillus anthracis <400> 91 His val Lys Lys Glu Lys Glu Lys Asn Lys 1 5 .10 <210> 92 <211> 9 <212> PRT <213> Bacillus anthracis <400> 92 Lys His lie val Lys lie Glu Val Lys 1 . 5 <210> 93 <211> 16 <212> PRT <213> Bacillus anthracis <400> 93 „ Lys Lys Lys Lys lie Lys Asp lie Tyr Gly Lys Asp Ala Leu Leu His 1 5 10 15 <210> 94 <211> 8 <212> PRT <213> Bacillus anthracis <400> 94 Lys Trp Glu Lys lie Lys Gin 1 5 <210> 95 <211> 18 <212> PRT <213> Bacillus anth <400> 95 Lys Lys Leu Gin He Pro Pro Pro lie Glu Pro Lys Lys Asp Asp lie 1 5 10 15 lie His <210> 96 158109/2 <211> 31 <212> PRT <213> Bacillus anthracis <400> 96 His Asn Arg Tyr Ala ser Asn lie val Glu Ser Ala Tyr Leu Leu lie 1 5 10 15 Leu Asn Glu Trp Lys Asn Asn lie Gin ser Asp Leu lie Lys Lys 25 30 <210> 97 <211> 24 <212> PRT <213> Bacillus anthracis <400> 97 His Ala val Asp Asp Tyr Ala Gly Tyr Leu Leu Asp Lys Asn Gin Ser 1 5 10 15 Asp Leu val Thr Asn Ser Lys Lys <210> 98 <211> 13 <212> PRT <213> Bacillus anthracis <400> 98 His Ala Glu Arg Leu Lys Val Gin Lys Asn Ala Pro Lys 1 5 10 <210> 99 <211> 10 <212> PRT <213> Variola virus <400> 99 Lys His Tyr Asn Asn lie Thr Trp Tyr Lys 1 5 10 <210> 100 <211> 12 <212> PRT <213> ariola virus <400> 100 Lys Tyr Ser Gin Thr Gly Lys Glu Leu lie lie His 1 5 10 <210> 101 <211> 17 <212> PRT <213> Variola virus <400> 101 His Tyr Asp Asp Val Arg lie Lys Asn Asp lie Val val Ser Arg Cys 1 5 10 . 15 Lys <210> 102 -81 - 158109/2 <211> 11 <212> PRT <213> Variola virus <400 102 His Arg Phe Lys Leu lie Leu Asp Ser Lys lie 1 5 10 <212> PRT <213> Variola virus <400> 103 Lys Glu Arg Gly His Asn Tyr Tyr Phe Glu 1 5 10 <210> 104 <211> 8 <212> PRT <213> Influenza B virus <400> 104 Lys. Ser His Phe Ala Asn Leu 1 5 <210> 105 <211> 11 <212> PRT <213> Influenza B virus <400> 105 Lys Ser His Phe Ala Asn Leu Lys Gly Thr Lys 1 5 10 <210> 106 <211> 19 <212> PRT <213> influenza B virus <400> 106 Lys Ser His Phe Ala Asn Leu Lys Gly Thr Lys Thr Arg Gly Lys Leu 1 5 10 15 Cys Pro Lys <210> 107 <211> 9 <212> PRT <213> influenza B virus <400> 107 His Glu Lys Tyr Gly Gly Leu 1 5 <210> 108 <211> 11 <212> PRT <213> influenza B virus <400> 108 His Glu Lys Tyr Gly Gly Leu Asn Lys Ser Lys -82- 158109/2 <210> 109 <211> 20 <212> PRT <213> Influenza B virus <400> 109 His Glu Lys Tyr Gly Gly Leu Asn Lys Ser Lys Pro Tyr Tyr Thr Gly 1 5 10 15 Glu His Ala Lys <210> 110 <211> 13 <212> PRT <213> influenza B virus <400> 110 His Ala Lys Ala lie Gly Asn Cys Pro lie Trp val Lys 1 5 10 <210> 111 <211> 23 <212> PRT <213> influenza B virus <400> 111 His Ala Lys Ala lie Gly Asn Cys Pro lie Trp val Lys Thr Pro Leu 1 5 10 15 Lys Leu Ala Asn Gly Thr Lys <210> 112 <211> 29 <212> PRT <213> influenza B virus <400> 112 His Ala Lys Ala lie Gly Asri Cys Pro lie Trp al Lys Thr Pro Leu 1 5 10 15 Lys Leu Ala Asn Gly Thr Lys Tyr Arg Pro Pro Ala Lys 25 <210> 113 <211> 32 <212> PRT <213> influenza B virus <400> 113 His Ala Lys Ala lie Gly Asn Cys Pro lie Trp val Lys Thr Pro Leu 1 5 10 15 Lys Leu Ala Asn Gly Thr Lys Tyr Arg Pro Pro Ala Lys Leu Leu Lys 25 30 <210> 114 <211> 13 <212> PRT -83- 158109/2 <213 Influenza B virus <400> 114 His Phe Ala Asn Leu Lys Gly Thr Lys Thr Arg Gly Lys 1 5 10 <210> 115 <211> 17 <212> PRT <213> Influenza B virus <400> 115 His Phe Ala Asn Leu Lys Gly Thr Lys Thr Arg Gly Lys Leu Cys Pro 1 5 10 15 Lys <210> 116 <211> 16 <212> PRT <213> influenza B virus <400> 116 His Ser Asp Asn Glu lie Gin Met Val Lys Leu Tyr Gly Asp Ser Lys 1 5 10 15 <210> 117 <211> 21 <212> PRT <213> influenza B virus <400> 117 His Ser Asp Asn Glu lie Gin Asp Lys Met Val Lys Leu Tyr Gly Asp 1 5 10 15 Ser Lys Pro Gin Lys <210> 118 <211> 19 <212> PRT <213> Influenza B virus <400> 118 His Ser Asp Asn Glu lie Gin Met Val Lys Leu Tyr Gly Asp Ser Lys 1 5 10 15 pro Gin Lys <210> 119 <211> 9 <212> PRT <213> Influenza B virus <220> <221> MOD_RES <222> (2) <223> ala or val <400> 119 Lys Xaa Ser lie Leu His Glu Val Lys 1 5 -84- 158109/2 <210> 120 <211> 15 <212> PRT <213> influenza B virus <400> 120 Lys Cys Thr Gly Thr lie Pro Ser Ala Lys Ala Ser lie Leu His 1 5 10 15 <210> 121 <211> 18 <212> PRT <213> influenza B virus <400> 121 Lys Cys Thr Gly Thr lie Pro Ser Ala Lys Ala Ser lie Leu His Glu 1 5 10 15 val Lys <210> 122 <211> 16 <212> PRT <213> influenza B v rus <400> 122 Lys Tyr Gly Gly Leu Asn Lys ser Lys Pro Tyr Tyr Thr Gly Glu His 1 5 10 15 <210> 123 <211> 26 <212> PRT <213> influenza B vi rus <400> 123 Lys val Trp cys Ala Ser Gly Arg Ser Lys Val lie Lys Gly Ser Leu 1 5 10 15 Pro Leu lie Gly Glu Ala Asp Cys Leu His 25 <210> 124 <211> 10 <212> PRT <213> Influenza B virus <400> 124 Lys Pro Tyr Tyr Thr Gly Glu His Ala Lys 1 5 10 <210> 125 <211> 18 <212> PRT <213> Influenza B virus <400> 125 Lys Cys Met Gly Thr lie Pro Ser Ala Lys Ala Ser lie Leu His Glu 1 5 - 10 15 Val Lys -85- 158109/2 <210> 126 <211> 15 <212> PRT <213> Influenza B virus <400> 126 His Asn val He Asn Ala Glu Lys Ala Pro Gly Gly Pro Tyr Lys 1 5 10 15 <210> 127 <211> 16 <212> PRT <213> Influenza B virus <400> 127 His Ser Asp Asn Glu Thr Gin Met Ala Lys Leu Tyr Gly Asp Ser Lys 1 5 10 15 <210> 128 <211> 18 <212> PRT <213> influenza B virus <400> 128 His Gly Val Ala Val Ala Ala Asp Leu Lys Ser Thr Gin Glu Ala He 1 5 10 15 Asn Lys <210> 129 <211> 29 <212> PRT <213> influenza B virus <400> 129 His Gly Val Ala val Ala Ala Asp Leu Lys Ser Thr Gin Glu Ala lie 1 5 10 15 Asn Lys Asp Thr lie ser Thr Gin Glu Ala lie Asn Lys 25 <210> 130 <211 21 <212> PRT <213> Influenza B v rus <400> 130 Lys Leu Tyr Gly Asp Ser Lys Pro Gin Lys Phe Thr Ser Ser Ala Asn 1 5 10 15 Gly val Thr Thr His <210> 131 <211> 19 <212> PRT <213> Influenza <400> 131 His ser Asp Asn Glu Thr Gin Met Ala Lys Leu Tyr Gly Asp ser Lys 1 5 10 15 Pro Gin Lys -86- 158109/2 <210> 132 <211> 13 <212> PRT <213> influenza B virus <400> 132 His Phe Ala Asn Leu Lys Gly Thr Gin Thr Arg Gly Lys 1 5 10 <210> 133 <211> 12 <212> PRT <213> influenza B v rus <400> 133 Lys Pro Arg Ser Ala Leu Lys cys Lys Gly Phe 1 5 10 <210> 134 <211> 22 <212> PRT <213> Influenza B virus <220> <221> OD_RES <222> (15) <223> gly or ala <400> 134 Lvs Ser Lys Pro Tyr Tyr Thr Gly Glu His Ala Lys Ala lie Xaa Asn 1 5 10 15 cys Pro lie Trp val Lys <210> 135 <211> 16 <212> PRT <213> influenza virus <220> <221> OD_RES <222> (3) <223> val or ile <220> <221> MOD_RES <222> C13) <223> arg or lys <220> <221> MOD_RES <222> (14) <223> ser or thr <220> <221> OD_RES <222> (15) <223> thr or ala <400> 135 His Pro xaa Thr lie Gly Glu Cys Pro Lys Tyr Val Xaa Xaa Xaa Lys -87- 158109/2 15 <210> 136 <211> 21 <212> P T <213> influenza virus <220> <221> MOD_RES <222> (10) <223> glu or gly <220> <221> MOD_RES <222> (13) <223> lys or arg <220> <221> MOD_RES <222> (14) <223> asn or ser <220> <221> MOD_RES <222> (17) <223> lys or arg <400> 136 , His Asp Ser Asn Val Lys Asn Leu Tyr Xaa Lys val Xaa Xaa Gin Leu 1 5 10 15 Xaa Asn Asn Ala Lys <210> 137 <211> 17 <212> PRT <213> Influenza virus <220> <221> OD_RES <222> (10) <223> glu or gly <220> <221> OD_RES <222> (13) <223> lys or arg <220> <221> MOD_RES <222> (14) <223> asn or ser <400> 137 His Asp Ser Asn val Lys Asn Leu Tyr xaa Lys Val Xaa xaa Gin Leu 1 5 10 15 Lys <210> 138 <211> 36 <212> PRT <213> influenza virus -88- 158109/2 <220> <221> MOD_ ES <222> (4).. (5) <223> asn or asp <220> <221> MOD_RES <222> (6) <223> ala, thr or glu <220> <221> MOD_RES <222> (12) <223> arg or lys <220> <221> MOD_RES <222> (31) <223> glu or lys <400> 138 . , His Lys cys xaa Xaa Xaa cys Met Glu Ser val Xaa Asn Gly Thr Tyr 1 5 . 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Xaa lie 25 30 Asp Gly Val Lys <210> 139 <211> 26 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (4).. (5) <223> asn or asp <220> <221> MOD_RES <222> (6) <223> ala, thr or glu <220> <221> MOD_RES <222> (12) <223> arg or lys <400> 139 His Lys Cys Xaa Xaa Xaa Cys Met Glu Ser Val Xaa Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys 25 <210> 140 <211> 50 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (4) <223> glu or gly -89- 158109/1 <220> <221> MOD_RES <222> (21) <223> asp or asn <400> 140 His Gin Asn Xaa Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala He xaa Gly He Thr Asn Lys val Asn Ser val He Glu 25 30 Lys Met Asn Thr Gin Phe Thr Ala val Gly Lys Glu Phe Asn Lys Leu 40 45 Glu Lys 50 <210> 141 <211> 33 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (4) <223> glu or gly <220> <221> MOD_RES <222> (21) <223> asp or asn <400> 141 ■ His Gin Asn Xaa Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys ser Thr 1 5 10 15 Gin Asn Ala He Xaa Gly He Thr Asn Lys Val Asn ser Val He Glu 25 30 Lys <210> 142 <211> 26 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (4) <223> glu or gly <220> <221> MOD_RES <222> (21) <223> asp or asn <400> 142 His Gin Asn Xaa Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys ser Thr 1 5 10 15 Gin Asn Ala lie Xaa Gly lie Thr Asn Lys 25 -90- 158109/1 <210> 143 <211> 14 <212> P T <213> Influenza v rus <400> 143 -Lys Phe Glu lie Phe Pro Lys Thr Ser Ser Trp Pro Asn His 1 5 10 <210> 144 <211> 27 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (3) <223> asn, ser or thr <220> <221> MOD_RES <222> (9) <223> asn or ser <220> <221> MOD_RES <222> (13) <223> val or thr <400> 144 Lys Gly xaa Ser Tyr Pro Lys Leu xaa Lys Ser Tyr Xaa Asn Asn Lys 1 5 10 15 Gly Lys Glu Val Leu Val Leu Trp Gly Val H s 25 <210> 145 <211> 18 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (4) <223> val or thr <400> 145 Lys ser Tyr Xaa Asn Asn Lys Gly Lys Glu val Leu val Leu Trp Gly 1 5 10 15 Val His <210> 146 <211> 36 <212> PRT <213> influenza virus <400> 146 , His Lys cys Asn Asn Glu Cys Met Glu Ser val Lys Asn Gly Thr Tyr 1 5 10 15 · Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn Arg Glu Lys lie 25 30 Asp Gly Val Lys - 91 - 158109/1 <210> 147 <211> 26 <212> P T <213> Influenza vi rus <400> 147 His Lys Cys Asn Asn Glu Cys Met Glu Ser val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys 25 <210> 148 <211> 20 <212> PRT <213> Influenza virus <400> 148 His Lys Cys Asn Asn Glu Cys Met Glu Ser Val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys <210> 149 <211> 12 <212> PRT <213> influenza virus <400> 149 His Lys Cys Asn Asn Glu Cys Met Glu Ser Val 1 5 10 <210> 150 <211> 34 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (9) <223> lys or arg <220> <221> MOD_RES <222> (16) <223> glu or gly <400> 150 , His Asn Gly Lys Ser Ser Phe Tyr Xaa Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys ser Tyr Val Asn Asn Lys 25 30 Glu Lys <210> 151 <211> 32 <212> PRT <213> Influenza virus - 92 - 158109/1 <220> <221> MOD_RES <222> (9) <223> lys or arg <220> <221> MOD_RES <222> (16) <223> glu or gly <400> 151 His Asn Gly Lys Ser ser Phe Tyr Xaa Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr val Asn Asn Lys 25 30 <210> 152 <211> 26 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (9) <223> lys or arg <220> <221> MOD_RES <222> (16) <223> glu or gly <400> 152 . v His Asn Gly Lys Ser Ser Phe Tyr xaa Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys 25 <210> 153 <211> 17 <212> PRT <213> influenza v rus <220> <221> OD_RES <222> (9) <223> lys or arg <220> <221> MOD_RES <222> (16) <223> glu or gly <400> 153 , v His Asn Gly Lys Ser Ser Phe Tyr xaa Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys <210> 154 <211> 40 <212> PRT <213> influenza v rus -93- 158109/1 <400> 154 ■ Lys Ser ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly 1 5 10 15 Leu Tyr Pro Asn Leu Ser Lys ser Tyr Val Asn Asn Lys Glu Lys Glu 25 30 val Leu val Leu Trp Gly val His 40 <210> 155 <211> 35 <212> P T <213> influenza v rus <400> 155 Lys Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly Leu Tyr Pro Asn Leu 1 5 10 15 Ser Lys Ser Tyr Val Asn Asn Lys Glu Lys Glu val Leu Val Leu Trp 25 30 Gly val His <210> 156 <211> 27 <212> PRT <213> Influenza virus <400> 156 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr val Asn Asn Lys 1 5 10 15 Glu Lys Glu Val Leu val Leu Trp Gly Val His 25 <210> 157 <211> 18 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (4) <223> val or a! a <220> <221> MOD_RES <222> (12) <223> lys or not present <220> <221> MOD_RES <222> (13) <223> val or not present <400> 157 Lys Ser Tyr Xaa Asn Asn Lys Glu Lys Glu Val xaa xaa Leu Trp Gly 1 5 10 15 Val Hi s <210> 158 <211> 12 <212> PRT <213> influenza virus <400> 158 Lys Glu Ser ser Trp Pro Asn His Thr val Thr 1 ' 5 10 <210> 159 <211> 44 <212> PRT <213> influenza virus <220> <221> OD_RES <222> (4) <223> thr or asn <400> 159 His Glu Thr xaa Lys Gly val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 10 15 Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Val Lys Lys Glu Asn Ser 25 30 Tyr Pro Lys Leu Ser Lys Ser Tyr Val Asn Asn Lys 40 <210> 160 <211> 38 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (4) <223> thr or asn <400> 160 His Glu Thr Xaa Lys Gly Val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 10 15 Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Val Lys Lys Glu Asn ser 25 30 Tyr Pro Lys Leu Ser Lys <210> 161 <211> 22 <212> PRT <213> Influenza vi rus <400> 161 Lys Phe Glu lie Phe Pro Lys Thr Ser Ser Trp Pro Asn Glu al Leu 1 5 10 15 Val Leu Trp Gly Val H s <210> 162 <211> 8 <212> PRT <213> Influenza virus <400> 162 Lys Glu Arg ser Trp Pro Lys 1 5 <210> 163 <211> 21 <212> P T <213> Influenza v rus <400> 163 Lys Leu Ser Lys Ser Tyr val Asn Asn Lys Glu Lys Glu Val Leu 1 5 10 15 Leu Trp Gin val His <210> 164 <211> 15 <212> PRT <213> influenza virus <400> 164 Lys Asn Asn Lys Glu Lys Glu Val Leu val Leu Trp Gin val His 1 5 10 15 <210> 165 <211> 34 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> C2) <223> lys or asn <220> <221> MOD_RES <222> (3) <223> gly or gin <220> <221> OD_RES <222> (9 <223> arg or lys <220> <221> OD_RES <222> (20) <223> lys or ser <220> <221> OD_RES <222> (23) <223> asn or thr <400> 165 His Xaa xaa Lys Ser Ser Phe Tyr xaa Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Asn Gly Xaa Tyr Pro Xaa Leu ser Lys Ser Tyr Ala Asn Asn Lys 25 30 Glu Lys -96- 158109/1 <210> 166 <211> 17 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (2) <223> lys or asn <220> <221> MOD_RES <222> (3) <223> gly or gin <220> <221> MOD_RES <222> (9) <223> arg or lys <400> 166 His xaa xaa Lys Ser Ser Phe Tyr xaa Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys <210> 167 <2ll> 9 <212> PRT <213> influenza v rus <400> 167 His Ala Lys Lys Ser Ser Phe Tyr 1 5 <210> 168 <211> 11 <212> PRT <213> Influenza v rus <400> 168 His Asn Gly Lys Leu Cys Arg Leu Lys Gly Lys 1 5 10 <210> 169 <211> 9 <212> PRT <213> Influenza v rus <220> <221> MOD_RES <222> C7) <223> gin or gly <400> 169 His Tyr Lys Leu Asn Asn Xaa Lys Lys 1 5 <210> 170 <211> 25 <212> PRT <213> Influenza v rus -97- 158109/1 <400> 170 His Asp lie Tyr Arg Asp Glu Ala lie Asn Asn Arg Phe Gin lie Gin 1 P 5 10 15 Gly val Lys Leu Thr Gin Gly Tyr Lys 25 <210> 171 <211> 11 <212> PRT <213> influenza v rus <400> 171 Lys Gly Asn Gly Cys Phe Glu lie Phe His Lys 1 5 10 <210> 172 <211> 18 <212> PRT <213> Influenza virus <400> 172 Lys Leu Asn Arg Leu lie Glu Lys Thr Asn Asp Lys Tyr His Gin lie 1 5 10 15 Glu Lys <210> 173 <211> 14 <212> PRT <213> Influenza virus <400> 173 Lys Leu Asn Arg Leu lie Glu Lys Thr Asn Asp Lys Tyr 1 5 10 <210> 174 <211> 13 <212> PRT <213> Influenza virus <400> 174 Lys Cys His Thr Asp Lys Gly Ser Leu ser Thr Thr Lys 1 5 10 <210> 175 <211> 16 <212> PRT <213> Influenza virus <400> 175.

Lys lie Asn Asn Gly Asp Tyr Ala Lys Leu Tyr lie Trp Gly val His 1 5 10 15 <210> 176 <211> 17 <212> PRT <213> Influenza <400> 176 His Asn Gly Lys Leu Cys Arg Lys Gly lie Ala Pro Leu Gin Leu - 1 5 10 15 Lys <210> 177 <211> 38 <212> PRT <213> Influenza v rus <400> 177 ' ' His Glu Thr Asn Arg Gin val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 . 5 10 15 Asn Ser Phe Phe Arg Asn Leu lie Trp Leu Val Lys Lys Glu Ser ser 20 25 30 Tyr Pro Lys Leu Ser Lys <210> 178 <211> 35 <212> PRT <213> Influenza virus <400> 178 . . . His Glu Thr Asn Arg Gin val Thr Ala Ala Cys Pro Tyr Ala Gly Ala 1 5 10 15 Asn Ser Phe Phe Arg Asn Leu lie Trp Leu Val Lys Lys Glu Ser Ser 20 25 30 Tyr Pro Lys <210> 179 <211> 31 <212> PRT <213> Influenza virus <400> 179 His Pro Pro Thr Ser Thr Asp Gin Gin Ser Leu Tyr Gin Asn Ala Asp 1 5 10 15 Ala Tyr lie Phe val Gly Ser Ser Lys Tyr Asn Arg Lys Phe Lys 25 30 <210> 180 <211> 35 <212> PRT <213> Influenza vi rus <400> 180 His Pro Pro Thr Ser Thr Asp Gin Gin Ser Leu Tyr Gin Asn Ala Asp 1 5 10 15 Ala Tyr lie Phe Val Gly Ser Ser Lys Tyr Asn Arg Lys Phe Lys Pro 20 25 30 Glu l e Ala <210> 181 <211> 25 -99- 158109/1 <212> PRT <213> influenza virus <400> 181 .

His As lie Tyr Arg Asp Glu Ala lie Asn Asn Arg Phe Gin He G n 1 5 10 15 Gly Val Lys lie Thr Gin Gly Tyr Lys 25 <210> 182 <211> 43 <212> PRT <213> Influenza virus <400> 182 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asp Gly lie Thr Asn Lys Val Asn Ser Val lie Glu 25 30 Lys Met Asn Thr Gin Phe Thr Ala Val Gly Lys 40 <210> 183 <211> 33 <212> PRT <213> influenza virus <400> 183 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asp Gly lie Thr Asn Lys val Asn Ser Val lie Glu . 25 30 Lys <210> 184 <211> 50 <212> PRT <213> influenza virus <400> 184 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys val Asn Ser Val He Glu 25 30 Lys Met Asn Thr Gin Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu 40 45 Glu Lys 50 <210> 185 <211> 18 <212> PRT <213> influenza virus <400> 185 ' His Asn Gly Lys Leu cys Arg Leu Lys Gly lie Ala Pro Leu Gin Leu - 100- 158109/1 1 10 15 Gly Lys <210> 186 <211> 12 <212> P T <213> influenza v rus <400> 186 His Lys Cys Asn Asn Glu Cys Met Glu ser val 1 5 10 <210> 187 <211> 14 <212> PRT <213> influenza virus <400 187 Lys Phe Glu lie Phe Pro Lys Ala Ser ser Trp Pro Asn His 1 5 10 <210> 188 <211> 21 <212> PRT <213> influenza virus <400> 188 His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys Val Arg Ser Gin Leu 1 5 10 15 Arg Asn Asn Ala Lys <210> 189 <211> 22 <212> PRT <213> influenza v rus <400> 189 Lys val Asn ser val lie Lys Lys Met Asn Thr Gin Phe Ala Ala val 1 5 10 15 Gly Lys Glu Phe Asn His <210> 190 <211> 8 <212> PRT <213 influenza virus <400> 190 Lys His Asn Gly Lys Leu Cys Lys 1. 5 <210> 191 <211> 28 <212> PRT <213> influenza vi rus <400> 191 .

Lys Lys Gly Thr Ser Tyr Pro Lys Leu Ser Lys ser Tyr Thr HTS Asn - 101 - 158109/1 1 5 10 Lys Gly Lys Glu Val Leu Val Leu Trp Gly val 25 <210> 192 ' <211> 27 <212> PRT <213> Influenza v rus <400> 192 Lys Gly Thr Ser Tyr Pro Lys Leu Ser Lys Ser Tyr Thr His Asn Lys 1 - 5 10 15 Gly Lys Glu val Leu val Leu Trp Gly val H s 25 <210> 193 <211> 21 <212> PRT <213> influenza virus <400> 193 Lys Leu Ser Lys Ser Tyr Thr His Asn Lys Gly Lys Glu Val Leu Val 1 5 10 15 Leu Trp Gly Val His ■' <210> 194 <211> 18 <212> PRT <213> influenza virus <400> 194 Lys Ser Tyr Thr His Asn Lys Gly Lys Glu Val Leu val Leu Trp Gly 1 5 10 15 Val His <210> 195 <211> 10 <212> PRT <213> influenza virus <400> 195 Lys Gly Val Thr Ala Ser Cys Ser His Lys 1 5 10 <210> 196 <211> 34 <212> PRT <213> Influenza virus <400> 196 Lys Gly Val Thr Ala Ser Cys Ser His Lys Gly Arg ser Ser Phe Tyr 1 5 10 15 Arg Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly Leu Tyr Pro Asn Leu 25 30 Ser Lys - 102- 158109/1 <210> 197 <211> 27 <212> PRT <213> influenza v rus <400> 197 Lys Gly Asn Ser Tyr Pro Lys Leu Ser Lys Ser Tyr val Asn Asn 1 5 10 15 Glu Lys Glu Val Leu Val Leu Trp Gly He His 25 <210> 198 <211> 8 <212> PRT <213> Influenza v rus <400> 198 Lys Glu Phe Asn His Leu Glu 1 5 <210> 199 <211> 39 <212> PRT <213> Influenza virus <400> 199 His Pro Pro Thr Ser Thr Asp Gin Gin Ser Leu Tyr Gin Asn Ala Asp 1 5 10 15 Ala Tyr Val Phe Val Gly Ser Ser Lys Tyr Asn Lys Lys Phe Lys Pro 25 30 Glu lie Ala Thr Arg Pro Lys <210> 200 <211> 31 <212> PRT <213> Influenza v rus <400> 200 His Pro Pro Thr Ser Thr Asp Gin Gin ser Leu Tyr Gin Asn Ala Asp 1 5 10 15 Ala Tyr val Phe Val Gly Ser Ser Lys Tyr Asn Lys Lys Phe Lys 25 30 <210> 201 <211> 31 <212> PRT <213> Influenza virus <400> 201 His Glu Gly Lys Ser ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Glu Gly Ser Tyr Pro Lys Leu Lys Asn ser Tyr val Asn Lys 25 30' <210> 202 <211>- 23 - 103- 158109/1 <212> P T <213> Influenza v rus <400> 202 His Glu Gly Lys Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Glu Gly Ser Tyr Pro Lys <210> 203 <211> 26 <212> PRT <213> Influenza virus <400> 203 His Lys cys Asp Asn Glu Cys Met Glu Ser Val Arg Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys 25 <210> 204 <211> 12 <212> PRT <213> influenza v rus <400> 204 Lys Glu ser Ser Trp Pro Asn His Thr val Thr Lys 1 5 10 <210> 205 <211> 35 <212> PRT <213> Influenza virus <400> 205 Lys Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly Leu Tyr Pro Asn Leu 1 5 10 15 Ser Lys ser Tyr Val Asn Asn Lys Glu Lys Glu lie Leu Val Leu Trp 25 30 Gly val His <210> 206 <211> 27 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (9) <223> lys or met <220> <221> MOD_RES <222> (10) <223> asn or not present <220> <221> MOD_RES <222 (16) <223> glu or gly <220> <221> OD_RES <222> (17) <223> not present or lys <400> 206 His Asn Gly Lys Ser Ser Phe Tyr Xaa Xaa Leu Leu Trp Leu Thr Xaa 1 5 10 15 Xaa Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys 25 <210> 207 <211> 17 <212> PRT <213> influenza virus <400> 207 , His Asn Gly Lys ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys <210> 208 <211> 55 <212> PRT <213> influenza virus <400> 208 His Thr Val Thr Lys Gly val Thr Ala Ser Cys ser His Asn Gly Lys 1 5 10 15 Ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr Glu Lys Asn Gly Leu 25 30 Tyr Pro Asn Leu ser Lys Ser Tyr al Asn Asn Lys Glu Lys Glu val 35 40 45 Leu Val Leu Trp Gly Val H s 50 55 <210> 209 <211> 38 <212> PRT <213> influenza virus <220> <221> OD_RES <222> (5) <223> lys or gly <220> <221> MOD_RES <222> (8) <223> thr or ser <220> <221> MOD_RES <222> (21) <223> lys or met <220>_ <221> OD_RES - 105- 158109/1 <222> (22) <223> asn or not present <220> <221> MOD_ ES <222> (28) <223> glu or gly <220> <221> MOD_RES <222> (30) <223> asn present or not or lys <400> 209 His Thr val Thr Xaa Gly val xaa Ala ser Cys ser His Asn Gly Lys 1 5 10 15 ser Ser Phe Tyr xaa Xaa Leu Leu Trp Leu Thr Xaa Lys Xaa Gly Leu 25 30 Tyr Pro Asn Leu ser Lys <210> 210 <211> 29 <212> PRT <213> influenza virus <400> 210 . n His Thr Val Thr Lys Gly val Thr Ala Ser Cys Ser His Asn Gly Lys 1 5 10 15 Ser Ser Phe Tyr Lys Asn Leu Leu Trp Leu Thr Glu Lys 25 <210> 211 <211> 48 <212> PRT <213> Influenza virus <400> 211 Lys Tyr Val Arg Ser Thr Lys Leu Arg Met val Thr Gly Leu Arg Asn 1 5 . 10 15 lie Pro Ser lie Gin Ser Arg Gly Leu Phe Gly Ala lie Ala Gly Phe 25 30 lie Glu Gly Gly Trp Thr Gly Met He Asp Gly Trp Tyr Gly Tyr His 40 45 <210> 212 <211> 43 <212> PRT <213> influenza virus <400> 212 .

H 5 Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys val Asn ser lie lie Glu 25 30 Lys Met Asn Thr Gin Phe Thr Ala val Gly Lys 40 - 106- 158109/1 <210> 213 <211> 33 <212> P T <213> Influenza virus <400> 213 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys val Asn Ser lie lie Glu 25 30 Lys <210> 214 <211> 26 <212> PRT <213> influenza virus <400> 214 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys 25 <210> 215 <211> 23 <212> PRT <213> influenza virus <400> 215 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp lie val Lys 1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys <210> 216 <211> 26 <212> PRT <213> influenza virus <400> 216 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp lie Val Lys 1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys 25 <210> 217 <211> 32 <212> PRT <213> influenza virus <400> 217 His Ser Gly Ala Arg Ser Phe Tyr Arg Asn Leu Leu Trp l e val Lys 1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys Ser Tyr Thr Asn Asp Lys 25 30 - - <210> 218 <211> 34 <212> PRT <213> influenza virus <400> 218 His Ser Gly Ala Arg Ser Phe Tyr. Arg Asn Leu Leu Trp lie Val Lys .1 5 10 15 Lys Gly Asn Ser Tyr Pro Lys Leu Asn Lys Ser Tyr Thr Asn Asp Lys 25 30 Gly Lys <210> 219 <211> 16 <212> PRT <213> influenza v rus <400> 219 His Thr val ser Lys Gly Val Thr Thr Ser Cys Ser His Asn Gly Lys 1 5 10 15 <210> 220 <211> 12 <212> PRT <213> influenza virus <400> 220 Lys Ala Thr Ser Trp Pro Asn His Glu Thr Thr Lys 1 5 10 <210> 221 <211> 12 <212> PRT <213> influenza virus <400> 221 Lys Gin Val Thr Thr Ser Cys Ser His Asn Gin 1 5 10 <210> 222 <211> 27 <212> PRT <213> influenza virus <400> 222 Lys Gly Asn ser Tyr Pro Lys Leu Asn Lys Ser Tyr Thr Asn Asp- Lys 1 5 10 15 Gly Lys Glu val Leu val lie Trp Gly val His 25 <210> 223 <211> 21 <212> PRT <213> Influenza virus <400> 223 Lys Leu Asn Lys ser Tyr Thr Asn Asp Lys Gly Lys Glu Val Leu 1 5. 10 . .. 15 ΠΤΤΤΓ p-Giy- va-l- H t: - 108 - 158109/1 <210> 224 <211> 18 <212> PRT <213> influenza v rus <400> 224 Lys Ser Tyr Thr Asn Asp Lys Gly Lys Glu val Leu val lie Trp Gly 1 5 10 15 val His <210> 225 <211> 35 <212> PRT <213> Influenza v rus <220> <221> OD_RES <222> (16) <223> glu or gin <220> <221> MOD_RES <222> (29) <223> val or ala <400> 225 His Asn Gin Lys Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Xaa 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Xaa Ala Asn Asn 25 30 Lys Glu Lys <210> 226 <211> 16 <212> PRT <213> Influenza virus <400> 226 His Pro lie Thr lie Gly Glu Cys Pro Lys Tyr Val Arg Ser Ala Lys 1 5 10 15 <210> 227 <211 43 <212> PRT <213> Influenza v rus <400> 227 His Gin Asn Glu Gin Gly Ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys Val Asn ser Val lie Glu 25 30 Lys Met Asn Thr Gin Phe Thr Ala Val Gly Lys 40 <210> 228 - 109 - 158109/1 <211> 33 <212> P T <213> influenza virus <400> 228 n , His Gin Asn Glu Gin Gly ser Gly Tyr Ala Ala Asp Gin Lys Ser Thr 1 5 10 15 Gin Asn Ala lie Asn Gly lie Thr Asn Lys val Asn Ser Val lie Glu 25 30 Lys <210> 229 <211> 34 <212> PRT <213> influenza virus <400> 229 , His Asn Gly Lys Ser Ser Phe Tyr Arg Asn Leu Leu Trp Leu Thr Glu 1 5 10 15 Lys Asn Gly Leu Tyr Pro Asn Leu Ser Lys Ser Tyr Val Asn Asn Lys 25 30 Glu Lys <210> 230 <211> 11 <212> PRT <213> Influenza v rus <400> 230 Lys His Phe Glu Lys val Lys lie Leu Pro Lys 1 5 10 <210> 231 <211> 14 <212> PRT <213> influenza virus <400> 231 Lys His Leu Leu Ser Ser Val Lys His Phe Glu Lys Val Lys 1 5 10 <210> 232 <211> 13 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (3) <223> lys, gin or met <220> <221> MOD_RES <222> C4) <223> asp or asn <400> 232 His Ala Xaa Xaa lle Leu Glu Lys Thr His Asn Gly Lys 1 5 10 - 110- 158109/1 <210> 233 <211> 16 <212> PRT <213> influenza v rus <220> <221> MOD_RES <222> (3) <223> lys, gin or met <220> <221> OD_RES <222> (4) <223> asp or asn <220> <221> MOD_RE5 <222> (16) <223> lys or arg <400> 233 His Ala Xaa Xaa lie Leu Glu Lys Thr His Asn Gly Lys Leu Cys Xaa 1 5 10 15 <210> 234 <211> 19 <212> PRT <213> Influenza virus <400> 234 His Asn Val His Pro Leu Thr lie Gly Glu Cys Pro Lys Tyr Val 1 5 10 15 Ser Glu Lys <210> 235 <211> 16 <212> PRT <213> Influenza v rus <400> 235 His Pro Leu Thr He Gly Glu Cys Pro Lys Tyr Val Lys Ser Glu Lys 1 5 10 15 <210> 236 <211> 18 <212> PRT <213> Influenza virus <400> 236 n Lys His Leu Leu Ser Ser Val Lys His Phe Glu Lys val Lys He Leu 1 5 10 15 Pro Lys <210> 237 <211> 38 <212> PRT <213> Influenza virus <400> 237 Lys Arq Gin Ser Ser Gly lie Met Lys Thr Glu Gly Thr Leu Glu Asn 1 5" 10 1-5 - Ill - 158109/1 Cys Glu Thr Lys Cys Gin Thr Pro Leu Gly Ala lie Asn Thr Thr Leu 25 30 Pro Phe His Asn val <210> 238 <211> 27 <212> PRT <213> influenza v rus <220> <221> MOD_RES <222> (7) <223> val or ile <220> <221> MOD_RES <222> (10) <223> gly or arg <220> <221> MOD_RES <222> C26) <223> val or ile <400> 238 Lys Gly Ser Asn Tyr Pro Xaa Ala Lys xaa Ser Tyr Asn Asn Thr Ser 1 5 10 15 Gly Glu Gin Met Leu Ile Ile Trp Gin Xaa His 25 <210> 239 <211> 36 <212> PRT <213> influenza v rus <400> 239 His Thr Thr Leu Gly Gin Ser Arg Ala Cys Ala val Ser Gly Asn Pro 1 5 10 15 Ser Phe Phe Arg Asn Met val Trp Leu Thr Glu Lys Gly Ser Asn Tyr 25 30 Pro val Ala Lys <210> 240 <211> 7 <212> PRT <213> Influenza virus <400> 240 Lys His Phe Glu Lys val 1 5 <210> 241 <211> 38 <212> PRT <213> influenza virus <400> 241 - 112- 158109/1 Lys lie Ser Lys Arg Gly Ser ser Gly lie Met Lys Thr Glu Gly Thr 1 5 10 15 Leu Glu Asn Cys Glu Thr Lys cys Gin Thr Pro Leu Gly Ala He Asn 25 30 Thr Thr Leu Pro Phe His <210> 242 <211> 35 <212> PRT <213> influenza virus <400> 242 Lys Arg Gly Ser Ser Gly lie Met Lys Thr Glu Gly Thr Leu Glu Asn 1 5 10 15 Cys Glu Thr Lys Cys Gin Thr Pro Leu Gly Ala lie Asn Thr Thr Leu 25 30 pro Phe His <210> 243 <211> 27 <212> PRT <213> influenza virus <400> 243 Lys Thr Glu Gly Thr Leu Glu Asn Cys Glu Thr Lys Cys Gin Thr Pro 1 5 10 15 Leu Gly Ala lie Asn Thr Thr Leu Pro Phe His 25 <210> 244 <211> 38 <212> PRT <213> Influenza v rus <400> 244 Lys lie Ser Lys Arg Gly ser ser Gly lie Met Lys Thr Glu Gly Thr 1 5 10 15 Leu Glu Asn Cys Glu Thr Lys Cys Gin Thr Pro Leu Gly Ala lie Asn 25 30 Thr Thr Leu Pro Phe His <210> 245 <211> 30 <212> PRT <213> Influenza <220> <221> MOD_RES <222> (29) <223> val or ile <400> 245 Lys Thr Glu Gly Thr Leu Glu Asn Cys Glu Thr Lys Cys Gin Thr Pro 1 5 10 15 - 113- 158109/1 Leu Gly Ala lie Asn Thr Thr Leu Pro Phe His Asn xaa His 25 30 <210> 246 <211> 38 <212> P T <213> Influenza virus <400> 246 Lys lie Ser Lys Arg Gly Ser Ser Gly lie Met Lys Thr Glu Gly Thr 1 5 10 15 Leu Glu Asn Cys Glu Thr Lys Cys Gin Thr Pro Leu Gly Ala lie Asn 25 30 Thr Thr Leu Pro Phe His <210> 247 <211> 27 <212> PRT <213> Influenza virus <220> <221> MOD_RES <222> (2) <223> glu or gly <400> 247 Lys Xaa Ser Asn Tyr Pro val Ala Lys Gly ser Tyr Asn Asn Thr Ser 1 5 10 15 Gly Glu Gin Met Leu lie lie Trp Gly Val His 25 <210> 248 <211> 16 <212> PRT <213> influenza v rus <400> 248 His Pro Leu Thr lie Gly Glu Cys Pro Lys Tyr Val Lys Ser Glu Lys 1 5 10 15 <210> 249 <211> 16 <212> PRT <213> Influenza virus <400> 249 Lys Cys Gin Thr Pro Leu Gly Ala lie Lys Thr Thr Leu Pro Phe His 1 5 10 15 <210> 250 <211> 58 <212> PRT <213> Influenza <220> <221> MOD_RES <222> (21) <223> p he b r i 1 e - 114- 158109/1 <220> <221> MOD_RES <222> (47) <223> asn or ser <400> 250 His His Ser Asn Asp Gin Gly Ser Gly Tyr Ala Ala Asp Lys Glu ser 1 5 10 15 Thr Gin Lys Ala xaa Asp Gly lie Thr Asn Lys Val Asn Ser val lie 25 30 Glu Lys Met Asn Thr Gin Phe Glu Ala Val Gly Lys Leu Phe Xaa Asn 40 45 Leu Glu Lys Leu Glu Asn Leu Asn Lys Lys 50 55 <210> 251 <211> 57 <212> PRT <213> Influenza v rus <220> <221> OD_RES <222> (20) <223> phe or ile <220> <221> MOD_RES <222> (46) <223> asn or ser <400> 251 His Ser Asn Asp Gin Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr 1 5 10 15 Gin Lys Ala Xaa Asp Gly Ile Thr Asn Lys Val Asn ser Val Ile Glu 25 30 Lys Met Asn Thr Gin Phe Glu Ala Val Gly Lys Leu Phe Xaa Asn Leu 40 45 Glu Lys Leu Glu Asn Leu Asn Lys Lys 50 55 <210> 252 <211> 26 <212> PRT <213> Influenza v rus <220 <221> MOD_RES <222> (20) <223> phe or ile <400> 252 His Ser Asn Asp Gin Gly Ser Gly Tyr Ala Ala Asp Lys Glu Ser Thr 1 5 10 15 Lys Ala Xaa Asp Gly lie Thr Asn Lys 25 <210> 253 - 115- 158109/1 <211> 21 <212> P T <213> Influenza virus <400> 253 His Asp Ser Asn val Arg Asn Leu tyr Asp Lys al Arg Met Gin Leu 1 5 10 15 Arg Asp Asn Ala Lys <210> 254 <211> 30 <212> PRT <213> Influenza virus <400> 254 His Lys cys Asp Asp Glu Cys Met Asn Ser val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Leu Asn Arg Asn Glu lie Lys Gly Val Lys 25 30 <210> 255 <211> 27 <212> PRT <213> Influenza virus <400> 255 His Lys Cys Asp Asp Glu cys Met Asn Ser val Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys Leu Asn Arg Asn Glu lie Lys 25 <210> 256 <211> 20 <212> PRT <213> Influenza v rus <400> 256 His Lys Cys Asp Asp Glu Cys Met Asn Ser al Lys Asn Gly Thr Tyr 1 5 10 15 Asp Tyr Pro Lys <210> 257 <211> 12 <212> PRT <213> Influenza v rus <400> 257 His Lys Cys Asp Asp Glu Cys Met Asn Ser val 1 5 10 <210> 258 <211> 27 <212> PRT <213> influenza <400> 258 Lys Gly. Ser Asn Tyr Pro Val Ala Lys Gly Ser Tyr Asn Asn Thr Asn -116- 158109/1 Gly Glu Gin lie Leu lie lie Trp Gly val His 25 <210> 259 <211> 43 <212> P T <213> influenza v rus <400> 259 ■ t ■ His ser Asn Asp Gin Gly Ser Gly Tyr Ala Ala Asp Lys Glu ser Thr 1 5 10 15 Gin Lys Ala al Asp Gly lie Thr Asn Lys Val Asn Ser Val lie Glu 25 30 Lys Met Asn Thr Gin Phe Glu Ala val Gly Lys 40 <210> 260 <211> 35 <212> PRT <213> influenza v rus <400> 260 Lys Arg Gly Ser Ser Gly lie Met Lys Thr Glu Gly Thr Leu Glu Asn 1 5 10 15 cys Glu Thr Lys Cys Gin Thr pro Leu Gly Ala lie Asn Thr Thr Leu 25 30 Pro Phe His <210> 261 <211> 16 <212> PRT <213> Influenza virus <400> 261 His Pro Leu Thr lie Gly Glu Cys Pro Lys Tyr val Lys Ser Glu Lys 1 5 10 15 <210 262 <211> 16 <212> PRT <213 Influenza virus <400> 262 His Ala Lys Asp lie Leu Glu Lys Thr His Asn Gly Lys Leu Cys Lys 1 5 10 15 <210> 263 <211> 25 <212> PRT <213> influenza virus <400> 263 His Asp Val Tyr Arg Asp Glu Ala Leu Asn Asn Arg Phe Gin lie Lys 1 5 10 15 Gly val Glu Leu Lys Ser Gly Tyr Lys - - 25 <210> 264 <211> 19 <212> PRT <213> influenza virus <400> 264 His Thr lie Asp Leu Thr Asp Ser Glu Met Asn Lys Leu Phe Glu Arg 1 5 10 15 Thr Arg Lys <210> 265 <211> 7 <212> PRT <213> influenza virus <400> 265 Lys Phe His Gin lie Glu Lys 1 5 <210> 266 <211> 11 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (8) <223> gly or gin <400> 266 Lys Thr Asn Glu Lys Phe His Xaa lie Glu 1 5 10 <210> 267 <211> 14 <212> PRT <213> influenza virus <220> <221> MOD^RES <222> (5) <223> val or leu <400> 267 Lys Leu Asn Arg Xaa lie Glu Lys Thr Asn Glu Lys Phe His 1 5 10 <210> 268 <211> 25 . <212> PRT <213> influenza virus <400> 268 His Gin He Glu Lys Glu Phe Ser Glu Val Glu Gly Arg lie Gin Asp 1 5 10 15 Leu Glu Lys Tyr Val Glu Asp Thr Lys 25 - 118- 158109/1 <210> 269 <211> 8 <212> PRT <213> influenza virus <400> 269 Lys lie cys Asn Asn Pro His Lys 1 5 <210> 270 <211> 14 <212> PRT <213> influenza virus <400> 270 Lys Leu Asn Arg val lie Lys Lys Thr Asn Glu Lys Phe His 1 5 10 <210> 271 <211> 24 <212> PRT <213> Influenza v rus <220> <221> MOD_RES <222> (3) <223> ile or val <220> <221> OD_RES <222> C17) <223> gly or gin <220> <221> MOD_RES <222> (20) <223> arg or lys <220> <221> MOD_RES <222> (22) <223> gin or gly <400> 271 His Asp Xaa Tyr Arg Asp Glu Ala Leu Asn Asn Arg Phe Gin lie Lys 1 5 10 15 Xaa Val Glu Xaa Ser Xaa Tyr Lys <210> 272 <211> 25 <212> PRT <213> Influenza v rus <400> 272 His Gin Ile Glu Lys Glu Phe Ser Glu Val Glu Gly Arg Ile Gin Asp 1 5 ' 10 15 Leu Glu Lys Tyr Val Glu Asp Thr Lys 25 <210> 273 <211> 25 - 119- 158109/1 <212> P T <213> influenza v rus <400> 273 Lys Tyr val Glu Asp Thr Lys lie Asp Leu Trp Ser Tyr Asn Ala Glu 1 5 10 15 Leu Leu Val Ala Leu Glu Asn Gin H s 25 <210> 274 <211> 49 <212> PRT <213> influenza virus <400> 274 Lys Tyr Val Lys Gin Asn Ser Leu Lys Leu Ala Thr Gly Met Arg Asn 1 5 10 15 Val Pro Glu Lys Gin Thr Arg Gly Leu Phe Gly Ala lie Ala Gly Phe 25 30 He Glu Asn Gly Trp Glu Gly Met lie Asp Gly Trp Tyr Gly Phe Arg 40 45 His <210> 275 <211 39 <212> PRT <213> Influenza virus <400> 275 Lys Glu Phe ser Glu Val Glu Gly Arg lie Gin Asp Leu Glu Lys Tyr 1 5 10 15 Val Glu Asp Thr Lys lie Asp Leu Trp Ser Tyr Asn Ala Glu Leu Leu 25 30 val Ala Leu Glu Asn Gin His <210> 276 <211> 33 <212> PRT <213> Influenza vi <220> <221> MOD_RES <222> (4) <223> ser or glu <220> <221> MOD_RES <222> (5) <223> glu or gin <220> <221> MOD_RES <222> (7) <223> thr or ser <220> <221> MOD_RES <222> (9) - 120- 158109/1 <223> gin or tyr <220> <221> MOD_RES <222> (13) <223> leu or gin <220> <221> OD_RES <222> (18) <223> ala or asn <220> <221> MOD_RES <222> (20) <223> ile or leu <220> <221> MOD_RES <222> (22) <223> gin or gly <220> <221> OD_RES <222> (24) <223> asn or thr <220> <221> OD_RES <222> (25) <223> gly or asn <220> <221> MOD_RES <222> (27) <223> leu or val <220> <221> MOD_RES <222> (29) <223> arg or ser <220> <221> OD_RES <222> (32) <223> glu or cys <400> 276 His Gin Asn Xaa Xaa Gly xaa Gly Xaa Ala Ala Asp xaa Lys Ser Thr 1 5 10 15 Gin xaa Ala xaa Asp Xaa lie xaa Xaa Lys xaa Asn xaa Val Ile Xaa 25 30 Lys <210> 277 <211> 18 <212> PRT <213> influenza <220> <221> OD_RES <222> (4) <223> gly or gin <220> <221> MOD_RES <222> C6) <223> gin or arg <220> <221> MOD_RES <222> (14) <223> val or ile <220> <221> MOD_RES <222> (17) <223> ser or thr <400> 277 ' , His cys Asp Xaa Phe Xaa Asn Glu Lys Trp Asp Leu Phe Xaa Glu Arg 1 5 10 15 Xaa Lys <210> 278 <211> 20 <212> PRT <213> Influenza v rus <400> 278 ' , His Thr Ile Asp Leu Thr Asp ser Glu Met Asn Lys Lys Leu Phe Glu 1 5 10 15 Arg Thr Arg Lys <210> 279 <211> 28 <212> PRT <213> influenza virus <400> 279 Lys Ser Gly Ser Thr Tyr Pro Leu Lys val Thr Met Pro Asn Asn 1 5 10 15 Asp Asn Phe Asp Lys Leu Tyr Trp Gly val His 25 <210> 280 <211> 34 <212> PRT <213> influenza virus <400> 280 Lys Leu Asn Trp Leu Thr Lys Ser Gly Asn Thr Tyr Pro val Leu Asn 1 5 10 15 val Thr Met Pro Asn Asn Asp Asn Phe Asp Lys Leu Val Ile Trp Gly 25 30 val H s <210> 281 <211> 19 <212> PRT <213> influenza virus <400> 281 - - H s Thr lie Asp Leu Thr Asp ser Glu Met Asn Lys Leu Phe Glu Lys 1 5 10 15 Thr Arg Lys <210> 282 <211> 18 <212> PRT <213> Influenza virus <400> 282 .

Lys Leu Asn Arg Leu lie Glu Lys Thr Asn Glu Lys Phe His Gin Thr 1 5 10 15 Glu Lys <210> 283 <211> 47 <212> PRT <213> influenza virus - <40d> 283 His Thr Gly Lys Ser ser Val Met Arg ser Asp Ala Pro lie Asp Phe 1 5 10 15 cys Asn ser Glu Cys lie Thr Pro Asn Gin ser lie Pro Asn Asp Lys 20 25 30 Pro Phe Gin Asn val Asn Lys lie Thr Tyr Gly Ala Cys Pro Lys 40 45 <210> 284 <211> 39 <212> PRT <213> Influenza virus <400> 284 His Thr Gly Lys Ser Ser Val Met Arg Ser Asp Ala Pro ie Asp Phe 1 5 10 15 Cys Asn Ser Glu Cys lie Thr Pro Asn Gin Ser lie Pro Asn Asp Lys 20 25 30 Pro Phe Gin Asn Val Asn Lys <210> 285 <211> 33 <212> PRT <213> influenza v rus <400> 285 His Pro Ser Thr Asp Ser Asp Gin Thr Ser Leu Tyr val Arg Ala Ser 1 5 10 15 Gly Arg val Thr Val Ser Thr Lys Arg Ser Gin Gin Thr Val lie Pro 20 25 30 Lys <210> 286 <211> 25 <212> PRT - 123- 158109/1 <213> Influenza virus <400> 286 Lys Tyr Val Glu Asp Thr Lys lie Asp Leu Trp Ser Tyr Asn Ala Glu 1 5 10 15 Leu Leu Val Ala Leu Glu Asn Gin His 25 <210> 287 <211> 26 <212> P T <213> Influenza virus <400> 287 -, -, ·, Lys Leu Phe Glu Arg Thr Arg Lys Gin Leu Arg Glu Asn Ala Glu Asp 1 5 10 15 Met Gly Asn Gly cys Phe Lys lie Tyr His 25 <210> 288 <211> 16 <212> PRT <213> influenza virus <400> 288 Lvs Arq Arq Ser lie Lys Ser Phe Phe Ser Arg Leu Asn Trp Leu His 1 5 10 15 <210> 289 <211> 16 <212> PRT <213> influenza virus <220> <221> MOD_RES <222> (12) <223> val or arg <400> 289 H s Pro val Thr lie Gly Glu Cys Pro Lys Tyr Xaa Lys Ser Thr Lys 1 5 10 15 <210> 290 <211> 30 <212> PRT <213> influenza virus <400> 290 Lys Gly Asn Ser Tyr Pro Lys Leu Ser Lys Leu ser Lys Ser Tyr lie 1 5 10 15 lie Asn Lys Lys Lys Glu Val Leu Val lie Trp Gly lie H s 25 30 <210> 291 <211> 24 <212> PRT <213> influenza v rus <220> <221> OD_RES - 124- 158109/1 <222> (9) <223> val or tyr <400> 291 Lys Leu Ser Lys Leu Ser Lys Ser Xaa lie lie Asn Lys Lys Lys Glu 1 5 10 15 al Leu val lie Trp Gly lie His <210> 292 <211> 21 <212> PRT <213> influenza v rus <220> <221> MOD_RES <222> (6) <223> val or tyr <400> 292 Lys Leu Ser Lys ser xaa lie lie Asn Lys Lys Lys Glu val Leu 1 5 10 15 lie Trp Gly lie His <210> 293 <211> 46 <212> PRT <213> Plasmodium falciparum <400> 293 Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Glu 1 5 10 15 Lys Glu Lys Glu Glu Lys Glu Lys Glu Glu Lys Glu Lys Glu Lys Glu 25 30 Glu Lys Glu Lys Glu Lys Glu Glu Lys Glu Glu Glu Lys Lys 40 45 <210> 294 <211> 48 <212> PRT <213> Plasmodium falciparum <400> 294 Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Glu 1 5 10 15 Lys Glu Lys Glu Glu Lys Glu Lys Glu Glu Lys Glu Lys Glu Lys Glu 25 30 Glu Lys Glu Lys Glu Lys Glu Glu Lys Glu Glu Glu Lys Lys Glu Lys 40 45 <210> 295 <211> 47 <212> PRT <213> Plasmodium falciparum <400> 295 Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys Glu Lys Glu Lys Glu Glu - - 1 5 10 15 Lys Glu Lys Glu Glu Lys Glu Lys Glu Lys Glu Glu Lys Glu Lys Glu 20 25 30 Glu Lys Glu Lys Glu Glu Lys Glu Glu Lys Glu Glu Glu Lys Lys 40 45 <210> 296 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 296 Lys Glu Glu Glu Glu Lys Glu Lys Glu Lys 1 5 10 <210> 297 <211> 19 <212> PRT <213> Plasmodium falc parum <400> 297 His Lys Lys Leu lie Lys Ala Leu Lys Lys Asn He Glu Ser lie Gin 1 5 10 15 Asn Lys Lys <210> 298 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 298 His Lys Lys Leu lie Lys Ala Leu Lys Lys Asn He Glu Ser lie Gin 1 5 10 15 Asn Lys Met <210> 299 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 299 His Lys Lys Leu lie Lys Ala Leu Lys Lys 1 5 10 <210> 300 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 300 His Lys Lys Leu lie Lys Ala Leu Lys 1 5 <210> 301 . <211> 23 <212> PRT <213> Plasmodium falc parum - 126- 158109/1 <400> 301 _ „ .

Lys Ala Thr Tyr ser Phe Val Asn Thr Lys Lys Lys lie lie Ser Leu 1 5 10 15 Lys Ser Gin Gly His Lys Lys <210> 302 <211> 22 <212> PRT <213> Plasmodium falciparum <400> 302 _ Lys Ala Thr Tyr ser Phe val Asn Thr Lys Lys Lys lie lie Ser Leu 1 5 10 15 Lys Ser Gin Gly His Lys <210> 303 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 303 Lys Ala Thr Tyr Ser Phe val Asn Thr Lys Lys Lys lie lie Ser Leu 1 5 10 15 Lys Ser Gin Gly Hi s <210> 304 <211> 29 <212> PRT <213> Plasmodium falciparum <400> 304 H s Thr Tyr Val Lys Gly Lys Lys Ala Pro ser Asp Pro Gin cys Ala 1 5 10 15 Asp lie Lys Glu Glu cys Lys Glu Leu Leu Lys Glu Lys 25 <210> 305 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 305 Lys lie lie Ser Leu Lys Ser Gin Gly His Lys 1 5 10 <210> 306 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 306 Lys Lys Lys Lys Phe Glu Pro Leu Lys Asn Gly Asn val Ser Glu Thr 1 5 10 15 lie Lys Leu lie His - - 158109/1 <210> 307 <211> 20 <212> P T <213> Plasmodium falciparum <400> 307 Lys Lys Lys Phe Glu Pro Leu Lys Asn Gly Asn Val Ser Glu Thr 1 5 10 . 15 Lys Leu lie His <210> 308 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 308 Lys Lys Phe Glu Pro Leu Lys Asn Gly Asn val ser Glu Thr lie Lys 1 5 10 15 Leu lie His <210> 309 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 309 Lys Asn Gly Asn Val Ser Glu Thr lie Lys Leu lie His 1 5 10 <210> 310 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 310 Lys Leu lie His Leu Gly Asn Lys Asp Lys Lys 1 5 10 <210> 311 <211> 36 <212> PRT <213> Plasmodium falciparum <400> 311 Lys Val Lys Lys lie Gly Val Thr Leu Lys Lys Phe Glu Pro Leu Lys 1 5 10 15 Asn Gly Asn Val -Ser Glu Thr lie Lys Leu lie His Leu Gly Asn Lys 25 30 Asp Lys Lys His <210> 312 <211> 59 <212> PRT <213> Plasmodium falciparum - 128 - 158109/1 <400> 312 H s Leu lie Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser Cys 1 5 10 15 val Lys Lys Met Asn Met Leu Lys Glu Asn Val Asp Tyr lie Gin Asn 25 30 Gin Asn Leu Phe Lys Glu Leu Met Asn Gin Lys Ala Thr Tyr Ser Phe 40 45 val Asn Thr Lys Lys Lys lie lie ser Leu Lys 50 , 55 <210> 313 <211> 52 <212> PRT <213> Plasmodium falciparum <400> 313 H s Leu lie Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser Cys 1 5 10 15 val Lys Lys Met Asn Met Leu Lys Glu Asn val Asp Tyr lie Gin Asn 25 30 Gin Asn Leu Phe Lys Glu Leu Met Asn Gin Lys Ala Thr Tyr Ser Phe 40 45 val Asn Thr Lys 50 <210> 314 <211> 43 <212> PRT <213> Plasmodium falciparum <400> 314 His Leu lie Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser cys 1 5 10 15 val Lys Lys Met Asn Met Leu Lys Glu Asn val Asp Tyr lie Gin Asn 25 30 Gin Asn Leu Phe Lys Glu Leu Met Asn Gin Lys 40 <210> 315 <211> 38 <212> PRT <213> Plasmodium falciparum <400> 315 His Leu lie Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser cys . 1 5 10 15 val Lys Lys Met Asn Met Leu Lys Glu Asn Val Asp Tyr H e Gin Lys 25 30 Asn Gin Asn Leu Phe Lys <210> 316 <211> 24 <212> PRT - 129- 158109/1 <213> Plasmodium falciparum <400> 316 His Leu lie Tyr Lys Asn Lys Ser Tyr Asn Pro Leu Leu Leu Ser Cys 1 . 5 10 15 Val Lys Lys Met Asn Met Leu Lys <210> 317 <211> 47 <212> P T <213> Plasmodium falciparum <400> 317 Lys Ser Ala Asn Asn Ser Ala Asn Asn Gly Lys Lys Asn Asn Ala Glu 1 5 10 15 Glu Met Lys Asn Leu val Asn Phe Leu Gin Ser His Lys Lys Leu lie 25 30 Lys Ala Leu Lys Lys Asn lie Glu ser lie Gin Asn Lys Lys His 40 45 <210> 318 <211> 37 <212> PRT <213> Plasmodium falciparum <400> 318 Lys Lys Asn Asn Ala Glu Glu Met Lys Asn Leu Val Asn Phe Leu Gin 1 5 10 15 Ser His Lys Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie 25 30 Gin Asn Lys Lys His <210> 319 <211> 29 <212> PRT <213> Plasmodium falciparum <400> 319 Lys Asn Leu Val Asn Phe Leu Gin Ser His Lys Lys Leu lie Lys Ala 1 5 10 15 Leu Lys Lys Asn lie Glu Ser lie Gin Asn Lys Lys His 25 <210> 320 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 320 Lys Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn 1 5 10 15 Lys Lys His <210> 321 - 130- 158109/1 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 321 Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn 1 5 10 15 Lys His <210> 322 <211> 12 <212> PRT <213> Plasmodium falciparum <400> 322 Lys Lys Asn lie Glu Ser lie Gin Asn Lys Lys His 1 5 10 <210> 323 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 323 Lys Asn lie Glu Ser lie Gin Asn Lys Lys His 1 5 10 <210> 324 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 324 Lys Asn Asn Ala Glu Glu Met Lys Asn Leu al Asn Phe Leu Gin ser 1 5 10 15 His <210> 325 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 325 Lys Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn 1 5 10 15 Lys Lys Gin Gly His Lys Lys <210> 326 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 326 Lys Lys Asn Asn Ala Glu Glu Met Lys Asn Leu val Asn Phe Leu Gin 1 5 10 15 ser His. Lys - 131 - 158109/1 <210> 327 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 327 Lys Asn Asn Ala Glu Glu Met Lys Asn Leu Val Asn Phe Leu Gin 1 5 10 15 His <210> 328 <211> 22 <212> PRT <213> Plasmodium falciparum <400> 328 Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn 1 5 10 15 Lys Gin Gly His Lys Lys <210> 329 <211> 28 <212> PRT <213> Plasmodium falciparum <400> 329 Lys Val Lys Lys lie Gly Val Thr Leu Lys Lys Phe Glu Pro Leu Lys 1 5 10 15 Asn Gly Asn- val Ser Glu Thr lie Lys Leu lie His 25 <210> 330 <211> 13 <212> PRT <213> Plasmodium falc parum <400> 330 Lys Asn Gly Asn val Ser Glu Thr lie Lys Leu lie His 1 5 10 <210> 331 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 31 Lys Leu lie His Leu Gly Asn Lys Asp Lys Lys 1 5 10 <210> 332 <211> 28 <212> PRT <213> Plasmodium falciparum <400> 332 Lys Ser Ala Asn Asn Ser Ala Asn Asn Gly Lys Lys Asn Asn Ala Glu 1 5 10 15 Glu Met Lys Asn Leu val Asn Phe Leu Gin Ser His - 132- 158109/1 25 <210> 333 <211> 18 <212> P T <213> Plasmodium falciparum <400> 333 Lys Lys Asn Asn Ala Glu Glu Met Lys Asn Leu Val Asn Phe Leu Gin 1 5 10 15 Ser His <210> 334 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 334 Lys Lys Leu lie Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn 1 5 10 15 Lys Lys His <210> 335 <211> 15 <212> PRT <213> Plasmodium falciparum <400> 335 Lys Ala Leu Lys Lys Asn lie Glu Ser lie Gin Asn Lys Lys His 1 5 10 15 <210> 336 <211> 12 <212> PRT <213> Plasmodium falciparum <400> 336 Lys Lys Asn lie Glu ser lie Gin Asn Lys Lys His 1 5 10 <210> 337 <211> 27 <212> PRT <213> Plasmodium falciparum <400> 337 Lys Glu Leu Met Asn Gin Lys Ala Thr Tyr Ser Phe Val Asn Thr Lys 1 5 10 15 Lys Lys lie lie Ser Leu Lys Ser Gin Gly His 25 <210> 338 <211> 7 <212> PRT <213> Plasmodium falciparum <400> 338 Lys Ser Gin Gly His Lys Lys 1 5 - 133- 158109/1 <210> 339 <211> 12 <212> PRT <213> Plasmodium falciparum <400> 339 Lys Lys Lys lie lie ser Leu Lys Ser Gin Gly His 1 5 10 <210> 340 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 340 Lys Lys lie lie Ser Leu Lys ser Gin Gly His 1 5 10 <210> 341 <211> 12 <212> PRT <213> Plasmodium falciparum <400 341 Lys Lys Asn lie Glu Ser He Gin Asn Lys Lys 1 5 10 <210 342 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 342 Lys Asn lie Glu Ser lie Gin Asn Lys Lys His 1 5 10 <210> 343 <211> 29 <212> PRT <213> Plasmodium falciparum <400> 343 His.Thr Tyr val Lys Gly Lys Lys Ala Pro ser Asp Pro Gin Cys Ala 1 5 10 15 Asp lie Lys Glu Glu cys Lys Glu Leu Leu Lys Glu Lys 25 <210> 344 <211> 27 « <212> PRT <213> Plasmodium falciparum <400> 344 His Thr Tyr val Lys Gly Lys Lys Ala Pro Ser Asp Pro Gin Cys Ala 1 5 10 15 Asp lie Lys Glu Glu Cys Lys Glu Leu Leu Lys 25 - 134- 158109/1 <210> 345 <211> 29 <212> PRT <213> Plasmodium falciparum <400> 345 His Glu Asn Val Leu ser Ala Ala Leu Glu Asn Thr Gin ser Glu Glu 1 5 10 15 Glu Lys Lys Glu Val lie Asp val lie Glu Glu Val Lys 25 <210> 346 <211> 48 <212> PRT <213> Plasmodium falciparum <400> 346 Lys Glu Asn Val Val Thr Thr lie Leu Glu Lys val Glu Glu Thr Thr 1 5 10 15 Ala Glu Ser Val Thr Thr Phe ser Asn lie Leu Glu Glu lie Gin Glu 25 30 Asn Thr lie Thr Asn Asp thr lie Glu Glu Lys Leu Glu Glu Leu His 40 45 <210> 347 <211> 14 <212> PRT <213> Plasmodium falciparum <400> 347 His Tyr Leu Gin Gin Met Lys Glu Lys Phe Ser Lys Glu Lys 1 5 10 <210> 348 <211> 42 <212> PRT <213> Plasmodium falciparum <400> 348 His Tyr Leu Gin Gin Met Lys Glu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn val lie Glu val Thr Asn Lys Ala Glu Lys Lys Gly Asn Val Gin 25 30 val Thr Asn Lys Thr Glu Lys Thr Thr Lys 40 <210> 349 <211> 46 <212> PRT <213> Plasmodium falciparum <400> 349 His Tyr Leu Gin Gin Met Lys Glu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn val lie Glu Val Thr Asn Lys Ala Glu Lys Lys Gly Asn val Gin 25 30 Val Thr Asn Lys Thr Glu Lys Thr Thr Lys Val Asp Lys Asn Asn Lys - 135 - 158109/1 40 45 <210> 350 <211> 57 <212> P T <213> Plasmodium falciparum <400> 350 His Tyr Leu Gin Gin Met Lys Glu Lys Phe ser Lys Glu Lys Asn Asn 1 5 10 15 Asn val lie Glu Val Thr Asn Lys Ala Glu Lys Lys Gly Asn Val Gin 25 30 Val Thr Asn Lys Thr Glu Lys Thr Thr Lys Val Asp Lys Asn Asn Lys 40 45 Val Pro Lys Lys Arg Arg Thr G n Lys 50 55 <210> 351 <211> 59 <212> PRT <213> Plasmodium falciparum <400> 351 His Tyr Leu Gin Gin Met Lys Glu Lys Phe Ser Lys Glu Lys Asn Asn 1 5 10 15 Asn Val lie Glu val Thr Asn Lys Ala Glu Lys Lys Gly Asn val Gin 25 30 Val Thr Asn Lys Thr Glu Lys Thr Thr Lys Val Asp Lys Asn Asn Lys 40 45 Val Pro Lys Lys Arg Arg Thr Gin Lys Ser Lys 50 55 <210> 352 <211> 52 <212> PRT <213> Plasmodium falciparum <400> 352 His val Asp Glu val Met Lys Tyr val Gin Lys lie Asp Lys Glu Val 1 5 10 15 Asp Lys Glu Val Ser Lys Ala Leu Glu Ser Lys Asn Asp Val Thr Asn 25 30 Val Leu Lys Gin Asn Gin Asp Phe Phe Ser Lys Val Lys Asn Phe val 40 45 Lys Lys Tyr Lys 50 <210> 35 <211> 50 <212> PRT <213> Plasmodium falciparum <400> 353 His Val Asp Glu val Met Lys Tyr Val Gin Lys lie Asp Lys Glu Val 1 5 10 15 - 136- 158109/1 Asp Lys Glu Val Ser Lys Ala Leu Glu ser Lys Asn Asp Val Thr Asn 25 30 val Leu Lys Gin Asn Gin Asp Phe Phe ser Lys val Lys Asn Phe val 40 45 Lys Lys 50 <210> 354 <211> 43 <212> PRT <213> Plasmodium falciparum <400> 354 His val Asp Glu Val Met Lys Tyr Val Gin Lys lie Asp Lys Glu Val 1 5 10 15 Asp Lys Glu Val Ser Lys Ala Leu Glu ser Lys Asn Asp val Thr Asn 25 30 Val Leu Lys Gin Asn Gin Asp Phe Phe Ser Lys 40 <210> 355 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 355 His Val Asp Glu Val Met Lys Tyr Val Gin Lys lie Asp Lys Glu Val 1 5 10 15 Asp Lys Glu Val Ser Lys Ala Leu Glu Ser Lys Asn Asp val Thr Asn 25 30 val Leu Lys <210> 356 <211> 27 <212> PRT <213> Plasmodium falciparum <400> 356 His Val Asp Glu val Met Lys Tyr al Gin Lys lie Asp Lys Glu 1 5 10 15 Asp Lys Glu Val Ser Lys Ala Leu Glu Ser Lys 25 <210> 357 <211> 22 <212> PRT <213> Plasmodium falciparum <400> 357 His Val Asp Glu Val Met Lys Tyr Val Gin Lys lie Asp Lys Glu 1 5 10 15 Asp Lys Glu val Ser Lys - 137- 158109/1 <210> 358 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 358 His Val Asp Glu val Met Lys Tyr val Gin Lys lie Asp Lys Glu 1 5 10 15 Asp Lys <210> 359 <211> 14 <212> P T <213> Plasmodium falciparum <400> 359 H s Val Asp Glu Val Met Lys Tyr Val Gin Lys lie Asp Lys 1 5 10 <210> 360 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 360 Lys Asp Glu Val lie Asp Leu lie val Gin Lys Glu Lys Arg lie Glu 1 5 10 15 Lys Val Lys Ala Lys Lys Lys Lys Leu Glu Lys Lys Val Glu Glu Gly 25 30 Val Ser Gly Leu Lys Lys His <210> 361 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 361 Lys val Lys Ala Lys Lys Lys Lys Leu Glu Lys Lys Val Glu Glu 1 5 10 15 val ser Gly Leu Lys Lys His <210> 362 <211> 21 <212> PRT <213> Plasmodium falc parum <400> 362 Lys Ala Lys Lys Lys Lys Leu Glu Lys Lys val Glu Glu Gly val Ser 1 5 10 15 Gly Leu Lys Lys His <210> 363 <211> 19 <212> PRT - - 158109/1 <213> Plasmodium falciparum <400> 363 Lys Lys Lys Lys Leu Glu Lys Lys val Glu Glu Gly val ser Gly Leu 1 5 10 15 Lys Lys His <210> 364 <211> 18 <212> P T <213> Plasmodium falciparum <400> 364 Lys Lys Lys Leu Glu Lys Lys val Glu Glu Gly val ser Gly Leu Lys 1 5 10 15 Lys His <210> 365 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 365 Lys Lys Leu Glu Lys Lys val Glu Glu Gly Val Ser Gly Leu Lys 1 5 10 15 His <210> 366 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 366 Lys Leu Glu Lys Lys val Glu Glu Gly val Ser Gly Leu Lys Lys His 1 5 10 15 <210> 367 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 367 Lys Lys Val Glu Glu Gly Val Ser Gly Leu Lys Lys His 1 5 10 <210> 368 <211> 12 <212> PRT <213> Plasmodium falciparum <400> 368 Lys val Glu Glu Gly val Ser Gly Leu Lys Lys His 1 5 10 <210> 369 <211> 59 <212> PRT <213> Plasmodium falciparum <400> 369 His al Glu Gin Asn val Tyr Val Asp val Asp Val Pro Ala Met Lys 1 5 10 15 Asp Gin Phe Leu Gly lie Leu Asn Glu Ala Gly Gly Leu Lys Glu Met 25 30 Phe Phe Asn Leu Glu Asp Val Phe Lys Ser Glu Ser Asp val lie Thr 35 40 45 val Glu Glu lie Lys Asp Glu Pro val Gin Lys 50 55 <210> 370 <211> 53 <212> PRT <213> Plasmodium falciparum <400> 370 His lie Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu Val Asp Asp Leu 1 5 10 15 Lys Gly ser lie Leu Asp Met Leu Lys Gly Asp Met Glu Leu Gly Asp 25 30 Met Asp Lys Glu Ser Leu Glu Asp Val Thr Thr Lys Leu Gly Glu Arg 35 40 45 Val Glu Ser Leu Lys 50 <210> 371 <211> 44 <212> PRT <213> Plasmodium falciparum <400> 371 H s lie Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu val Asp Asp Leu 1 5 10 15 Lys Gly Ser lie Leu Asp Met Leu Lys Gly Asp Met Glu Leu Gly Asp 25 30 Met Asp Lys Glu ser Leu Glu Asp Val Thr Thr Lys 40 <210> 372 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 372 His lie Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu val Asp Asp Leu 1 , 5 10 15 Lys Gly Ser lie Leu Asp Met Leu Lys Gly Asp Met Glu Leu Gly Asp 25 30 Met Asp Lys <210> 373 <211> 25 <212> PRT - 140- 158109/1 <213> Plasmodium falciparum <400> 373 His lie Lys Gly Leu Glu Glu Asp Asp Leu Glu Glu Val Asp Asp Leu 1 - 5 10 15 Lys Gly Ser lie Leu Asp Met Leu Lys 25 <210> 374 <211> 31 <212> PRT <213> Plasmodium falciparum <400> 374 His lie lie Ser Gly Asp Ala Asp al Leu ser ser Ala Leu Gly Met 1 5 10 15 Asp Glu Glu Gin Met Lys Thr Arg Lys Lys Ala Gin Arg Pro Lys 25 30 <210> 375 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 375 His Asp lie Thr Thr Thr Leu Asp Glu Val val Glu Leu Lys Asp Val 1 5 10 15 Glu Glu Asp Lys lie Glu Lys <210> 376 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 376 Lys Lys Leu Glu Glu Val His Glu Leu Lys 1 5 10 <210 377 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 377 Lys Leu Glu Glu val His Glu Leu Lys 1 5 <210> 378 , <211> 19 <212> PRT <213> Plasmodium falciparum <400> 378 Lys Thr lie Glu Thr Asp lie Leu Glu Glu Lys Lys Lys Glu lie Glu 1 5 10 15 Lys Asp Hi s <210> 379 <211> 11 <212> P T <213> Plasmodium falciparum <400> 379 Lys Lys Glu lie Glu Lys Asp His Phe Glu Lys 1 5 10 <210> 380 <211> 6 <212> PRT <213> Plasmodium falciparum <400> 380 Lys Asp H s Phe Glu Lys 1 5 <210> 381 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 381 Lys Phe Glu Glu Glu Ala Glu Glu lie Lys His 1 5 10 <210> 382 <211> 47 <212> PRT <213> Plasmodium falciparum <400> 382 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 Cys lie Lys His Lys Ser Asp His Asn His Lys ser Asp His Asn His 25 30 Lys Ser Asp Pro Asn His Lys Lys Lys Asn Asn Asn Asn Asn Lys 40 45 <210> 383 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 383 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 cys lie Lys His Lys Ser Asp His Asn His Lys ser Asp His Asn His 25 30 Lys Ser Asp Pro Asn His Lys Lys 40 <210> 384 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 384 - 142 - 158109/1 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu'cys Ala Gin" Gly Lys Lys 1 5 10 15 cys lie Lys His Lys Ser Asp His Asn His Lys Ser Asp His Asn His 25 30 Lys Ser Asp pro Asn His Lys <210> 385 <211> 33 <212> PRT <213> Plasmodium falciparum <400> 385 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 Cys lie Lys His Lys ser Asp His Asn His Lys Ser Asp His Asn His 25 30 Lys <210> 386 <211> 27 <212> PRT <213> Plasmodium falciparum <400> 386 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 Cys lie Lys His Lys Ser Asp His Asn His Lys 25 <210> 387 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 387 Lys Asp Gly Asp Thr Lys cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 Cys lie Lys His Lys <210> 388 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 388 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys Lys 1 5 10 15 <210> 389 <211> 15 <212> PRT <213> Plasmodium falciparum <400> 389 Lys Asp Gly Asp Thr Lys Cys Thr Leu Glu Cys Ala Gin Gly Lys - 143 - 158109/1 1 5 10' " 15 <210> 390 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 390 Lys Cys lie Gin Ala Glu cys Asn Tyr Lys Glu Cys Gly Glu Gin 1 5 10 15 Cys Val Trp Asp Gly lie His <210> 391 <211> 14 <212> PRT <213> Plasmodium falciparum <400> 391 Lys Glu Cys Gly Glu Gin Lys cys val Trp Asp Gly lie His 1 5 10 <210> 392 <211> 32 <212> PRT <213> Plasmodium falciparum <400> 392 His lie Glu Cys Lys Cys Asn Asn Asp Tyr al Leu Thr Asn Arg Tyr 1 5 10 15 Glu Cys Glu Pro Lys Asn Lys Cys Thr Ser Leu Glu Asp Thr Asn Lys 25 30 <210> 393 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 393 Lys ser Asp His Asn His Lys Ser Asp His Asn His Lys ser Asp His 1 5 10 15 Asn His Lys Ser Asp His Asn His Lys Ser Asp Pro Asn His Lys Lys 25 30 Lys Asn Asn Asn Asn Asn Lys <210> 394 <211> 33 <212> PRT <213> Plasmodium falciparum <400 394 Lys Ser Asp H s Asn His Lys Ser Asp His Asn His Lys Ser Asp His 1. 5 10 15 Asn His Lys Ser Asp Pro Asn His Lys Lys Lys Asn Asn Asn Asn Asn 25 30 Lys <210> 395 <211> 27 <212> PRT <213> Plasmodium falciparum <400> 395 Lys Ser Asp His Asn His Lys Ser Asp His Asn His Lys Ser Asp Pro 1 5 10 15 Asn His Lys Lys Lys Asn Asn Asn Asn Asn Lys 25 <210> 396 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 396 Lys Ser Asp His Asn His Lys Ser Asp Pro Asn His Lys Lys Lys Asn 1 5 10 15 Asn Asn Asn Asn Lys <210> 397 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 397 Lys Lys Lys Asn Asn Asn Asn Asn Lys Asp Asn Lys Ser Asp Pro Asn 1 5 10 15 His Lys <210> 398 <213> 17 <212> PRT <213> Plasmodium falciparum <400> 398 . Lys Lys Asn Asn Asn Asn Asn Lys Asp Asn Lys Ser Asp Pro Asn His 1 5 10 15 Lys <210> 399 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 399 Lys Asn Asn Asn Asn Asn Lys Asp Asn Lys Ser Asp Pro Asn His Lys 1 5 10 15 <210> 400 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 400 - - Lys Asp Asn Lys Ser Asp Pro Asn His Lys 1 5 10 <210> 401 <211> 7 <212> PRT <213> Plasmodium falciparum <400> 401 Lys Ser Asp Pro Asn His Lys 1 5 <210> 402 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 402 His ser Leu Tyr Ala Leu Gin Gin Asn Glu Glu Tyr Gin Lys Val Lys 1 5 10 15 Asn Glu Lys Asp Gin Asn Glu lie Lys Lys. lie Lys Gin Leu lie Glu 25 30 Lys Asn Lys <210> 403 <211> 28 <212> PRT <213> Plasmodium falciparum <400> 403 His Ser Leu Tyr Ala Leu Gin Gin Asn Glu Glu Tyr Gin Lys Val Lys 1 5 10 15 Asn Glu Lys Asp Gin Asn Glu lie Lys Lys lie Lys 25 <210> 404 <211> 26 <212> PRT <213> Plasmodium falciparum <400> 404 His Ser Leu Tyr Ala Leu Gin Gin Asn Glu Glu Tyr Gin Lys Val Lys 1 5 10 15 Asn Glu Lys Asp Gin Asn Glu lie Lys Lys 25 <210> 405 <211> 25 <212> PRT <213> Plasmodium falciparum <400> 405 His Ser Leu Tyr Ala Leu Gin Gin Asn Glu Glu Tyr Gin Lys Val 1 5 10 15 Asn Glu Lys Asp Gin Asn Glu lie Lys 25 - 146- 158109/1 <210> 406 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 406 His Lys Leu Glu Asn Leu Glu Glu Met Asp Lys 1 5 10 <210> 407 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 407 Lys H s Phe Asp Asp Asn Thr Asn Glu Gin Lys 1 5 10 <210> 408 <211> 8 <212> PRT <213> Plasmodium falciparum <400> 408 Lys Lys Glu Asp Asp Glu Lys His 1 5 <210> 409 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 409 Lys Glu Glu Asn Asn Lys Lys Glu Asp Asp Glu Lys His 1 5 10 <210> 410 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 410 Lys Thr Ser Ser Gly lie Leu Asn Lys Glu Glu Asn Asn Lys Lys Glu 1 5 10 15 Asp Asp Glu Lys His <210> 411 <211> 7 <212> PRT <213> Plasmodium falciparum <400> 411 Lys Asn lie His lie Lys Lys 1 5 <210> 412 <211>.13 <212> PRT <213> Plasmodium f al ci parum - 147- 158109/1 <400> 412 His lie Lys Lys Lys Glu Gly lie Asp lie Gly Tyr Lys 1 5 10 <210> 413 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 413 ■ Lys Lys Met Trp Thr Cys Lys Leu Trp Asp Asn Lys Gly Asn Glu lie 1 5 10 15 Thr Lys Asn lie His <210> 414 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 414 Lys Lys Gly lie Gin Trp Asn Leu Leu Lys Lys Met Trp Thr Cys 1 5 10 15 Leu Trp Asp Asn Lys Gly Asn Glu lie Thr Lys Asn lie His 25 30 <210> 415 <211> 50 <212> PRT <213> Plasmodium falciparum <400> 415 Lys Glu Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu 1 5 10 15 Asp Lys Lys Asn Pro Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys 25 30 lie Thr His Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn Asn Val 40 45 Thr His 50 <210> 416 <211> 48 <212> PRT <213> Plasmodium falciparum <400> 416 ' ' ■ Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu Asp Lys 1 5 10 15 Lys Asn Pro Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys lie Thr 25 30 His Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn Asn Val Thr His . 40 45 <210> 417 - 148 - 158109/1 <211> 47 <212> P T <213> Plasmodium falciparum <400> 417 Lys As Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu Asp Lys Lys 1 5 10 15 Asn Pro Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys lie Thr His 25 30 Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn Asn Val Thr H s 40 45 , . <210> 418 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 418- Lys Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Lys Leu Lys Lys lie 1 5 10 15 Glu Tyr Thr Asn Lys lie Thr His Phe Phe Lys Ala Lys Asn Asn Lys 25 30 Gin Gin Asn Asn Val Thr His <210> 419 <211> 38 <212> PRT <213> Plasmodium falciparum <400> 419 Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Lys Leu Lys Lys lie Glu 1 5 10 15 Tyr Thr Asn Lys lie Thr H s Phe Phe Lys Ala Lys Asn Asn Lys Gin 25 30 Gin Asn Asn Val Thr His <210> 420 <211> 36 <212> PRT <213> Plasmodium falciparum <400> 420 Lys Glu Asp Lys Lys Asn Pro Asn Lys Leu Lys Lys lie Glu Tyr Thr 1 5 10 15 Asn Lys lie Thr His Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn 25 30 Asn Val Thr His <210> 421 <211> 32 <212> PRT <213> Plasmodium falciparum - 149 - 158109/1 <400> 421 Lys Asn Pro Asn Lys Leu Lys Lys lie. Glu Tyr Thr Asn Lys lie Thr 1 5 10 15 His Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn Asn val Thr His 25 30 <210> 422 <211> 26 <212> PRT <213> Plasmodium falciparum <400> 422 Lys Lys lie Glu Tyr Thr Asn Lys lie Thr His Phe Phe Lys Ala Lys 1 5 10 15 Asn Asn Lys Gin Gin Asn Asn Val Thr His 25 <210> 423 <211> 25 <212> PRT <213> Plasmodium falciparum <400> 423 Lys lie Glu Tyr Thr Asn Lys lie Thr His Phe Phe Lys Ala Lys Asn 1 5 10 15 Asn Lys Gin Gin Asn Asn Val Thr His 25 <210> 424 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 424 Lys lie Thr His Phe Phe Lys Ala Lys Asn Asn Lys Gin Gin Asn Asn 1 5 10 15 Val Thr His <210> 425 <211> 48 <212> PRT <213> Plasmodium falciparum <400> 425 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 25 30 Asn Asp Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 40 45 <210> 426 <211> 45 <212> PRT <213> Plasmodium falciparum <400> 426 - 150- 158109/1 His Lys Asn Asn Glu Asp lie Lys Asn Asp 'Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 25 30 Asn Asp Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys 40 45 <210> 427 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 427 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn ser Lys Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 25 30 Asn Asp Asn Asn Glu Asp lie Lys 40 <210> 428 <211> 32 <212> PRT <213> Plasmodium falciparum <400> 428 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 25 30 <210> 429 <211> 29 <212> PRT <213> Plasmodium falciparum <400> 429 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie 1 5 10 15 Asn Asp Asn Ser Lys Asp lie Lys Asn Asp Asn Ser Lys 25 <210> 430 <211> 24 <212> PRT <213> Plasmodium falciparum <400> 430 ' His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn Ser Lys Asp lie Lys <210> 431 <211> 21 <212> PRT - 151 - 158109/1 <213> Plasmod um falciparum <400> 431 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 Asn Asp Asn Ser Lys <210> 432 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 432 His Lys Asn Asn Glu Asp lie Lys Asn Asp Asn Ser Lys Asp lie Lys 1 5 10 15 <210> 433 <211> 8 <212> PRT <213> Plasmodium falciparum <400> 433 His Lys Asn Asn Glu Asp lie 1 5 <210> 434 <211> 31 <212> PRT <213> Plasmodium falciparum <400> 434 Lys Lys Tyr Asp Asp Leu Gin Asn Lys Tyr Asn lie Leu Asn Lys Leu 1 5 10 15 Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 25 30 <210> 435 <211 30 <212> PRT <213 Plasmodium falciparum <400> 435 Lys Tyr Asp Asp Leu Gin Asn Lys Tyr Asn lie Leu Asn Lys Leu 1 5 10 15 Asn ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys. Tyr His 25 30 <210> 436 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 436 Lys Tyr Asn lie Leu Asn Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn 1 5 10 15 Glu Glu Leu Lys Lys Tyr His - 152 - 158109/1 <210> 437 <211> 17 <212> PRT <213> Plasmodium fal ciparum <400> 437 Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr 1 5 10 15 His <210> 438 <211> 15 <212> PRT <213> Plasmodium falc parum <400> 438 Lys Asn ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 1 5 10 15 <210> 439 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 439 Lys Asn Glu Glu Leu Lys Lys Tyr His 1 5 <210> 440 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 440 His Met Gly Asn Asn Gin Asp lie Asn Glu Asn Val Tyr Asn He Lys 1 5 10 15 pro Gin Glu Phe Lys Glu Glu Glu Glu Glu Asp lie Ser Met Val Asn 25 30 Thr Lys Lys <210> 441 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 441 Lys Asn Ser Asn Glu Leu Lys Arg lie Asn Asp Asn Phe Phe Lys Leu 1 5 10 15 His <210> 442 <211> 55 <212> PRT <213> Plasmodium falciparum <400> 442 Lys Pro Cys Leu Tyr Lys Lys Cys Lys lie Ser Gin Cys Leu Tyr Lys - 153 - 158109/1 1 5 10 15 Lys cys Lys lie Ser Gin Val Trp Trp Cys Met Pro Val Lys Asp Thr 25 30 Phe Asn Thr Tyr Glu Arg Asn Asn Val Leu Asn Ser Lys lie Glu Asn 40 45 Asn lie Glu Lys lie Pro H s 50 55 <210> 443 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 443 His lie Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 10 15 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn lie Lys Asp Tyr 25 30 lie Asn Ser Met Asn Phe Lys Lys 40 <210> 444 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 444 His lie Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 10 15 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn lie Lys Asp Tyr 25 30 lie Asn Ser Met Asn Phe Lys <210> 445 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 445 His lie Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 5 10 15 Tyr Lys <210> 446 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 446 Lys Asn Lys Thr Asn Gin Ser Lys Gly val Lys Gly Glu Tyr Glu 1 5 . 10 15 Lys Lys Glu Thr Asn Gly His - 154- 158109/1 <210> 447 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 447 Lys Thr Asn Gin Ser Lys Gly val Lys Gly Glu Tyr Glu Lys Lys Lys 1 5 10 15 Glu Thr Asn Gly His <210> 448 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 448 Lys Gly val Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 15 <210> 449 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 449 Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 <210> 450 <211> 28 <212> PRT <213> Plasmod um falciparum <400> 450 Lys Ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser Cys Glu cys Ser. 1 5 10 15 Tyr Lys Lys Lys Ser Ser Ser ser Asn Lys val His 25 <210> 451 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 451 Lys Ser Cys Glu Cys Ser Tyr Lys Lys Lys Ser ser Ser Ser Asn Lys 1 5 10 15 Val His <210> 452 <211> 11 <212> PRT. <213> Plasmodium falciparum <400> 452 Lys Lys Lys Ser Ser Ser ser Asn Lys val His 1 5 10 <210 453 <211> 10 <212> P T <213> Plasmodium falciparum <400> 453 Lys Lys Ser Ser Ser Ser Asn Lys val 1 5 <210> 454 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 454 Lys Ser Ser Ser Ser Asn Lys Val 1 5 <210> 455 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 455 His lie Met Leu Lys Ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 cys Glu Cys ser Tyr Lys Lys Lys Ser ser Ser Ser Asn Lys 25 30 <210> 456 <211> 24 <212> PRT <213> Plasmodium falciparum <400> 456 His lie Met Leu Lys Ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys <210> 457 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 457 His lie Met Leu Lys Ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu cys Ser Tyr Lys Lys <210> 458 <211> 22 <212> PRT <213> Plasmodium falciparum <400> 458 His lie Met Leu Lys ser Gly Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 - 156 - 158109/1 Cys Glu Cys Ser Tyr Lys <210> 459 <211> 50 <212> P T <213> Plasmodium falciparum <400> 459 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp Val He lie Asp Asn Thr Glu lie Gin 25 30 Lys lie lie lie Arg Asp Tyr His Glu Thr Leu Asn Val His Lys Leu 40 45 Asp His 50 <210> 460 <211> 43 <212> PRT <213> Plasmodium falciparum <400> 460 Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 Val lie He Asp Asn Thr Glu lie Gin Lys lie lie lie Arg Asp Tyr 25 30 His Glu Thr Leu Asn val His Lys Leu Asp His 40 <210> 461 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 461 Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp val lie lie 1 5 10 15 Asp Asn Thr Glu He Gin Lys lie He lie Arg Asp Tyr His Glu Thr 25 30 Leu Asn Val His Lys Leu Asp His 40 <210> 462 <211> 46 <212> PRT <213> Pi asmodi urn f al ci parum <400> 462 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu. Arg Gly Asp Val lie lie Asp Asn Thr Glu l e Gin 25 30 - 157- 158109/1 Lys lie lie lie Arg Asp Tyr His Glu Thr Leu Asn Val His 40 45 <210> 463 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 463 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp val lie lie Asp Asn Thr Glu lie Gin 25 30 Lys lie He lie Arg Asp Tyr His 40 <210> 464 <211> 36 <212> PRT <213> Plasmodium falciparum <400> 464 Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu 1 5 10 15.

Arg Gly Asp val lie lie Asp Asn Thr Glu lie Gin Lys lie lie lie 25 30 Arg Asp Tyr His <210> 465 <211> 33 <212> PRT <213> Plasmodium falciparum <400> 465 Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 Val lie lie Asp Asn Thr Glu lie Gin Lys lie lie lie Arg Asp Tyr 25 30 His <210> 466 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 466 Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp Val lie 1 5 10 15 Asp Asn Thr Glu He Gin Lys lie lie lie Arg Asp Tyr His 25 30 <210> 467 <211> 41 <212> PRT <213> Plasmodium falciparum <400> 467 Lys Lys Asp Lys Glu Lys Lys Lys Asp ser Asn Glu Asn Arg Lys Lys 1 5 10 15 Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys 25 30 He Glu Tyr Thr Asn Lys lie Thr H s 40 <210> 468 <211> 40 <212> P T <213> Plasmodium falciparum <400> 468 Lys Asp Lys Glu Lys Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys 1 5 10 15 Gin Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie 25 30 Glu Tyr Thr Asn Lys lie Thr His 40 <210> 469 <211> 38 <212> PRT <213> Plasmodium falciparum <400> 469 Lys Glu Lys Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys • 1 5 10 15 Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr 25 30 Thr Asn Lys lie Thr His <210> 470 <211> 36 <212> PRT <213> Plasmodium falciparum <400> 470 Lys Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu Asp 1 5 10 15 Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn 25 30 Lys lie Thr His ' <210> 471 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 471 Lys Lys Asp Ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu Asp Lys 1 5 10 15 - 159 - 158109/1 Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys 25 30 lie Thr H s <210> 472 <211> 34 _<212> P T <213> Plasmodium falciparum <400> 472 Lys Asp ser Asn Glu Asn Arg Lys Lys Lys Gin Lys Glu Asp Lys Lys 1 5 10 15 Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys lie 25 30 Thr His <210> 473 <211> 27 <212> PRT <213> Plasmodium falciparum <400> 473 Lys Lys Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu 1 5 10 15 Lys Lys lie Glu Tyr Thr Asn Lys lie Thr His 25 <210> 474 <211> 26 <212> PRT <213> Pi asmod urn f al ci parum <400> 474 Lys Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys 1 5 10 15 Lys lie Glu Tyr Thr Asn Lys lie Thr His 25 <210> 475 <211> 25 <212> PRT <213> Plasmodium falciparum <400> 475 Lys Gin Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys 1 5 , 10 15 lie Glu Tyr Thr Asn Lys lie Thr His 25 <210> 476 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 476 - 160- 158109/1 Lys Glu Asp Lys Lys Asn Pro Asn Asp Asn' Lys Leu Lys" Lys lie 1 5 10 15 Tyr Thr Asn Lys lie Thr His <210> 477 <211> 20 <212> PRT <213> Plasmod um falciparum <400> 477 Lys Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn 1 5 10 15 Lys lie Thr His <210> 478 <211> 19 <212> PRT <213> Plasmodium falciparum <400> 478 Lys Asn Pro Asn Asp Asn Lys Leu Lys Lys lie Glu Tyr Thr Asn 1 5 10 15 lie Thr His <210> 479 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 479 Lys Leu Lys Lys lie Glu Tyr Thr Asn Lys lie Thr His 1 5 10 <210> 480 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 480 Lys Lys lie Glu Tyr Thr Asn Lys lie Thr His 1 5 10 <210> 481 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 481 Lys lie Glu Tyr Thr Asn Lys lie Thr His 1 5 10 <210> 482 <211> 44 <212> PRT <213> Plasmodium falc parum <400> 482 -161- 158109/1 His Gly Gin lie Lys lie Glu Asp val Asn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gin Met Lys Asn Lys Tyr Asn Asp Glu Glu Lys Met Asp lie ser 25 30 Lys Ser Lys Ser Leu Lys ser Asp Phe Leu Glu Lys 40 <210> 483 <211> 38 <212> PRT <213> Plasmod um falciparum <400> 483 His Gly Gin lie Lys lie Glu Asp val Asn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gin Met Lys Asn Lys Tyr Asn Asp Glu Glu Lys Met Asp lie Ser 25 30 Lys Ser Lys Ser Leu Lys <210> 484 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 484 His Gly Gin lie Lys lie Glu Asp Val Asn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gin Met Lys Asn Lys Tyr Asn Asp Glu Glu Lys Met Asp lie Ser 25 30 Lys ser Lys <210> 485 <211> 33 <212> PRT <213> Plasmodium falciparum <400> 485 His Gly Gin lie Lys lie Glu Asp Val Asn Asn Glu Asn Phe Asn Asn 1 5 10 15 Glu Gin Met Lys Asn Lys Tyr Asn Asp Glu Glu Lys Met Asp lie Ser 25 30 Lys <210> 486 <211> 31 <212> PRT <213> Plasmodium falciparum <400> 486 Lys Lys Tyr Asp Asp Leu Gin Asn Lys Tyr Asn lie Leu Asn Lys. Leu 1 5 10 15 Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr H s 25 30 - 162- 158109/1 <210> 487 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 487 Lys Tyr Asp Asp Leu Gin Asn Lys Tyr Asn lie Leu Asn Lys Leu Lys 1 5 10 15 Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 25 30 <210> 488 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 488 Lys Tyr Asn lie Leu Asn Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn 1 5 10 15 Glu Glu Leu Lys Lys Tyr His <210> 489 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 489 Lys Leu Lys Asn Ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr 1 5 10 15 His <210> 490 <211> 15 <212> PRT <213> Plasmodium falciparum <400> 490 Lys Asn ser Leu Glu Glu Lys Asn Glu Glu Leu Lys Lys Tyr His 1 5 10 15 <210> 491 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 491 Lys Asn Glu Glu Leu Lys Lys Tyr 1 5 <210> 492 <211> 44 <212> PRT ■ . <213> Plasmodium falciparum <400> 492 His Met Gly Asn Asn Gin Asp lie Asn Glu Asn val Tyr Asn lie Lys 1 5 10 15 - 163- 158109/1 Pro Gin Glu Phe Lys Glu Glu Glu Glu Glu Asp lie ser Met val Asn 25 30 Thr Lys Lys cys Asp Asp lie Gin Glu Asn lie Lys 40 <210> 493 <211> 50 <212> PRT <213> Plasmodium falciparum <400> 493 Lys Thr Asn Leu Tyr Asn lie Tyr Asn Asn Lys Asn Asp Asp Lys Asp 1 5 10 15 Asn lie Leu Asp Asn Glu Asn Arg Glu Gly Leu Tyr Leu Cys Asp Val 25 30 Met Lys Asn Ser Asn Glu Leu Lys Arg lie Asn Asp Asn Phe Phe Lys 40 45 Leu His 50 <210> 494 <211 17 <212> PRT <213> Plasmodium falciparum <400> 494 Lys Asn ser Asn Glu Leu Lys Arg lie Asn Asp Asn Phe Phe Lys Leu 1 5 10 15 His <210> 495 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 495 Lys Arg lie Asn Asp Asn Phe Phe Lys Leu His 1 5 10 <210> 496 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 496 His lie Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn Cys Leu Leu 1 - 5 . 10 15 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn lie Lys Asp Tyr 25 30 lie Asn Ser Met Asn Phe Lys Lys 40 <210> 497 <211> 39 <212> PRT - - <213> Plasmodium falciparum <400> 497 His l e Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn cys Leu Leu 1 5 10 15 Tyr Lys Asn Glu Glu Arg Asn Tyr Asn Asp Asn Asn lie Lys Asp Tyr 25 30 lie Asn Ser Met Asn Phe Lys <210> 498 <211> 18 <212> PRT <213> Plasmodium falciparum <400> 498 His lie Asn Asn Glu Tyr Thr Asn Lys Asn Pro Lys Asn cys Leu Leu 1 5 10 15 Tyr Lys <210> 499 <211> 45 <212> PRT <213> Plasmodium falciparum <400> 499 Lys Pro Cys Leu Tyr Lys Lys Cys Lys lie Ser Gin val Trp Trp Cys 1 5 10 15 Met Pro Val Lys Asp Thr Phe Asn Thr Tyr Glu Arg Asn Asn Val Leu 25 30 Asn Ser Lys lie Glu Asn Asn lie Glu Lys lie Pro His 40 45 <210> 500 <211> 39 <212> PRT <213> Plasmodium falciparum <400> 500 Lys Cys Lys lie Ser Gin Val Trp Trp Cys Met Pro val Lys Asp Thr 1 5 10 15 Phe Asn Thr Tyr Glu Arg Asn Asn Val Leu Asn ser Lys He Glu Asn 25 30 Asn lie Glu Lys lie Pro His <210> 501 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 501 Lys lie Glu Asn Asn lie Glu Lys lie Pro 1 5 10 <210> 502 -165- 158109/1 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 502 Lys Asn Lys Thr Asn Gly Ser Lys Gly val Lys Gly Glu Tyr Glu 1 5 10 15 Lys Lys Glu Thr Asn Gly His <210> 503 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 503 Lys Thr Asn Gly ser Lys Gly Val Lys Gly Glu Tyr Glu Lys Lys Lys 1 5 10 15 Glu Thr Asn Gly His <210> 504 <211> 16 <212> PRT <213> Plasmodium falciparum <400> 504 Lys Gly val Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 15 <210> 505 <211> 13 <212> PRT <213> Plasmodium falciparum <400> 505 Lys Gly Glu Tyr Glu Lys Lys Lys Glu Thr Asn Gly His 1 5 10 <210> 506 <211> 60 <212> PRT <213> Plasmodium falciparum <400> 506 Lys Thr lie Glu Lys lie Asn Lys Ser Lys Ser Trp Phe Phe Glu Glu 1 5 10 15 Leu Asp Glu lie Asp Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys 25 30 Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp val lie lie Asp 40 45 Asn Thr Glu lie Gin Lys lie He Arg Asp Tyr His 50 55 60 <210> 507 <211> 56 <212> PRT <213> Plasmodium falciparum - 166- 158109/1 <400> 507 Lys lie Asn Lys Ser Lys Ser Trp Phe Phe Glu Glu Leu Asp Glu l e l 5 10 15 Asp Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn 25 30 Lys Thr Lys Tyr Glu Arg Gly Asp al lie lie Asp Asn Thr Glu lie 40 45 Gin Lys lie lie Arg Asp Tyr His 50 55 <210> 508 <211> 39 <212> PRT <213> Plasmodium falc parum <400> 508 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp Val lie lie Asp Asn Thr Glu lie Gin 25 30 Lys lie lie Arg Asp Tyr His <210> 509 <211> 32 <212> PRT <213> Plasmodium falciparum <400> 509 His lie Met Leu Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys Ser ser Ser Ser Asn Lys Val His 25 30 <210> 510 <211> 35 <212> PRT <213> Plasmodium falciparum <400> 510 Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu 1 5 10 15 Arg Gly Asp Val lie lie Asp Asn Thr Glu lie Gin Lys lie lie Arg 25 30 Asp Tyr His <210> 511 <211> 32 <212> PRT <213> Plasmod um falciparum <400> 511 Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 - 167- 158109/1 val lie lie Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr His 25 30 <210> 512 <211> 29 <212> P T <213> Plasmodium falciparum <400> 512 Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp val lie lie 1 5 10 15 Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr His 25 <210> 513 <211> 48 <212> PRT <213> Plasmodium falciparum <400> 513 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp val lie lie Asp Asn Thr Glu lie Gin 25 30 Lys lie He Arg Asp Tyr His Thr Leu Asn val His Lys Leu Asp His 40 45 <210> 514 <211> 44 <212> PRT <213> Plasmodium falciparum <400> 514 Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu 1 5 10 15 Arg Gly Asp val lie lie Asp Asn Thr Glu lie Gin Lys lie lie Arg 25 30 Asp Tyr His Thr Leu Asn val His Lys Leu Asp His 40 <210> 515 <211> 41 <212> PRT <213> Plasmodium falciparum <400> 515 Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 Val lie lie Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr His 25 30 Thr Leu Asn Val His Lys Leu Asp His 40 <210> 516 <211> 38 - - 158109/1 <212> PRT <213> Plasmod um falciparum <400> 516 Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp val lie lie 1 5 10 15 Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr His Thr Leu Asn 25 30 Val His Lys Leu Asp His <210> 517 <211> 44 <212> PRT <213> Plasmod um falciparum <400> 517 Lys Pro Leu Ala Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys 1 5 10 15 Thr Lys Tyr Glu Arg Gly Asp val lie lie Asp Asn Thr Glu lie Gin 25 30 Lys lie He Arg Asp Tyr His Thr Leu Asn Val His 40 <210> 518 <211> 40 <212> PRT <213> Plasmodium falciparum <400> 518 Lys Leu Arg Lys Arg Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu 1 5 10 15 Arg Gly Asp Val lie lie Asp Asn Thr Glu lie Gin Lys lie He Arg 25 30 Asp Tyr His Thr Leu Asn val His 40 <210> 519 <211 37 <212> PRT <213> Plasmodium falciparum <400> 519 Lys Arq Glu Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu Arg Gly Asp 1 5 10 15 val lie lie Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr His 25 . 30 Thr Leu Asn Val H s <210> 520 <211> 34 <212> PRT <213> Plasmodium falciparum <400> 520 - 169- 158109/1 Lys Thr Gin lie Asn Lys Thr Lys Tyr Glu 'Arg Gly Asp val lie lie 1 5 . 10 15 Asp Asn Thr Glu lie Gin Lys lie lie Arg Asp Tyr Hi's Thr Leu Asn 25 30 Val His <210> 521 <211> 32 <212> PRT <213> Plasmodium falciparum <400> 521 His He Met Leu Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys ser Tyr Lys Lys Lys Ser Ser ser Ser Asn Lys val His ' 25 30 <210> 522 <2ll> 28 <212> PRT <213> Plasmodium falciparum <400> 522 Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser Cys Glu Cys Ser 1 5 10 15 Tyr Lys Lys Lys ser Ser Ser Ser Asn Lys Val His 25 <210> 523 <211> 18 <212> PRT <213> Plasmod um falciparum <400> 523 Lys Ser Cys Glu cys Ser Tyr Lys Lys Lys Ser Ser Ser ser Asn Lys 1 5 10 15 val His <210> 524 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 524 Lys Lys Lys Ser Ser Ser Ser Asn Lys val His 1 5 10 <210> 525 <211> 10 <212> PRT <213> Plasmodium falciparum <400> 525 Lys Lys Ser ser Ser Ser Asn Lys Val 1 5 <210> 526 - - 158109/1 <211> 9 <212> PRT <213> Plasmodium falciparum <400> 526 Lys Ser Ser Ser Ser Asn Lys Val 1 5 <210> 527 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 527 His l e Met Leu Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu cys Ser Tyr Lys Lys Lys ser Ser Ser Ser Asn Lys 25 30 <210> 528 <211> 24 <212> PRT <213> Plasmodium falciparum <400> 528 His lie Met Leu Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys Lys Lys . 20 <210> 529 <211> 23 <212> PRT <213> Plasmodium falciparum <400> 529 His lie Met Leu Lys ser Gin Met Tyr Thr Asn Glu Gly Asn Lys Ser 1 5 10 15 Cys Glu cys Ser Tyr Lys Lys <210> 530 <211> 22 <212> PRT <213> Plasmodium falciparum <400> 530 His lie Met Leu Lys Ser Gin Met Tyr Thr Asn Glu Gly Asn Lys ser 1 5 10 15 Cys Glu Cys Ser Tyr Lys <210> 531 <211> 36 <212> PRT <213> Plasmod fal ciparum <400> 531 His Asn Asn His Asn lie Gin lie Tyr Lys Asp Lys Arg lie Asn Phe 10 15 Met Asn Pro His Lys val Met Tyr His Asp Asn Met Ser Lys Asn Glu 25 30 Arg Thr Glu Lys <210> 532 <211> 30 <212> PRT <213> Plasmodium falciparum <400> 532 His Asn Asn His Asn lie Gin lie Tyr Lys Asp Lys Arg lie Asn Phe 1 5 10 15 Met Asn Pro His Lys val Met Tyr His Asp Asn Met Ser Lys 25 30 <210> 533 <211> 21 <212> PRT <213> Plasmodium falciparum <400> 533 His Asn Asn His Asn lie Gin lie Tyr Lys Asp Lys Arg lie Asn Phe 1 5 10 15 Met Asn Pro His Lys <210> 534 <211> 17 <212> PRT <213> Plasmodium falciparum <400> 5 4 His Lys val Met Tyr His Asp Asn Met Ser Lys Asn Glu Arg Thr Glu 1 5 10 15 Lys <210> 535 <211> 11 <212> PRT <213> Plasmodium falciparum <400> 535 His Lys Val Met Tyr His Asp Asn Met Ser Lys 1 5 10

Claims (9)

- 172 - 158109/2 CLAIMS:

1. An isolated influenza virus peptide consisting of 7 to about 50 amino acids with at least one lysine residue located on one end of the peptide and at least one lysine residue or at least one histidine residue located on the other end of the peptide, said peptide comprising: (a) a first lysine residue located six to ten residues from a second lysine residue; (b) at least one histidine residue; and (c) at least 6% lysine residues.

2. The isolated influenza virus peptide of claim 1 wherein the peptide is present in an emerging strain of influenza virus.

3. A therapeutic composition comprising the isolated influenza virus peptide of claim 1 and a pharmaceutically acceptable carrier or adjuvant.

4. The therapeutic composition of claim 3 wherein the peptide is conserved in a strain of influenza virus for at least two consecutive years including the current year.

5. A therapeutic composition comprising a plurality of isolated influenza virus peptides of claim 1, and a pharmaceutically acceptable carrier.

6. The therapeutic composition of claim 5 wherein at least one of the plurality of isolated influenza virus peptides of claim 1 is conserved in the influenza virus hemagglutinin amino acid sequence for at least two consecutive years including the current year.

7. An influenza virus vaccine comprising at least one isolated influenza virus peptide of claim 1 present in the hemagglutinin protein of an emerging strain of influenza virus and a pharmaceutically acceptable carrier or adjuvant.

8. The influenza virus vaccine of claim 7 wherein the vaccine comprises a plurality of isolated influenza virus peptides of claim 1. - 173 - 158109/1

9. The vaccine of claim 7 wherein the at least one isolated influenza virus peptide of claim 1 is conserved for at least two consecutive years in the emerging strain of influenza virus. For the Applicants, REINHOLD COHN AND PARTNERS By: