RU2793972C2 - Immunotherapeutic methods for treating and/or preventing lung cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention touches upon treatment and diagnosis of lung cancer and metastases thereof. Proposed is a pharmaceutical composition to be used in a method for therapeutic or preventive treatment or for diagnosing ZP3 protein expressing lung cancer and/or metastases thereof in humans. The composition contains a source of an immunogenic polypeptide comprising at least one of the MHC Class I and II-restricted epitopes from the amino acid sequence of human zona pellucida protein 3 (hZP3), and at least one excipient. The source of the immunogenic polypeptide includes at least one immunogenic peptide comprising or consisting of amino acid sequence SEQ ID NO: 83, a nucleic acid molecule encoding the said immunogenic polypeptide and/or an immunogenic polypeptide expressing cell.

EFFECT: diagnosis and treatment of primary and/or recurrent ZP3 protein expressing lung cancer and metastases thereof.

11 cl, 7 dwg, 6 tbl, 4 ex

Description

FIELD OF THE INVENTION

The present invention relates to the treatment and diagnosis of lung cancer and its metastases. More specifically, the invention relates to antigen sources providing at least the immunogenic portion of a cancer cell-associated protein, which is preferably the zona pellucida (ZP) protein, especially the ZP3 protein. Such antigen sources can be used in vaccines and pharmaceutical compositions for the therapeutic and prophylactic treatment of primary and/or recurrent lung cancer and its metastases.

BACKGROUND OF THE INVENTION

Lung cancer refers to malignant tumors originating from lung tissue that can originate in any part of the lung, although the vast majority (approximately 90-95%) of lung cancers are carcinomas, malignant neoplasms that arise from epithelial cells. There are two main types of lung carcinoma, classified by histopathological analysis into non-small cell (80.4%) and small cell (16.8%) lung carcinoma. Cancers can also arise from the pleura (called mesothelioma) or, rarely, from supporting tissues within the lungs, such as blood vessels. The main causes of any cancer are non-genetic factors such as exposure to carcinogens (eg, tobacco smoke, asbestos, arsenic, particulate matter), ionizing radiation, and viral infection. Epidemiological studies have shown that genetic factors may contribute to the risk of developing lung cancer.

Lung cancer is one of the most common malignant tumors. In 2007, lung cancer accounted for approximately 15% of all cancer diagnoses and 28% of all cancer deaths. It is the fourth most diagnosed cancer in men and women, but it is the number one cause of cancer death in men and women each year. Most cases of lung cancer are diagnosed at a late stage, which indicates a poor prognosis. Lung cancer is highly lethal, with a 5-year patient survival rate of only 14% in the United States. Treatment for lung cancer depends on the specific cell type of the cancer, metastases, and the condition of the patient. Common treatments include (combinations of) surgery, chemotherapy (eg, cisplatin, carboplatin, gemcitabine, paclitaxel, docetaxel, etoposide, vinrorelbin, topotecan, irrinotecan), radiation therapy, immunotherapy (eg, atezolizumab, nivolumab, pembrolizumab), and "targeted therapy". (eg, gefitinib, erlotinib, bevacizumab). A number of "targeting agents" are in the early stages of clinical development, such as cyclooxygenase-2 inhibitors, the apoptosis promoter exisulind, proteasome inhibitors, bexarotene, and the epidermal growth factor receptor inhibitor cetuximab.

Small cell lung carcinoma is initially treated with radiation and chemotherapy with cisplatin or etoposide, sometimes in combination with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, or irinotecan. Surgical treatment has no significant effect on survival in small cell lung carcinoma. In advanced small cell lung cancer, celecoxib can be combined with etoposide to improve outcomes.

Non-small cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC). NSCLC C accounts for about 85% of all lung cancers. As a class, NSCLC is relatively insensitive to chemotherapy compared to SCLC. When possible, they are mainly treated with curative intent surgical resection, although chemotherapy is increasingly being used both before surgery (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy). Currently, primary treatment for NSCLC includes surgery and chemotherapy with cisplatin or carboplatin, often in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine. Surgery is usually the only option for NSCLC, limited to one lung, up to stage IIIA. If surgery is no longer possible, primary chemotherapy is given.

While existing therapies offer some benefit in treating lung cancer, the outlook is still mostly poor, and there is still an absolute need to find treatments that are more effective and less toxic. The identification of new therapeutic targets for the treatment of lung cancer is a crucial step to achieve this goal.

Advances in molecular medicine have increased interest in tumor-specific antigens that can serve as targets for various immunotherapeutic strategies or strategies with small molecular weight compounds.

To serve as a suitable target for immunotherapeutic strategies against cancer, such antigens should be highly expressed in cancer tissues and ideally not in normal tissues. However, expression in tissues that are not essential for life may be acceptable.

The concept of treating ZP-expressing tumors by active immunization has been previously described in the art. For example, Rahman et al. (A novel treatment strategy for ovarian cancer based on immunization with zona pellucida protein (ZP) 3. FASEB J. 2012 Jan; 26 (1): 324-33) proves the principle of treatment of ovarian cancer in transgenic mice by identifying humoral and cellular vaccination against ZP3 proteins and cells expressing ZP3, respectively. In addition, active immunization with ZP proteins is a common practice in large wild animals as a sterilization method that demonstrates its feasibility and safety (see, for example, Gupta and Minhas, Frontiers In Bioscience, 2017, Scholar, 9, 357-374, http:/ /www.bioscience.org/2017/v9c/af/492/2.htm; Mask et al., 2015, Theriogenology; 84 (2): 261-267). Numerous studies indicate that decreased fertility was associated with antibody titers (Shresta et al., 2015, Vaccine 33, 133-140; Harris et al., 1999, Protein Expr Purif; 16 (2): 298-307; Martinez and Harris, 2000, J Reprod Fertil; 120 (1): 19-32). Additional degenerative ovarian pathologies have been described for immunization with recombinant ZP3 and ZP4, in particular (e.g., Govind et al., 2002, Vaccine 21, 78-88; Paterson et al., 1998, Am J Reprod Immunol 40, 198-209; and Srivastava et al., 2002, Reproduction 123, 847-857). In an autoimmune ovarian disease study, researchers demonstrated that oophoritis (damage to ovarian tissue) can be induced in mice by inducing a ZP3-specific CD4+ T cell response by vaccination with a 15 amino acid ZP3 polypeptide containing an MHC class II binding epitope. (Rhim et al., 1992, J. Clin. Invest. 89, 28-35). However, there are no reports of ZP protein expression in lung cancer.

The aim of the present invention is to create new immunotherapeutic strategies for the treatment and/or recurrent forms of lung cancer and its metastases.

SUMMARY OF THE INVENTION

The present inventors have surprisingly found that zona pellucida 3 (ZP3) proteins, especially the Zona pellucida 3 (ZP3) protein, are expressed in lung cancer cells and represent a suitable target for immunotherapeutic strategies in the treatment of lung cancer and its metastases, as well as in its diagnosis.

ZP3 is normally found in women in the so-called "zona pellucida", which forms the extracellular matrix surrounding the oocyte. This zona pellucida (zona pellucida) induces an acrosomal reaction in spermatozoa, determines species-specific fertilization, and prevents polyspermy in mammals. The zona pellucida contains four major glycoproteins, ZP1, ZP2, ZP3 and ZP4. For convenience, we will refer herein to zona pellucida or ZP proteins, by which is meant both glycosylated and non-glycosylated forms of zona pellucida, unless specifically noted otherwise.

The present invention is based on the discovery that lung cancer cells can exhibit significant ZP protein expression to the extent that immunotherapeutic strategies such as passive immunization, active immunization and targeted immunoconjugate therapy can be used to produce at least one of i) reducing the growth or size of primary tumors, ii) reducing the growth or size of metastases derived from them, iii) eradicating tumors, and iv) improving survival.

The present strategy is equally suitable for preventing metastasis of lung cancer as well as for preventing recurrence of lung cancer in previously treated individuals. Thus, it is understood that the terms “lung cancer cell” and “ZP-expressing lung cancer cell” also include such cells derived from lung cancer cells, since they can occur in other parts of the body other than the lungs, for example, as a result of metastasis. .

Example 4 herein describes a preclinical study of humanized HLA-A2 transgenic mice with hZP3-expressing tumors. Vaccination of these transgenic mice with hZP3 polypeptide (a/k 1-383) and hZP3 HLA-A2-restricted T cell epitopes induced CD8+ T cells. In addition, no increase in tumor size was observed, while tumor size increased in control mice treated with PBS.

Expression of the ZP protein in lung cancer cells has never been established before. Thus, there is no indication in the prior art that lung cancer cells can actually be the target of ZP-based immunotherapy. The present invention thus provides for the first time methods for treating lung cancer in an individual that target the ZP protein as a tumor-specific antigen. As will be understood by those skilled in the art based on the present disclosure, such treatments include passive immunization, active immunization, as well as targeted therapy using immunoconjugates.

These and other aspects of the present invention will be described in more detail below.

DETAILED DESCRIPTION OF THE INVENTION

A first aspect of the present invention relates to a method for the therapeutic and/or prophylactic treatment or diagnosis of primary and/or recurrent lung cancer and its metastases in an individual in need thereof, wherein the method comprises administering to said individual at least one of the following:

a source of an immunogenic polypeptide capable of inducing a cellular or humoral immune response against human zona pellucid protein (hZP), hZP3 or hZP3 (23-350);

a T cell containing a T cell receptor that binds to an MHC-peptide complex, where the peptide is a peptide from hZP and also from hZP3 or hZP3 (23-350);

an antibody or fragment thereof that specifically binds to hZP, or hZP3 or hZP3 (23-350); And

a genetic construct containing a nucleic acid sequence encoding the specified polypeptide or antibody, where the genetic construct is configured for delivery and expression in humans.

As used herein, the term "lung cancer" refers to primary and/or recurrent lung cancer, as well as its metastases, which can be localized anywhere in the body. Preferably, the present method is a method for treating malignant tumors derived from epithelial cells, such malignant tumors are also collectively referred to as carcinomas. More specifically, the invention relates to the treatment of NSCLC, which includes adenocarcinomas, squamous cell carcinomas and large cell carcinomas, as well as their metastases.

Generally, for the purposes of the present invention, the term "lung cancer" refers to malignant diseases or conditions and can be used interchangeably with certain other terms such as "(malignant) lung tumor" and "(malignant) neoplastic disease". Generally, for the purposes of the present invention, the term "lung cancer" does not include benign neoplasm and/or benign tumors. However, the present invention in its broadest sense may also cover the treatment of individuals suffering from such benign conditions in order to prevent the progression or development of malignant neoplasms (lung cancer). Lung cancer can be staged using the American Joint Committee on Cancer TNM (Tumor, Node, Metastases) classification as follows:

Stage I: the tumor is found in only one lung and has not spread to any lymph nodes;

Stage II: the tumor has spread to the lymph nodes that are contained in the environment of the lung;

Stage IIIa: The tumor has spread to lymph nodes outside the lung, in the trachea, including the chest wall and diaphragm on the same side that the cancer started.

Stage IIIb: The tumor has spread to lymph nodes in the opposite lung or in the neck;

Stage IV: The tumor has spread to other parts of the lungs or distantly throughout the body.

The aforementioned TNM staging system is not often used for patients with SCLC because in most cases metastatic disease is suspected or identified at the time of diagnosis. Survival in these patients is generally independent of minor differences in the extent of tumor involvement. Instead, most experts use a simple two-stage system created by the Veterans Council Lung Cancer Research Group. This system defines SCLC as a "limited" or "common" stage. The present method provides a significant response rate at all stages, and thus, in a broad sense, it concerns the treatment of lung cancer at any of the above stages.

The method of the invention may be a primary treatment or be used as adjunctive therapy before, during, or after the treatment of patients using any other method of treatment, including, for example:

operation;

radiation therapy;

chemotherapy, for example using platinum-based drugs such as cisplatin and carboplatin; nucleoside analogs such as gemcitabine; taxanes such as paclitaxel and docetaxel; topoisomerase I inhibitors such as topotecan and irinotecan; topoisomerase II inhibitors such as etoposide; and antimitotic drugs such as vinorelbine;

"targeted therapy", for example, using EGFR inhibitors such as gefitinib; tyrosine kinase inhibitors such as erlotinib; VEGF-A inhibitors such as bevacizumab; cyclooxygenase-2 inhibitors; cyclic guanosine monophosphate phosphodiesterase inhibitors such as exisulind; proteasome inhibitors; RXR agonists such as bexarotene; and EGFR inhibitors such as cetuximab;

immunomodulatory therapy, for example, as described below; And

their combinations.

The method according to the invention is preferably combined with immunomodulatory therapy. It is particularly preferred that when the method comprises administering a source of an immunogenic polypeptide capable of eliciting a cellular or humoral immune response against hZP, such method is combined with immunomodulatory therapy. The immunomodulatory therapy that may be combined with the method of the invention may be selected from one or more of the following:

the use of a checkpoint inhibitor such as, for example, an antibody against PD1, PDL1, CTLA4, TIM-3 and/or LAG-3;

the use of targeted delivery of antibodies to selected members of the TNF receptor family, such as, for example, an antibody against CD40, 4-1 BB, CD137, OX-40/CD134 and/or CD27;

the use of an immunosuppressive cytokine such as, for example, IL-10, TGF-β and/or IL-6;

the use of a γC cytokine such as, for example, IL-7, IL-15, and IL-21 and/or IL-2, since these cytokines have the ability to increase committed T cells;

the use of a TLR agonist such as, for example, described by Kaczanowska et al. (J Leukoc Biol. 2013 Jun; 93 (6): 847-863) and/or a TLR ligand as described herein below;

the use of an invariant natural killer T cell (iNKT) agonist, such as, for example, the synthetic iNKT agonist described by Cerundolo et al. (Curr Opin Immunol. 2010; 22 (3): 417-24).

The invention relates to methods that are suitably used for the treatment of primary lung cancer, recurrent lung cancer and its metastases, which is considered herein as "therapeutic treatment" or "radical treatment", as well as for preventing metastases and/or recurrence of lung cancer, optionally after or in combination with other therapies, such as those previously described, which is referred to herein as "prophylactic treatment".

For the methods of the invention, the subject to be treated is a human and may be male or female. When the subject to be treated is a (premenopausal) woman, the clinical efficacy of the method can be monitored by monitoring autoimmunity against ovarian tissue. For example, blood hormone levels can then be used as a biomarker for clinical performance and replace the clinical endpoint (PFS, OS) to reduce data output times.

The present invention is based on the detection of expression of ZP proteins by a malignant cell, which presents various options for immunotherapeutic strategies. However, since different tumors may have different or altered gene expression patterns, as will be appreciated by those skilled in the art, certain lung cancers may also occur that do not express ZP proteins to any significant extent. Thus, as a rule, the invention relates to the treatment of lung cancer or its metastases expressing ZP proteins, preferably ZP3.

The naming of the glycoprotein components of ZP has been quite controversial over the years and has used several criteria, including apparent molecular weight, protein sequence length, and identity comparisons, leading to confusing nomenclature. Harris et al. [(1994) DNA seq. 96: 829-834] proposed a unified nomenclature system in which ZP genes were named in order of the length of their encoded protein sequence from longest to shortest. Since the mouse ZP genes ranked in the order ZP2, ZP1, and then ZP3 by these criteria, a new system was introduced where ZP2 became ZPA, ZP1 became ZPB, and ZP3 became ZPC. More recently, Hughes et al [(1999) BBA-Gene Structure and Expression 1447: 303-306], among others, reported that the true human orthologue of the known mouse ZP1 gene is not ZPB, but that a separate human ZP1 gene exists. It is now generally accepted that there are four distinct (human) families of ZP glycoproteins - ZP1, ZP2, ZP3 and ZPB [cf. Lefievre et al (2004) Hum. reproduction. 19:1580-1586]. The ZPB glycoprotein is now also referred to as ZP4 according to this nomenclature. This nomenclature is used, for example, in the Uniprot/SWISSprot, ensEMBL, BLAST (NCBI), SOURCE, SMART, STRING, PSORT2, CDART, UniGene and SOSUI databases, all of which are involved in the Bioinformatic Harvester (http://harvester.embl.de ).

Accordingly, the terms ZP1, ZP2, ZP3, and ZP4 are used herein to refer to the four families of ZP glycoproteins, where ZP2, ZP3, and ZP4 correspond to ZPA, ZPC, and ZPB, respectively, according to the nomenclature proposed by Harris et al. More specifically, the terms hZP1, hZP2, hZP3, and hZP4 are used herein to refer to proteins having the polypeptide backbones listed in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 and SEQ ID NO. 4, respectively, and their allelic variants.

In accordance with the invention, the ZP protein is typically a ZP3 protein.

Allelic ZP variants that may occur naturally are also covered by the respective terms ZP and hZP. Allelic variants include, in particular, variants resulting from single nucleotide polymorphisms (SNPs). SNPs can fall into the coding sequences of genes, non-coding regions of genes, or into intergenic regions. SNPs within a coding sequence will not necessarily change the amino acid sequence of the protein that is being produced. A SNP in which both forms result in the same polypeptide sequence is called synonymous (sometimes called a silent mutation) - if a different polypeptide sequence is created, they are not synonymous. For a variant to be considered a SNP, it must occur in at least 1% of the population. In the context of the present invention, "allelic variants" may also include a variant polypeptide sequence resulting from (nonsynonymous) mutations, i.e. polypeptide variants resulting from point mutations, insertions, deletions, etc., occurring in less than 1% of a population.

Thus, in accordance with the present invention, the terms hZP1, hZP2, hZP3 and hZP4 include ZP proteins that differ from SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 and SEQ ID NO. 4, respectively, for minor modifications of the sequence. Such modifications, in non-limiting examples, include changes in one or more amino acids, including deletions (eg, a truncated version of the peptide), insertions, and/or substitutions.

By "allelic variant" is meant herein a variant that has at least 90%, preferably at least 95%, more preferably at least 97%, even more preferably at least 98% , even more preferably at least 99%, even more preferably at least 99.5% and most preferably at least 99.9% amino acid sequence identity with any of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 and SEQ ID NO. 4.

Each of the ZP proteins contains a signal peptide for targeting the protein along the secretory pathway, a zonal domain, and a transmembrane domain adjacent to the carboxyl terminus followed by a short cytoplasmic tail. In embodiments that involve administering an antibody or fragment thereof that specifically binds to hZP, the antibody or fragment thereof is directed against the extracellular domain of the ZP. In embodiments of the invention that relate to active immunization, as a source of an immunogenic polypeptide capable of inducing a cellular immune response against hZP, any part of the hZP that contains a T-cell epitope restricted by MHC class I and/or class II can in principle be used.

The amino acid sequence of the resulting hZP3 protein contains an N-terminal signal peptide sequence (amino acid positions 1-22 in SEQ ID NO: 3), a conserved "ZP extracellular domain" (amino acid positions 23-350 in SEQ ID NO: 3), and a pro-peptide (amino acid positions 351-424 of SEQ ID NO: 3) consisting of a consensus furin cleavage site (CFCS; amino acid positions 351-352 of SEQ ID NO: 3) blocking the polymerization of an outer hydrophobic region (EHP) and a C-terminal transmembrane domain (amino acid positions 353-424 in SEQ ID NO: 3). The hZP3 signal peptide is cleaved during translation and CFCS cleavage separates the extracellular domain of the mature hZP3 protein (consisting of amino acid positions 23-350 in SEQ ID NO: 3) from the EHP, allowing it to be incorporated into the nascent ZP filaments. Thus, the amino acid backbone of the extracellular domain of mature hZP3 has an amino acid sequence consisting of amino acid positions 23-350 in SEQ ID NO: 3 of hZP3. This extracellular domain fragment is referred to herein as hZP3 (23-350) (SEQ ID NO: 5).

In a preferred embodiment, the present invention relates to a method of treating lung cancer and its metastases in an individual by active immunization. An active immunization method involves administering a source of an immunogenic polypeptide capable of inducing a cellular immune response against hZP3 or against cells expressing (any part of) hZP3 and/or a humoral immune response against hZP3 or hZP3 (23-350).

The source of the immunogenic polypeptide may be a protein source, a nucleic acid, or a combination thereof. The protein source may, for example, be a composition comprising one or more peptides, polypeptides, or proteins that act as an immunogen. Alternatively, the source of the immunogenic polypeptides may be a nucleic acid molecule encoding one or more immunogenic peptides, polypeptides, or proteins, which, when administered to the individual being treated, expresses the immunogenic peptides, polypeptides, or proteins. The nucleic acid molecule may be DNA, cDNA, RNA, mRNA, a variant thereof, a fragment thereof, or a combination thereof, as, for example, described in WO2014/165291 and WO2013/087083. The source of the immunogenic polypeptide may further be a cell, preferably a living cell, that expresses the immunogenic polypeptide or presents an epitope of the immunogenic polypeptide. Preferably, the cell is microbial, more preferably bacterial, such as, for example, live attenuated Listeria monocytogenes, such as described in WO 2015/164121. Alternatively, the cellular source of the immunogenic polypeptide of the invention is an autologous or allogeneic dendritic cell that presents at least one epitope of the immunogenic polypeptide in an HLA molecule on its surface.

In a preferred embodiment, the immunogenic polypeptide comprises a contiguous amino acid sequence selected from the amino acid sequence of the ZP protein, where the contiguous amino acid sequence preferably contains at least one of MHC class I and class II restricted T cell epitopes. More preferably, the immunogenic polypeptide comprises a contiguous amino acid sequence selected from the amino acid sequence of the hZP3 protein (i.e., SEQ ID NO: 3), where the contiguous amino acid sequence preferably contains at least one of the T-cell epitopes restricted by the MHC class I and class II, for example, selected from tables 2, 3 and 5, respectively. More preferably, the contiguous amino acid sequence contains at least one of MHC class I and MHC class II restricted T-cell epitopes with a low percentile rank (see Moutaftsi et al., Nat Biotechnol. 2006 Jul; 24(7 ): 817-9 and Kotturi et al., J Virol 2007 May 81 (10): 4928-40). An MHC class I restricted T-cell epitope with a low percentile rank is an epitope with a percentile rank that does not exceed 1.00, 0.80, 0.40, 0.30, 0.20, 0.15, 0 .10 or 0.05 (see, for example, tables 2 and 5). An MHC class II restricted T-cell epitope with a low percentile rank is an epitope with a percentile rank that does not exceed 2.50, 2.40, 2.05, 2.00, 1.80, 1.60, 1 .40, 1.20, 1.10, 1.00, 0.90, 0.70, 0.60, 0.50, 0.40, 0.20. 0.15, 0.10, 0.05 or 0.02. Preferably, the contiguous amino acid sequence is selected from an amino acid sequence from the group of amino acid sequences from hZP3 proteolytic fragments consisting of an N-terminal signal peptide sequence (positions 1-22 in SEQ ID NO: 3), a mature extracellular domain sequence (positions 23-350 in SEQ ID NO: 3, i.e. SEQ ID NO: 5), and the propeptide sequence (amino acid positions 351-424 in SEQ ID NO: 3). Examples of such contiguous amino acid sequences are shown in Figure 4 and combinations of such contiguous amino acid sequences are shown in Table 4.

The continuous amino acid sequence from the hZP(3) protein contained in the immunogenic polypeptide contains an immunologically active (sequence) fragment of the hZP(3) protein. The term "immunologically active fragments thereof" is generally understood in the art to refer to an antigen fragment of the hZP(3) protein containing at least an epitope, meaning that the immunogenic polypeptide at least includes 4, 5, 6, 7. or 8 continuous amino acids from the hZP protein antigen sequence (3). According to the present invention, the fragment contains at least a MHC class I or MHC class II binding peptide presented by such an MHC molecule to the immune system. An "immunologically active fragment" of the present invention includes 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 contiguous amino acids from a ZP protein antigen sequence or a homologue or analog thereof. While most MHC-binding peptides are 9 amino acids long, longer peptides can be accommodated by the convexity of their core (Guo et al., 1992, Nature; 360 (6402): 364–366; Speir et al. . , 2001, Immunity; 14 (1): 81–92), resulting in binding of peptides 8 to 15 amino acids long (Schumacher et al., 1991, Nature; 350 (6320): 703–706). Examples of peptides in the hZP3 sequence that bind MHC class I are shown in Tables 2 and 5. Peptides that bind to class II proteins are not limited in size (Nelson et al., 1999, Rev Immunogenet; 1 (1): 47–59; Yassai et al., 2002, J Immunol; 168 (3): 1281-1285) and can vary from 11 to 30 amino acids in length (Rammensee 1995, Immunogenetics; 41 (4): 178-228), even whole proteins are possible. However, the binding motif is about 9 amino acids long. MHC class II can accommodate much longer peptides than MHC class I because the ends of the MHC II binding groove are open, thus the epitope (binding in the groove) can be surrounded by additional patches of amino acids at either end. Examples of peptides in the hZP3 sequence that bind MHC class II are shown in Table 3. An even more preferred fragment includes an epitope for both a cytotoxic T-lymphocyte (CTL) and a helper T-lymphocyte (CTL). However, the most preferred fragment is a peptide that requires processing by the antigen presenting cell, i.e. the fragment is at least about 18 amino acids in length, which is not necessarily a contiguous sequence from the hZP protein antigen (3).

The length of the contiguous amino acid sequence from the hZP(3) protein constituting the immunogenic polypeptide, or the length of the immunogenic polypeptide itself, is thus preferably at least 18, 19, 20, 21, 22, 25, 27, 30, 33 or 35 amino acids and preferably no more than 100, 80, 60, 50, 45, 40, 35, 33 or 30 amino acids. Preferably, the length of the contiguous amino acid sequence from the hZP(3) protein constituting the immunogenic polypeptide, or the length of the immunogenic polypeptide itself, is 19-50 or 19-45, more preferably 25-40 amino acids, even more preferably 25-35 and most preferably 25 -30 amino acids. From a workability point of view, an immunogenic polypeptide with a length of about 25 amino acids is optimal, while it is long enough to contain several epitopes and allow presentation by antigen-presenting cells. Suitable examples of such immunogenic polypeptides comprising a contiguous amino acid sequence from the hZP3 protein, each containing one or more MHC class I and/or MHC class II binding peptides, are shown in Figure 4.

The terms "their homologues", as used herein, refer to polypeptides that differ from the natural polypeptide by minor modifications, but which maintain the structure of the main polypeptide and the side chain of the natural form. Such changes include, but are not limited to, changes in one or more amino acid side chains; changes in one or more amino acids, including deletions (eg, a truncated version of the peptide), insertions and/or substitutions; changes in the stereochemistry of one or more atoms; and/or minor derivatizations including, but not limited to, methylation, glycosylation, phosphorylation, acetylation, myristoylation, prenylation, palmitation, amidation, and/or the addition of glycosylphosphatidylinositol. As used herein, a homologue or analog has either enhanced or substantially similar functionality as compared to a natural polypeptide. Typically, when optimally aligned, such as with the GAP or BESTFIT programs using default parameters, a natural polypeptide and its homologue share at least a certain percentage of sequence identity. GAP uses the Needleman and Wunsch global alignment algorithm to align two sequences over their entire length, maximizing the number of matches and minimizing the number of gaps. In general, the default GAP parameters are applied with gap creation penalty = 8 and gap extension penalty = 2. For proteins, the default scoring matrix is Blosum62 (Henikoff & Henikoff, 1992, PNAS 89, 915-919). Sequence alignment and percent sequence identity scores can be determined using computer programs such as GCG Wisconsin, version 10.3, available from Accelrys Inc., 9685 Scranton Road, San Diego, CA 92121-3752, USA. Alternatively, the percentage of similarity or identity can be determined by searching databases such as FASTA, BLAST, etc.

A homologue is herein understood to mean an immunogenic polypeptide having at least 70%, preferably at least 80%, more preferably at least 90%, even more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99% amino acid sequence identity with the naturally occurring ZP polypeptides mentioned above and still capable of eliciting at least the resulting immune response. The homologue or analog herein may contain substitutions, insertions, deletions, additional N- or C-terminal amino acids, and/or additional chemical groups such as carbohydrates to improve stability, solubility, and immunogenicity.

The invention explicitly includes the use of an immunogenic polypeptide comprising proteins that are homologous to the wild-type hZP(3) protein but differ from it by tumor-specific mutations (which may be patient-specific or common) that result in altered amino acid sequences, i.e. e. so-called neoantigens.

In accordance with the present invention, the immunogenic polypeptide that is administered to a human according to the present method may be a protein or glycoprotein or contain a protein or glycoprotein, be a cleavage product of a protein or glycoprotein and/or fragments thereof, which may be in a purified form or may be contained within a crude composition, preferably of biological origin, such as lysates, sonicates or fixates from prokaryotic or eukaryotic cell lines. Moreover, an immunogenic polypeptide is or contains chemically synthesized (poly)peptides or (poly)peptides that have been produced enzymatically in vitro , which may be in purified form or may be contained in a crude composition.

As used herein, the term "epitope" refers to the portion of an antigen, typically defined by a short peptide, that is capable of eliciting a cellular or humoral immune response when presented in a physiologically appropriate context in vivo . A "T cell epitope" refers to a short peptide, or portion thereof, that binds to MHC molecules and is recognized by certain T cells when presented in a certain MHC fragment. The T-cell epitope is capable of inducing a cell-mediated immune response by direct or indirect presentation of MHC molecules in the heterodimeric membrane. Preferably, in an immunogenic polypeptide, at least one MHC class II restricted epitope and an MHC class I restricted epitope are present within a contiguous sequence from the amino acid sequence of the hZP(3) protein, whereby it is preferred that the epitopes MHC class II restricted epitopes and at least one MHC class I restricted epitope selected from Tables 3, 2 and 5, respectively. For the sake of clarity, the peptide of the invention preferably includes at least one epitope presented by an MHC class I as well as at least one epitope presented by an MHC class II. Each of these epitopes can be presented and will bind to the respective specific MHC molecules present on cells after being processed as described herein. Thus, each MHC-restricted epitope may also be referred to as an MHC-binding and/or MHC-presenting epitope. Preferably, the specific proteasome cleavage site that creates the C-terminus of such an epitope is present exactly after the amino acid sequence of the epitope in order to be freed from the immunogenic polypeptide and presented on the MHC class I molecule. The length requirements are much less stringent for MHC class II epitopes, therefore the need for precise enzymatic generation of a class II binding peptide is less certain. Briefly, MHC molecules preferentially bind certain amino acid residues known as "anchor" residues (K. Falk et al., Nature 351: 290-96 (1991)). This feature allows recognition of class I and II MHC binding motifs in any known peptide sequence (see, for example, tables 2, 5 and 3).

In the present context, the term "MHC-restricted epitope" is synonymous with T-cell epitope. As used herein, the term "class I MHC restricted epitope" refers to a peptide recognized by cytotoxic T lymphocytes (also referred to as CD8+ cells, TCD8 or CTLs) in association with MHC class I. As used herein, the term “class II MHC-restricted epitope” refers to a peptide recognized by helper T cells (also referred to as CD4+ cells, TCD4 or CTL) in association with a class II MHC. A "B-cell epitope" is a portion of an antigen that is capable of binding to the antigen-binding site of an immunoglobulin and thus capable of stimulating a humoral response without being presented by an MHC molecule. As previously explained herein, a polypeptide suitable for the present invention, or a nucleic acid encoding said polypeptide, includes at least one T-cell epitope. However, the use of polypeptides that also contain a B cell epitope is not excluded from the present invention. Such immunogenic polypeptides may also include multiple T-cell and optionally a B-cell epitope. When multiple epitopes are present in a peptide, they may be oriented in tandem or in a nested or overlapping configuration, where at least one amino acid residue may be used by two or more epitopes.

The immunogenic polypeptide of the invention preferably comprises one or more class I MHC-restricted epitopes. As generally known to those skilled in the art, an antigen containing a single MHC-restricted epitope will only be useful in treating a (small) subgroup of patients who express the MHC allele. capable of binding that particular peptide. It is estimated that in humans, vaccines containing CTL epitopes restricted to HLA-A1, -A2, -A3, -A24 and -B7 can cover approximately 80% of individuals of most ethnic groups. Thus, when the present method is used to treat a human, it is particularly preferred that the method comprises administering a composition comprising one or more different polypeptides comprising one, more preferably two, most preferably three MHC class I binding epitopes from native ZP, preferably hZP3, selected from epitopes restricted by HLA-A1, HLA-A2, HLA-A3, HLA-A24 and HLA-B7; or their homologues.

In another embodiment, the immunogenic polypeptide of the invention preferably comprises one or more class II MHC restricted epitopes. The most commonly occurring class II MHC allele products in humans include HLA-DR1, -DR3, -DR4, and -DR7. Thus, preferably, the method comprises administering a composition comprising one or more different polypeptides comprising one, more preferably two, most preferably three MHC class II binding epitopes from native ZP, preferably hZP3, selected from HLA-DR1-restricted epitopes. , HLA-DR3, HLA-DR4 and HLA-DR7; or their homologues.

In another embodiment, the method of the invention comprises administering a composition comprising one or more polypeptides comprising one or more MHC class I restricted epitopes and one or more MHC class II restricted epitopes as described above and/or in the tables above. 2, 5 and 3, respectively; or their homologues. Even more preferably, said composition comprises an effective amount of one or more different polypeptides which together comprise essentially all of the MHC class I and II binding epitopes contained in one of the native ZP glycoproteins, preferably hZP3; or homologues of said one or more polypeptides.

In a preferred embodiment, the present method comprises administering a composition containing one or more immunogenic peptides. Preferably, said one or more different polypeptides together comprise at least 50%, more preferably at least 70%, even more preferably at least 80%, more preferably at least 90% and most preferably at least 95% of the MHC class I and MHC class II restricted epitopes contained in native ZP, preferably hZP3 or hZP3 (23-350) or homologues of said one or more polypeptides.

In a preferred embodiment, the present method comprises administering a composition comprising one or more immunogenic peptides selected from the peptides shown in Figure 4, such as immunogenic peptides comprising or consisting of an amino acid sequence from one or more of SEQ ID NOs: 66-75. Thus, the composition may comprise one of the immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 66-75. Preferably, however, the composition contains a combination of at least two immunogenic peptides containing or consisting of an amino acid sequence selected from SEQ ID NO. 66-75. In particular, the composition contains a combination of immunogenic peptides containing or consisting of an amino acid sequence selected from the sequence combinations listed in Table 4, or a combination of all 10 of SEQ ID NO. 66-75.

In a further preferred embodiment, the present method comprises administering a composition comprising one or more immunogenic peptides comprising or consisting of an epitope selected from the epitopes shown in Table 5, ie. SEQID NO. 76-85. The composition thus may include one of the immunogenic peptides containing or consisting of an amino acid sequence selected from SEQ ID NO. 76-85. Preferably, however, the composition contains a combination of at least two immunogenic peptides containing or consisting of an amino acid sequence selected from SEQ ID NO. 76-85. In particular, the composition contains a combination of immunogenic peptides containing or consisting of an amino acid sequence selected from combinations of sequences listed in Table 6, or a combination of all 10 of SEQ ID NO. 76-85. A particularly preferred composition comprises one or more or all of the immunogenic peptides comprising or consisting of the amino acid sequences from SEQ ID NO. 79, 80, 81, 83 and 84.

In a preferred embodiment, the present method comprises administering a source of immunogenic polypeptide, wherein the polypeptide contains at least 50%, more preferably at least 70%, even more preferably at least 80%, even more preferably at least 90% and most preferably at least 95% of the total amino acid backbone of native ZP glycoprotein, preferably hZP3 or hZP3(23-350); or a homologue of said polypeptide.

In a particularly preferred embodiment, the present method comprises administering a composition comprising a source of an immunogenic polypeptide, wherein the polypeptide comprises 90%, 95%, 97%, 98%, 99%, or 100% of the total amino acid backbone of the native ZP extracellular domain, namely hZP3 or hZP3 (23-350) or a homologue of said polypeptide. Such immunogenic polypeptides, as previously defined herein, may be glycosylated. Without wishing to be bound by theory, we hypothesize that by glycosylation of these polypeptides, their immunogenicity, at least to the extent that they elicit a humoral response (B cell response), is increased. Thus, an immunogenic polypeptide, as defined hereinbefore, is glycosylated, with a carbohydrate content in the range of 10-80, 15-70, or 20-60% by weight, based on the total weight of the glycoprotein or glycosylated polypeptide. Preferably, said glycosylated immunogenic polypeptide comprises a glycosylation pattern similar to that of the corresponding natural human ZP glycoprotein region.

In another particularly preferred embodiment, the method comprises administering a source of immunogenic polypeptide which is a composition comprising an effective amount of a plurality of different overlapping polypeptide fragments of native ZP, hZP3 or hZP3 (23-350) glycoprotein, wherein the length of the different overlapping polypeptide fragments is between 18 up to 60 amino acids, and together they comprise at least 50%, more preferably at least 70%, even more preferably at least 80%, even more preferably at least 90%, and most preferably at least 95% of the total amino acid backbone of said native ZP or the extracellular domain of said native ZP, hZP3 or hZP3 (23-350) or homologues of said polypeptides. More preferably, the different overlapping polypeptide fragments are 25-40 amino acids in length, even more preferably 25-35 and most preferably 25-30 amino acids. Generally, the amino acid sequence overlaps between different consecutive 18-60 amino acid polypeptide fragments for at least seven amino acids, preferably at least eight amino acids, more preferably at least nine amino acids, and most preferably, at least ten amino acids.

MHC binding motifs for the most common MHC class I and II alleles are described. These motifs detail the amino acid residues that serve as MHC binding anchors for specific MHC class I and II alleles. Complex computer algorithms are used to predict and quantify peptide/MHC binding affinity, which take into account the MHC binding anchors as well as the amino acid sequence of the peptide. Thus, from the input of a known amino acid sequence of the zona pellucida, these algorithms enumerate all potential T-cell epitopes, each with their respective predictor of binding (see, for example, Tables 2, 5, and 3). Well-known bioinformatics tools for this purpose include, for example, HLA_BIND (Parker et al., 1994, J. Immunol. 152: 163), SYFPEITHI (Rammensee et al., 1995, Immunogenetics 41, 178-228; Rammensee et al., Landes Bioscience 1997, international distributor: Springer Verlag GmbH & Co. KG, Heidelberg, Germany; http://www.syfpeithi.de/), NetMHC (Buus et al., 2003, Tissue Antigens., 62: 378-84; Nielsen et al ., 2003, Protein Sci., 12: 1007-17; Nielsen et al., 2004, Bioinformatics, 20 (9): 1388-97; http://www.cbs.dtu.dk/services/NetMHC/), TEPITOPE 2000 (Sturniolo et al., 1999, Nature Biotechnology 17, 555-562; http://www.vaccinome.com/pages/597444/), and (constantly updated) IEDB analysis resources - T cell epitope prediction tools: http://tools.iedb.org/main/tcell/.

Alternatively, those skilled in the art will be able to determine CTL and CTL binding epitopes experimentally using standard experiments (Current Protocols in Immunology, Wiley Interscience 2004). In a preferred embodiment, the method comprises administering a composition comprising an effective amount of a plurality of polypeptide fragments of 18 to 100 amino acids in length from a native ZP, hZP3 or hZP3(23-350) glycoprotein, wherein each polypeptide fragment contains one or more of said predicted potential epitopes restricted MHC class I or MHC class II. Preferably, the amino acid sequence of said predicted potential epitopes restricted by MHC class I or MHC class II does not overlap in different polypeptide fragments. Preferably, the plurality of different polypeptide fragments together represent at least 50%, 70%, 80%, 90%, or 95% of the potential MHC class I or MHC class II epitopes predicted by one or more of the above bioinformatics tools.

In some cases, it has been observed that the same peptide can bind to multiple MHC I or II allelic products (see, for example, Tables 2, 5 and 3). In one embodiment, the use of such "random" MHC binding peptides in the present method is particularly preferred.

The present immunization method preferably comprises administering a source of immunogenically active polypeptide fragments, said polypeptide fragments being selected from the zona pellucida protein fragments and/or their homologues as previously defined herein, said polypeptide fragments containing CTL and/or CTL epitopes restricted in the order HLA molecules, and these fragments are 18 to 45 amino acids in length. Peptides of 18 to 45 amino acids in length have been found to provide excellent immunogenic properties, as described in WO 02/070006. Peptides can preferably be chemically synthesized and optionally can (partially) overlap and/or can be ligated to other molecules, peptides or proteins. It may also be advantageous to add chemical groups or additional (modified or D-) amino acids to the amino or carboxy terminus of the peptide to increase stability and/or reduce the biodegradability of the peptide. Composite groups can be added to improve immunogenicity/immunostimulatory properties, for example by lipidation, extension and/or conjugation (see below). For example, a peptide can be extended by adding charged or polar amino acids to increase its solubility and/or increase its in vivo stability.

For purposes of immunization, the above immunogenic polypeptides of the invention may also be fused to proteins such as, but not limited to, tetanus toxin/toxoid, diphtheria toxin/toxoid, or other carrier molecules. The polypeptides of the invention can also be preferably fused to heat shock proteins such as recombinant endogenous (mouse) gp96 (GRP94) as a carrier for immunodominant peptides as described in (references: Rapp UK and Kaufmann SH, Int Immunol. 2004 Apr; 16 (4: 597-605; Zugel U, Infect Immun. 2001; 69 (6): 4164-7) or Hsp70 fusion proteins (Triebel et al.; WO99/54464) The immunogenic polypeptides of the invention can also be conjugated to molecules having adjuvant activity as indicated below, in particular with the TLR ligands/agonists listed below.

The individual amino acid residues of the present immunogenic (poly)peptides of the invention may be incorporated into a peptide via a peptide bond or a peptide bond mimetic. The peptide bond mimetic of the invention includes peptide backbone modifications well known to those skilled in the art. Such modifications include modifications to the amide nitrogen, α-carbon, amide carbonyl, complete replacement of the amide bond, extensions, deletions, or backbone cross-links. See mainly Spatola, Chemistry and Biochemistry of Amino Acids, Peptides and Proteins, Vol. VII (Weinstein ed., 1983). Several modifications of the peptide backbone are known, including ψ [CH ₂ S], ψ [CH ₂ NH], ψ [CSNH ₂ ], ψ [NHCO], ψ [COCH ₂ ], and ψ [(E) or (Z) CH=CH ]. The nomenclature used above follows that proposed by Spatola above. In this context, ψ indicates the absence of an amide bond. The structure that replaces the amide group is shown in parentheses.

Amino acid mimetics may also be included in the polypeptides. An "amino acid mimetic" is a non-natural amino acid constituent group that serves conformationally and functionally as an amino acid substitution in a polypeptide of the present invention. Such a composite group serves as a substitute for an amino acid residue if it does not interfere with the ability of the peptide to elicit an immune response against T-cell epitopes of the native ZP protein. Amino acid mimetics can include non-protein amino acids such as β-, γ-, δ-amino acids, β-, γ-, δ-imino acids (such as piperidine-4-carboxylic acid), as well as many derivatives of L-α-amino acids. A number of suitable amino acid mimetics are known to those skilled in the art and include cyclohexylalanine, 3-cyclohexylpropionic acid, L-adamantyl alanine, adamantylacetic acid, and the like. Peptide mimetics suitable for the peptides of the present invention are discussed in Morgan and Gainor, (1989) Ann. Repts. Med. Chem 24:243-252.

In a preferred embodiment, the present method comprises administering a composition comprising one or more of these immunogenic polypeptides, as defined herein, and at least one excipient. Excipients are well known in the art of pharmacy and, for example, can be found in textbooks such as Remington's Pharmaceutical Sciences, Mack Publishing, 1995.

In another preferred embodiment, the source of the immunogenic polypeptide of the invention that can be administered is a nucleic acid molecule encoding the immunogenic polypeptide. A source or composition containing a nucleic acid molecule encoding an immunogenic polypeptide may contain one or more different nucleic acid molecules encoding any of the immunogenic polypeptides, polypeptide fragments and/or peptides as defined herein above. In addition, the nucleic acid molecule can encode most of the native ZP protein. The nucleic acid molecule may, for example, encode a polypeptide containing at least 50%, 70%, 80%, 90%, 95% or 100% of the total amino acid backbone of a ZP, hZP3 protein, more preferably hZP3 (23-350) or a homologue of said polypeptide. Preferably, the nucleic acid molecule encodes a contiguous stretch of at least 50%, 70%, 80%, 90%, 95% or 99% of the complete amino acid backbone. It is also possible that the nucleic acid molecule encodes more than one (containing a T-cell epitope) immunologically active fragment of contiguous amino acid sequences from hZP(3), as defined herein above, resulting in different immunologically active fragments in the encoded amino acid sequences being separated by a spacer or linker in the form of beads on a string.

The nucleic acid molecule encoding the immunogenic polypeptide of the invention may be a DNA molecule, preferably a genetic construct, wherein the nucleotide sequence encoding the immunogenic polypeptide (cDNA) is operably linked to an appropriate expression control sequence allowing functional expression of the immunogenic polypeptide in target cells of a human subject, for example, including at least a strong (eg, viral) promoter. Genetic constructs for use as DNA vaccines, including, for example, plasmids or viral vectors, among others, are described in WO2014/165291, WO2016/123285 and WO2017/136758. Alternatively, the nucleic acid molecule encoding the immunogenic polypeptide of the invention may be an RNA molecule, such as mRNA, ssRNA, dsRNA, or combinations thereof. An RNA molecule may, for example, be formulated into a particle containing the molecule. Suitable embodiments of RNA-based vaccines are, for example, those described in WO2013/087083.

Routes of administration of nucleic acid vaccines include, but are not limited to, intramuscular, intranasal, intraperitoneal, intradermal, subcutaneous, intravenous, intraarterial, intraocular, and oral, as well as topical, transdermal, by inhalation or suppository, or into mucosal tissue such as vaginal lavage. , rectal, urethral, buccal and sublingual tissue. Preferred routes of administration include intramuscular, intraperitoneal, intradermal and subcutaneous injection. Genetic constructs can be introduced by methods including, but not limited to, electroporation methods and devices, conventional syringes, needleless injection devices, or "ion gun microparticle bombardment".

The source of the immunogenic polypeptide of the invention may further be a living cell that expresses and/or presents the immunogenic polypeptide. The cell may be an autologous or allogeneic immune cell, eg a dendritic cell, obtained from the individual to be treated, or the cell may be a microbial cell, more preferably bacterial, eg a live attenuated Listeria monocytogenes . The expressed immunogenic polypeptide is preferably an immunogenic polypeptide as defined in the document above. The immunogenic polypeptide can be expressed as part of a fusion protein, where preferably the immunogenic polypeptide is fused to a protein that is endogenous to the organism, such as the N-terminal fragment of L. monocytogenes LLO or the ActA protein. Suitable embodiments of the Listeria vaccine are, for example, described in WO 2015/164121. A bacterium expressing an immunogenic polypeptide of the invention may be administered orally or parenterally, preferably intravenously.

In another embodiment, the source of the immunogenic polypeptide of the invention is an autologous or allogeneic dendritic cell (DC) that presents at least one MHC-restricted epitope of the immunogenic polypeptide in an HLA molecule on its surface. Such dendritic cells, for example, can be obtained ex vivo by contacting and/or loading DC from the patient's blood, for example DC isolated from mononuclear cells in a patient/individual, with a composition containing the immunogenic polypeptides of the invention. An immunogenic polypeptide contacting mononuclear cells or DCs is an immunogenic polypeptide as defined herein above. You can use a pharmaceutical preparation to facilitate the collection of DC, such as Progenipoietin ^TM (Monsanto, St. Louis, Mo.) or GM-CSF/IL-4. After priming DC with peptides and washing to remove unbound peptides, DC is re-infused into the patient. In this embodiment, a composition is provided containing peptide-primed DCs that present sensitizing peptide epitopes in HLA molecules on their surface. Alternatively, instead of using autologous cells derived from an individual, allogeneic DCs can be used that are derived from a human dendritic cell progenitor line and designed to deliver tumor-associated antigens, such as, for example, those described in WO2009/019320, WO2014/090795 and WO2014 /006058. Methods for inducing an immune response using ex vivo peptide-primed DCs are well known to those skilled in the art.

The present immunization method may further comprise administering, preferably co-administering, at least one adjuvant. Adjuvants may include any adjuvant known in the art of vaccination and may be selected using textbooks such as Current Protocols in Immunology, Wiley Interscience, 2004.

As used herein, adjuvants are meant to include any substance or compound which, when used in combination with an antigen to immunize a human or animal, stimulates the immune system, thereby provoking, enhancing, or facilitating an immune response to the antigen, rather than generating a specific immune response to the adjuvant itself. . Preferred adjuvants enhance the immune response against a given antigen by at least 1.5, 2, 2.5, 5, 10, or 20 times the immune response generated against the antigen under the same conditions but in the absence of an adjuvant. Tests to determine the statistical mean enhancement of the immune response against a given antigen produced by an adjuvant in a group of animals or humans compared to a control group are available in the art. The adjuvant is preferably capable of enhancing the immune response against at least two different antigens. The adjuvant of the invention will generally be a compound foreign to humans, thereby excluding immunostimulatory compounds that are endogenous in humans, such as, for example, interleukins, interferons and other hormones.

A number of adjuvants are well known to the person skilled in the art. Suitable adjuvants include, for example, granulocyte-macrophage colony stimulating factor (GM-CSF), incomplete Freund's adjuvant (IFA), Montanide™ ISA-51, Montanide™ ISA 720 (adjuvants manufactured by Seppic, France), alpha-galactosylceramide, alum, aluminum phosphate, aluminum hydroxide, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-MDP), N- acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1'-2'-dipalmitoyl-sn-glycero-3-hydroxy-phosphoryloxy)-ethylamine (CGP 19835A, referred to as MTP-PE), DDA ( 2 dimethyldioctadecylammonium bromide), polyI:C, poly-A-poly-U, RIBI™, GERBU™, Pam3™, Carbopol™, Specol™, Titermax™, tetanus toxin, diphtheria toxoid, meningococcal outer membrane proteins, diphtheria protein CRM197. Preferred adjuvants contain a ligand that is recognized by the toll-like receptor (TLR) present on antigen-presenting cells. Various TLR-recognized ligands are known in the art and include, for example, lipopeptides (see, for example, WO 04/110486), lipopolysaccharides, peptidoglycans, lipteichoic acids, lipoarabinomannans, lipoproteins (from mycoplasmas or spirochetes), double-stranded RNA (poly I:C), poly ICLC (Hiltonol ^TM , manufactured by Oncovir, Inc., USA), unmethylated DNA, flagellin, CpG-containing oligonucleotides, Pam3CysSK4 and imidazoquinolines, as well as chemically modified derivatives of these ligands. The use of poly I:C is particularly preferred.

For therapeutic use, the present immunogenic polypeptides, nucleic acid sequences encoding them, cells expressing or presenting them, or present compositions comprising these polypeptides, nucleic acid sequences or cells, are administered to a patient suffering from lung cancer and possibly metastases, or a patient who has received other lung cancer treatments previously described herein in an amount sufficient to induce a primary autoimmune response directed against native ZP glycoproteins and tissue cells expressing ZP proteins. An amount sufficient to achieve this goal is defined as a "therapeutic" or "prophylactically effective" dose. Such effective doses will depend on a number of factors including the disease and the general health of the patient. Thus, dosing regimens can be determined and adjusted by qualified medical personnel to provide optimal therapeutic or prophylactic effect.

In the present method, one or more immunogenic polypeptides are typically administered at a dosage of about 1, 2, 5, 10, 20, 50, 100, 200, 500, or 1000 micrograms per immunogenic polypeptide or nucleic acid molecule or more, at least once. Preferably the dose is repeated one, two, three or more times at intervals of 2, 3 or 4 weeks.

According to one preferred embodiment, typical dosing regimens include administering a dose of 1-1000 μg per peptide per immunization, more preferably 10-500 μg per peptide per immunization, even more preferably 5-150 μg per peptide per immunization, at least once . Preferably the dose is repeated one, two, three or more times at intervals of 2, 3 or 4 weeks. In a preferred embodiment, 5-150 μg per peptide per immunization is administered, and repeated over a period of 2-3 weeks, one to several times per treatment.

The present method preferably comprises administering the present immunogenic polypeptides and compositions comprising them by the parenteral or oral route, preferably by the parenteral route. Preferred routes of administration include, but are not limited to, intratumoral, intramuscular, intranasal, intraperitoneal, intradermal, subcutaneous, intravenous, intraarterial, intraocular, and oral administration, as well as topical, transdermal, inhalation or suppository, or mucosal, e.g. lavage into rectal, urethral, buccal and sublingual tissues. Preferred routes of administration include intramuscular, intraperitoneal, intradermal and subcutaneous injection. In another embodiment, the introduction is made in the anatomical site, which flows into the lymphatic collector. In another embodiment, the introduction is made in several lymphatic collectors.

Particularly preferred is a combination of intradermal and subcutaneous administration of the drug according to the invention. DC in the epidermis clearly differs from DC in the dermis and subcutaneous tissue. Intradermal (intradermal) immunization will cause antigen processing and activation of epidermal DCs (langerin-positive Langerhans cells), which through their dendritic network are in close contact with keratinocytes. It also optimally activates inflammatory pathways in interactions between Langerhans cell and keratinocytes, followed by movement of the antigen-loaded and activated Langerhans cell to skin-draining lymph nodes. Subcutaneous injection activates other DC subsets, which will also be loaded with antigen and travel independently of the skin-draining lymph nodes. It is likely that the use of drugs that can be administered both intradermally and subcutaneously may lead to synergistic stimulation of T cells in these draining nodes by various DC subgroups.

The drug of the invention has the further advantage that when small amounts of drug, preferably a peptide, as defined earlier herein, are intradermally administered, an immunogenic effect can still be achieved. The amount of each peptide used is in the range of 0.3 to 1000 µg, more preferably 1 to 500 µg, even more preferably 5 to 150 µg. Another aspect of the invention relates to a pharmaceutical preparation containing as an active ingredient this source of the polypeptide, as defined herein previously. More specifically, the pharmaceutical preparation contains as an active ingredient one or more of the above immunogenic polypeptides selected from the group of ZP proteins, their homologues and fragments of said ZP proteins and their homologues, or alternatively, a gene therapy vector, as defined herein above.

According to a first embodiment, a pharmaceutical formulation is provided that contains one or more immunogenic polypeptides of the invention. The concentration of said polypeptide in a pharmaceutical composition can vary widely, i. from less than about 0.1% by weight, typically at least about 1% by weight, to as much as 20% by weight or more.

The composition preferably at least contains a pharmaceutically acceptable carrier in addition to the active ingredient. The pharmaceutical carrier may be any compatible, non-toxic substance suitable for delivery of immunogenic polypeptides or gene therapy vectors to a patient. For polypeptides, sterile water, alcohol, fats, waxes, and inert solids can be used as a carrier. Also included in the pharmaceutical compositions are pharmaceutically acceptable adjuvants, buffer agents, dispersants, and the like.

According to a particularly preferred embodiment, the present pharmaceutical composition contains an adjuvant as defined in more detail hereinbefore. Adjuvants for inclusion in the present composition are preferably selected from the group of ligands that are recognized by the toll-like receptor (TLR) present on antigen presenting cells and include lipopeptides (see e.g. WO 04/110486), lipopolysaccharides, peptidoglycans, lipoteichoic acids, lipoarabinomannans, lipoproteins (from mycoplasmas or spirochetes), double-stranded RNA (poly I:C), unmethylated DNA, flagellin, CpG-containing DNA, Pam3cysSK4, imidazoquinolines, and chemically modified derivatives of these ligands. The skilled artisan will be able to determine the exact amount of any of these adjuvants to be included in the present pharmaceutical preparations to render them sufficiently immunogenic. According to another preferred embodiment, the present pharmaceutical preparation may contain one or more additional ingredients that are used to enhance CTL immunity, as previously explained herein.

The composition of the medicinal products of the invention, for example, the composition containing the source of the immunogenic polypeptide, the routes of administration and the use of pharmaceutically acceptable excipients are known and accepted in the art and, for example, are described in "Remington: The Science and Practice of Pharmacy" (Ed. Allen, LV ^22nd edition, 2012, www.pharmpress.com).

Immunogenic polypeptides, nucleic acids encoding them or cells expressing them for use in the present invention can be obtained using recombinant methods such as those described in Ausubel et al., "Current Protocols in Molecular Biology", Greene Publishing and Wiley Interscience, New York (1987) and in Sambrook and Russell (2001) "Molecular Cloning: A Laboratory Manual" ( ^3rd edition), Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, New York; The contents of which are incorporated herein by reference in their entirety. See also, Kunkel (1985), Proc. Natl. Acad. sci. 82:488 (description of site-directed mutagenesis) and Roberts et al. (1987) Nature 328: 731 734 or Wells, JA, et al. (1985) Gene 34: 315 (describing cassette mutagenesis). More preferably, however, the immunogenic polypeptides of the invention, or the nucleic acids encoding them, are obtained by chemical synthesis. Chemical synthesis of peptides or nucleic acids is common practice and various suitable methods are known to the skilled person. The chemical synthesis of peptides or nucleic acids also solves the problems associated with recombinant production, which is more difficult to standardize and requires extensive purification and quality control measures.

In another aspect, the invention relates to a T cell containing a T cell receptor that binds an MHC-peptide complex, where the peptide is preferably a peptide containing or including epitopes restricted to MHC class I and MHC class II and contained in native ZP, preferably hZP3 or hZP3 (23-350), or a homologue of said one or more polypeptides. Such a T cell can be obtained, for example, by a method comprising contacting a T cell with an antigen presenting cell expressing a polynucleotide encoding an immunogenic polypeptide of the invention and/or contacting a T cell with an antigen presenting cell loaded with an immunogenic polypeptide of the invention; and optionally culturing said T cell. The antigen presenting cell (APC) is preferably a dendritic cell (DC). The T cell is preferably a CD8+ cytotoxic T cell or a CD4+ helper T cell. The introduction of a polynucleotide encoding an immunogenic polypeptide into APC or DC can be carried out by any method known to the person skilled in the art, preferably the polynucleotide of the invention is introduced into APC or DC using transfection. Preferably, the polynucleotide encoding the immunogenic polypeptide is provided with the appropriate control sequences or must be present in the appropriate expression vector. The contacting of T cells with an immunogenic polypeptide of the invention can be carried out by any method known to a person skilled in the art. Preferably, the immunogenic polypeptide or epitope contained in the immunogenic polypeptide is presented to a CD8+ cytotoxic T cell or CD4+ helper T cell with MHC class I or MHC class II molecules on the surface of the APC or DC. One skilled in the art knows how to load the APC or DC with the peptide. The cultivation of said T cell can be carried out by any method known to the person skilled in the art. Maintaining the T cells under the conditions necessary to keep the cells alive should also be considered herein as culture. Preferably, the T cell according to this aspect of the invention binds to the immunogenic polypeptide of the invention as defined in the first aspect of the invention. Methods for obtaining and activating T cells specific for tumor antigens ex vivo are described in more detail, for example, in WO2017/173321. In this aspect, the invention also relates to a composition comprising an (activated) T cell according to the invention, as well as methods according to the invention for the therapeutic and/or prophylactic treatment of lung cancer and/or metastases, comprising administering to an individual a therapeutic amount of (activated) tumor-specific T- cells described herein, or by the method described herein (see, for example, example 4). In embodiments, administration includes administration of about 10 ⁶ to 10 ¹² , about 10 ⁸ to 10 ¹¹ , or about 10 ⁹ to 10 ¹⁰ (activated) tumor-specific T cells. While the T-cell or composition is preferably administered via intravenous, intraperitoneal, intratumoral, intradermal or subcutaneous injection. In another embodiment, the T cell or composition is administered to an anatomic site that drains into a lymphatic collector. In another embodiment, the introduction is made in several lymphatic collectors.

A further aspect of the invention relates to a method for treating or diagnosing lung cancer and its metastases in an individual by administering an antibody or fragment thereof that specifically binds to an epitope of the human zona pellucida protein (hZP), preferably the antibody or fragment thereof specifically binds to an epitope of hZP3 or hZP3 (23 -350).

An antibody "that binds" an antigen of interest, e.g., a tumor-associated hZP protein antigen or an epitope thereof, is an antibody that binds the antigen with sufficient affinity such that the antibody is useful as a therapeutic agent when targeted to a cell or tissue expressing the antigen, and does not significantly cross-react with other proteins. In such embodiments, the degree of binding of an antibody to a "non-target" protein will be less than about 10% of the antibody's binding to its specific target protein, as determined by a fluorescence-activated cell sorting (FACS) or radioimmunoassay (RIA) assay. With regard to the binding of an antibody to a target molecule, the term "specific binding" or "specifically binds to" or "is specific for" a particular polypeptide or epitope on a particular polypeptide means a binding that is markedly different from a non-specific interaction. Specific binding can be measured, for example, by determining the binding of the molecule compared to the binding of a control molecule, which is typically the desired substance of similar structure without binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target, such as an excess of unlabeled target. In this case, specific binding is determined if binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. As used herein, the term "specific binding" or "specifically binds to" or "specific" for a particular polypeptide or epitope on a particular polypeptide target can be demonstrated, for example, by a molecule having a Kd for the target (which can be defined as described below) , at least about 10 ^-4 M, alternatively at least about 10 ^-5 M, alternatively at least about 10 ^-6 M, alternatively at least about 10 ^-7 M, alternatively, according to at least about 10 ^-8 M, alternatively at least about 10 ^-9 M, alternatively at least about 10 ^-10 M, alternatively at least about 10 ^-11 M, alternatively at least , approximately 10 ^-12 M, or more. In one embodiment, the term "specific binding" refers to binding in which a molecule binds to a specific polypeptide or epitope on a specific polypeptide substantially without binding to any other polypeptide or polypeptide epitope.

"Kd" or "Kd value" can be measured using surface plasmon resonance assays using a BIAcore™-2000 or BIAcore™-3000 (BIAcore, Inc., Piscataway, NJ) at 25°C with antigen immobilized CM5 chips at ~10 -50 response units (RE). Briefly, carboxymethylated dextran biosensor chips (CM5, BIAcore Inc.) are activated with N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) according to the supplier's instructions. The antigen is diluted with 10 mM sodium acetate, pH 4.8, to 5 μg/ml (± 0.2 μM) prior to injection at a flow rate of 5 μl/minute to achieve approximately 10 response units (RE) of bound protein. After injection of the antigen, 1 M ethanolamine is injected to block unreacted groups. To measure the kinetics, two-fold serial dilutions of the antibody or Fab (from 0.78 to 500 nM) are injected into PBS with 0.05% Tween 20 (PBST) at 25° C. at a flow rate of approximately 25 μl/min. Association rates (k _on ) and dissociation rates (k _off ) are calculated using a simple unambiguous Langmuir binding model (BIAcore Evaluation Software, version 3.2) by simultaneously fitting the association and dissociation sensorgram. The equilibrium dissociation constant (Kd) is calculated as the ratio k _off /k _on . See, for example, Chen, Y. et al., (1999) J. Mol. Biol. 293:865-881. If the forward reaction rate exceeds 10 ⁶ M ^-1 s ^-1 by surface plasmon resonance analysis is higher, then the forward reaction rate can be determined using a fluorescence quenching method that measures the increase or decrease in fluorescence intensity (excitation = 295 nm; emission = 340 nm, bandwidth 16 nm) at 25° C. with 20 nM anti-antigen antibody (Fab form) in PBS, pH 7.2, in the presence of increasing concentrations of antigen measured in a spectrometer such as a stop-flow spectrophotometer (Aviv Instruments) or a spectrophotometer SLM-Aminco 8000 series (ThermoSpectronic) with red stirred cell. The "forward reaction rate" or "association rate" or "k _on " of the present invention can also be determined using the same Surface Plasmon Resonance technique described above using a BIAcore™-2000 or BIAcore™-3000 (BIAcore , Inc., Piscataway, NJ) as described above.

As used herein, the term "antibody" is considered in a broad sense and refers to any type of immunoglobulin molecule, including polyclonal antibodies, monoclonal antibodies, including mice, human, human-adapted, humanized and chimeric monoclonal antibodies, antibody fragments, bispecific or polyspecific antibodies, dimeric, tetrameric or multimeric antibodies and single chain antibodies.

One embodiment of the invention relates to a method for treating lung cancer and its metastases in an individual, comprising administering to said individual a composition comprising an anti-ZP antibody, an anti-hZP3 antibody, or an anti-hZP3 antibody (23-350), wherein the antibody causes death of lung cancer cells by an antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-mediated cytotoxicity (CDC), or apoptosis. As generally understood by those skilled in the art, these antibody effector functions can be mediated by the Fc portion of the antibody, for example, by binding the Fc effector domain(s) to an Fc receptor on an immune cell with phagocytic or lytic activity, or by binding an effector Fc domain(s) with components of the complement system. Typically, the effect(s) mediated by Fc-binding cells or complement components will eventually lead to inhibition and/or depletion of the target cells, ie. ZP-expressing cells. Human IgG isotypes - IgG1, IgG2, IgG3 and IgG4 show differential ability to effector functions. ADCC can be mediated by IgG1 and IgG3, ADCP can be mediated by IgG1, IgG2, IgG3 and IgG4, and CDC can be mediated by IgG1 and IgG3. In the methods described herein, the hZP3 antibody or hZP3 antibody (23-350) is preferably an IgG1, IgG2, IgG3 or IgG4 antibody.

In the methods described herein, an anti-hZP3 antibody or an anti-hZP3 antibody (23-350) induces in vitro and/or in vivo death of lung cancer cells that express the ZP3 protein via antibody-dependent cellular cytotoxicity (ADCC). In the methods described herein, an anti-hZP3 antibody or an anti-hZP3 antibody (23-350) induces in vitro and/or in vitro death of lung cancer cells that express the ZP protein by complement dependent cytotoxicity (CDC). In the methods described herein, an anti-hZP3 antibody or an anti-hZP3 antibody (23-350) induces in vitro and/or in vitro death of lung cancer cells that express the ZP3 protein by antibody-dependent cellular phagocytosis (ADCP).

In the methods described herein, an anti-hZP3 antibody or an anti-hZP3 antibody (23-350) induces in vitro and/or in vitro death of lung cancer cells that express the ZP3 protein by apoptosis.

In the methods described herein, an anti-ZP antibody can bind human ZP with a range of affinities (K _D ). In one embodiment, an anti-ZP antibody binds ZP with high affinity, e.g., a K _D equal to or less than about 10 ^-7 M, such as, but not limited to, 1-9.9 (or any range or value within it, such as 1, 2, 3, 4, 5, 6, 7, 8, or 9)×10 ⁻⁸ , 10 ⁻⁹ , 10 ⁻¹⁰ , 10 ⁻¹¹ , 10 ⁻¹² , 10 ⁻¹³ , 10 ⁻¹⁴ , 10 ⁻¹⁵ or any range or value therein as determined by surface plasmon resonance or Kinexa (kinetic exclusion analysis) as practiced by those skilled in the art. In one example, the affinity is equal to or less than 1× ¹⁰⁻⁹ M. In another of the examples, the affinity is equal to or less than 1× ¹⁰⁻⁹ M.

Preferred antibodies for use in the present invention are monoclonal antibodies. Suitable (monoclonal) antibodies can be obtained, tested and produced by methods that are well known in the art and, for example, described in textbooks such as "Antibodies: A Laboratory Manual, Second edition, Edited by E.A. Greenfield, 2014, Cold Spring Harbor Laboratory Press. More specifically, Ranking et al. (1998, Development 125, 2415-2424) describe the generation of a monoclonal antibody H3.1 against the C-terminal peptide of the extracellular domain of hZP3 containing amino acids 335-350 of SEQ ID NO: 3. More preferably, antibodies for use in the present invention are humanized, or even more preferably human monoclonal antibodies, which can be obtained using methods well known in this field, such as, for example, described, respectively, in Olimpieri et al. (Bioinformatics. 2015; 31 (3): 434–435) and Sheehan and Marasco (Microbiol Spectr. 2015; 3 (1): AID-0028-2014) and in the references cited therein.

Any antibody that binds to the extracellular domain of the ZP protein, such as the extracellular domain of hZP3, ie. hZP3 (23-350), whose extracellular protein has the amino acid sequence of SEQ ID NO: 5, can be used for the present invention. Examples of suitable antibodies that can be used for the present invention include, for example, antibodies that are capable of cross-blocking the binding of one or more reference antibodies known to bind to hZP3 (23-350). One such reference antibody known to bind specifically to hZP3(23-350) is the H3.1 antibody described by Ranking et al. (1998, supra), for which the hybridoma is available from ATCC under accession number: ATCC CRL-2569.

Thus, a preferred antibody for use in the present invention has the ability to cross-block the binding of at least one antibody known to specifically bind to ZP, preferably hZP3, more preferably hZP3 (23-350) or a homologue of said polypeptide . More preferably, the antibody has the ability to cross-block binding of the H3.1 antibody with accession number ATCC CRL-2569. The ability of an anti-ZP antibody to cross-block the binding of a reference antibody is defined herein as the ability to reduce the binding of a reference antibody to an appropriate target molecule comprising the amino acid sequences ZP, hZP3, or hZP3 (23-350) by at least 10, 20, 50, 75%, 90%, 95%, 99%, 99.9% or 99.99% when the target molecule first binds to the anti-ZP antibody, or vice versa (i.e. the binding of the anti-ZP antibody decreases when the target molecule first binds to the reference antibody ). Cross-blocking capability can in principle be determined using any type of immunoassay, preferably a competitive immunoassay, including, for example, ELISA, direct or indirect radioimmunoassay (RIA), direct or indirect enzyme-linked immunoassay (EIA), competitive sandwich analysis (see Stahli et al., Methods in Enzymology 9:242-253 (1983)); solid phase direct biotin-avidin EIA (see Kirkland et al 20, J. Immunol. 137: 3614-3619 (1986)); labeled direct solid phase assay, labeled direct sandwich assay (see "Antibodies, A Laboratory Manual," Second edition, 2014; supra ); labeled solid phase direct RIA using I ¹²⁵ (see Morel et al., Molec. Immunol. 25 (1): 7-15 (1988)); solid phase direct biotin-avidin EIA (Cheung et al., Virology 176: 546-552 (1990)); and labeled direct RIA (Moldenhauer et al., Scand. J. Immunol. 32: 77-82 (1990)). Typically, such an assay involves the use of a purified target molecule bound to a solid surface, an unlabeled test antibody, and a labeled control antibody. Competitive inhibition is measured by determining the amount of label bound to a solid surface in the presence of the antigen-binding protein of interest. Typically, the antibody of interest is present in excess.

In the methods of the invention described herein, the anti-ZP antibody may be provided in suitable pharmaceutical compositions comprising the anti-ZP antibody and a pharmaceutically acceptable carrier. Suitable carriers and formulations including other human proteins, such as human serum albumin, are described, for example, in The Science and Practice of Pharmacy, 21st Edition, Troy, D. B. ed., Lipincott Williams and Wilkins, Philadelphia, Pa. 2006, Part 5, Pharmaceutical Manufacturing pp 691-1092, see especially pp. 958-989, see especially p. 958-989.

The route of administration of the anti-ZP antibody in the methods of the invention described herein may be any suitable route such as parenteral administration, e.g. intradermal, intramuscular, intraperitoneal, intravenous or subcutaneous, pulmonary, transmucosal (oral, intranasal, intravaginal or rectal) or other routes of administration understood by those skilled in the art as they are well known in the art. The anti-ZP antibody in the methods of the invention described herein may be administered to a patient by any suitable route, for example, by intravenous (IV) infusion or bolus injection, intramuscularly or subcutaneously, or intraperitoneally.

In the methods of the invention, the anti-ZP antibody is administered in a therapeutically effective amount. The term "therapeutically effective amount" refers to an amount effective in dosages and for periods of time necessary to achieve the desired therapeutic result. A therapeutically effective amount may vary depending on factors such as the disease state, age, sex, weight of the individual, and the ability of the therapeutic agent or combination of therapeutic agents to elicit the desired response in the individual. Exemplary indicators of an effective therapeutic agent or combination of therapeutic agents include, for example, improvement in the patient's well-being, reduction in tumor mass, arrest or slowing of tumor growth, and/or absence of metastasis of malignant cells to other places in the body.

The dose administered to an individual suffering from lung cancer is sufficient to alleviate or at least partially arrest the disease being treated ("therapeutic amount"), and sometimes can be from 0.005 mg to about 100 mg/kg, for example, from about 0.05 mg to about 30 mg/kg, or about 5 mg to about 25 mg/kg, or about 4 mg/kg, about 8 mg/kg, about 16 mg/kg, or about 24 mg/kg, or about 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 mg/kg, but may be even higher, such as about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 , 25, 30, 40, 50, 60, 70, 80, 90 or 100 mg/kg.

The present invention also relates to a method of treating lung cancer and its metastases in a subject using targeted therapy, typically by administering a composition comprising an antibody or fragment thereof capable of immunospecific binding to an epitope of the human zona pellucida protein (hZP), preferably the antibody or its the fragment is capable of immunospecific binding to an epitope of the human zona pellucida protein 3 (hZP3), wherein the antibody or fragment is part of an immunoconjugate, such as an immunotoxin, an antibody-drug conjugate, or a radioactive isotope-transferring antibody.

The term "immunoconjugate" refers to conjugates in which an antibody or fragment thereof is chemically linked to another molecule. When the molecule bound to an antibody or fragment thereof is a toxin, the immunoconjugate is known as an immunotoxin. When the molecule bound to an antibody or fragment thereof is a (cytotoxic) drug, the immunoconjugate is often referred to as "antibody-drug conjugate". The use of immunoconjugates for local delivery of cytotoxic or cytostatic agents, ie. drugs to kill or inhibit tumor cells in the treatment of cancer may allow targeted drug delivery to and intracellular accumulation in tumors, while systemic administration of these unconjugated drugs may result in unacceptable levels of toxicity to normal cells while tumor cells are avoided death. This achieves maximum efficiency with minimum toxicity. Efforts to develop and improve antibody conjugates have focused on the selectivity of monoclonal antibodies (mAbs) as well as drug binding and release properties.

In some embodiments, a radioactive isotope can be associated with an antibody, the resulting immunoconjugate is often referred to as an immunoradioactive isotope.

As will be understood by those skilled in the art, an anti-ZP moiety antibody can be an anti-ZP antibody having any or all of the characteristics previously described herein in relation to the passive immunization embodiment. The immunoconjugates may also comprise an antibody or fragment thereof that is simply capable of immunospecific binding to an epitope to an epitope of human zona pellucida protein (hZP), preferably an antibody or fragment thereof capable of immunospecific binding to an epitope to an epitope of human zona pellucida protein 3 (hZP3), without inducing any effector mechanisms.

The present invention further relates to immunoconjugates containing an antibody or fragment thereof conjugated to a radioactive isotope or radionuclide, or to a group (capable of containing) containing such a radionuclide. The experienced clinician will appreciate that there are many radionuclides that can be bound to tumor-specific antibodies by well-known methods and delivered to the target site for specific damage to tumor cells and tissues. For example, suitable reagents include ¹²⁵ I, ¹²³ I. ¹¹¹ In, ¹⁷⁷ Lu, ⁹⁰ Y, ²¹³ Bi, ²²⁵ Ac, and ^99m Tc. Among the radionuclides, yttrium-90 ( ⁹⁰ Y) may be particularly suitable for radioimmunotherapy, since yttrium-90 ( ⁹⁰ Y) provides advantages over iodine-131 ( ¹³¹ I), because it delivers higher beta energy (2.3 MeV compared to 0.61 MeV) against the tumor and has a path length of 5 to 10 mm, resulting in an improved ability to kill both target and neighboring cells, which is an advantage, in particular, with a bulky or poorly vascularized tumor.

In a further embodiment, the invention relates to a method for diagnosing and/or predicting lung cancer and/or its metastases and/or its recurrence in a human subject. The method is preferably used for the diagnosis and/or prognosis of non-small cell lung cancer and/or its metastases and/or its recurrence. The diagnostic and/or prognostic method preferably comprises administering an antibody or fragment thereof that specifically binds to an hZP epitope as well as hZP3 or hZP3 (23-350) as described above. The antibody or fragment thereof is preferably conjugated to an imaging agent or a detectable agent, preferably the agent is an in vivo imaging agent. Non-limiting examples of such agents include enzymes, radioactive labels, haptens, fluorescent labels, phosphorescent molecules, chemiluminescent molecules, chromophores, luminescent molecules, photoaffinity molecules, colored particles or ligands such as biotin, paramagnetic ions, radioactive isotopes, fluorochromes, NMR detectables. and x-ray imaging tools (see, for example, US20170240637 A1).

The phrase " in vivo imaging" as used herein refers to methods for detecting the presence of a detectable labeled antibody of the invention in a living mammal. Optically detectable proteins such as fluorescent antibodies and luciferase-associated antibodies can be detected using in vivo imaging. In vivo imaging can be used to obtain 2-D and 3-D images of a mammal. Radiolabeled antibodies, for example, can be administered to an individual and the individual is imaged using a gamma camera. For in vivo imaging, CCD cameras, CMOS, or 3D tomographs can be used. In vivo imaging techniques using computed tomography, magnetic resonance imaging, ultrasonography, positron emission tomography, single photon emission computed tomography (SPECT), and the like. well known in the art. Information from many in vivo imaging techniques, as described above, can provide data on cancer cells in an individual.

In diagnostic and/or prognostic methods, a detectable labeled antibody of the invention can be used to determine if an individual has lung cancer and/or its metastases and/or its recurrence, which is more or less amenable to the treatment described herein, and also to monitor the course of treatment and/or response to therapy in an individual. It can also be used to evaluate the course of other (combined) treatments. Thus, diagnostic/prognostic methods can inform the physician about the choice of therapy and treatment regimen.

In this document and in its claims, the verb "comprise" and its conjugations are used in a non-limiting sense to indicate that elements following the word are included, but elements not specifically mentioned are not excluded. Also, referring to an element with the indefinite article "a" or "an" does not rule out the possibility that more than one element is present, unless the context explicitly requires one and only one of the elements to be present. The indefinite article a" or "an" thus generally means "at least one".

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention in any way.

DESCRIPTION OF DRAWINGS

Figure 1 : ZP3 expression in lung cancer squamous cell carcinoma cells from three different patients. Each horizontal bar represents the results of one patient. From left to right, respectively, histopathology with hematoxylin-eosin (HEX5) staining; in situ hybridization of ZP3 mRNA expression (RNA volume X40); and immunohistochemistry of ZP3 protein expression (IHC X20). Overexpression of ZP3 is found exclusively in squamous cell carcinoma cells (SCC; arrows), and ZP3 expression is not seen in stromal cells (S) or healthy cells.

Figure 2 : ZP3 expression in lung cancer adenocarcinoma cells from three different patients. Each horizontal bar represents the results of one patient. From left to right, respectively, histopathology with hematoxylin-eosin (HEX5) staining; in situ hybridization of ZP3 mRNA expression (RNA volume X40); and immunohistochemistry of ZP3 protein expression (IHC X20). Overexpression of ZP3 is found exclusively in adenocarcinoma cells (ACC; arrows), and ZP3 expression is not seen in stromal cells (S) or healthy cells.

Figure 3 : Expression of ZP3 in the ovary (top row) and spleen (bottom row), as positive and negative controls, respectively. From left to right, respectively, histopathology with hematoxylin-eosin (HEX5) staining; in situ hybridization of ZP3 mRNA expression (RNA volume X40); and immunohistochemistry of ZP3 protein expression (IHC X20). The abundance of ZP3 mRNA was found in oocytes, and the ZP3 protein was found in ZP surrounding human oocytes, as well as in the cytoplasm of oocytes. In the spleen, ZP3 mRNA expression or protein was not detected.

Figure 4 : Selected hZP3 peptide sequences. Boxes and ovals contain the predicted class I and II MHC binders as indicated in Tables 2 and 5 and 3, respectively. Asterisks indicate potential N-linked glycosylation sites, and regions with a cluster of O-linked glycans are indicated in parentheses above the sequences.

Figure 5 : Schedule of administration of hZP3 positive B16-HLA-A2 melanoma tumor cells and hZP3 peptide mixture (comprising peptides 4, 5, 6, 8 and 9 in Table 5) or rhZP31-383 protein to HLA-A2 transgenic mice. On Day 0 (D0) was made subcutaneous (sc) injection of tumor 10 ⁶ cells/mouse. This was followed by a first injection from day 7 to day 10 (D7-10) and a booster injection on day 14 to day 17 (D14-17). Tumor size was monitored after treatment. From 30 to 35 mice per day were sacrificed to determine hZP3-specific CD8+ responses (ELISpot).

Figure 6 : Tumor size (in mm3) as a function of day after tumor challenge in PBS-treated control mice and mice after 2 subcutaneous immunizations with either rhZP31-383 protein or a combination of 5 hZP3 peptides (including peptides 4, 5, 6, 8 and 9 in Table 5).

figure 7 : CD8+ T cell responses as determined by interferon-γ (IFNg) ELISpot measured against peptides (all 5 or 4, 5, 6, 8 or 9 peptides individually) after immunization with hZP3 5 peptide mixture (peptide) or after immunization with ZP3 protein rhZP31-383 (protein).

EXAMPLES

Example 1

ZP3 expression in human lung cancer tissue was determined by immunohistochemistry (IHC). Tumor microarrays (TMA) from lung cancer tissues originating from different patients were obtained from the Institute of Pathology in the Netherlands.

Immunohistochemical determinations were performed with anti-ZP3 human monoclonal antibody H3.1 at two different concentrations, 1.0 μg ml and 0.1 μg/ml.

Human ovary sections containing oocytes were used as tissue positive controls. In addition, a spleen tissue sample was used as a negative control.

The following IHC protocol was used for all samples:

Day 1

1. Dewaxing and hydration:

a) Xylene - 3X3 min,

b) Absolute EtOH - 2X3 min

c) 96% EtOH - 2X3 min

d) 70% EtOH - 2X3 min

f) dH _20–1 – 1X10 min

2. Antigen extraction:

a) Buffer with 10 mM citric acid with 0.05% Tween 20 (pH 6.0) in extractor for 2.5 hours

b) chill

2. Wash sections in Tris buffered saline (TBS) with 0.05% Tween 20 (TBST) 3 times for 5 minutes each.

3. Incubate sections in 3% H ₂ O ₂ (diluted in TBS) for 15 minutes to quench endogenous peroxidase activity at room temperature (RT), in the dark.

4. Wash sections in TBST (TBS with 0.05% Tween 20) 2 times for 5 minutes each.

5. Incubate sections in 1 mg/ml sodium borohydride solution (diluted in TBS) for 15 minutes to quench free aldehyde groups (RT, in the dark, more important for IF staining, ZP3 co-localization).

6. Wash sections in TBST (TBS with 0.05% Tween 20) 3 times for 5 minutes each.

7. Incubate sections in blocking solution - 3% BSA in TBST (1 hour; RT; humidified chamber).

8. Incubate sections with primary anti-hZP3 antibody (1.0, 0.125, or 0.1 µg/mL) diluted in blocking solution (3% BSA in TBST) overnight in a humidified chamber in a cold room.

Day 2

1. Wash sections in TBST 3 times for 5 minutes each.

2. Incubate sections with DAKO anti-mouse polymer for 30 minutes (EnVision #4001).

3. Wash sections in TBST 3 times for 5 minutes each.

4. Incubate sections with chromogen system (DAKO, 1 drop per 1 ml buffer # K3468) - 10 min, stop the reaction by dipping the slides in a container of tap water.

5. Incubate sections in tap water for 2 minutes.

6. Rinse slides with ddH ₂ O before counterstaining

7. Contrast staining of sections in hematoxylin - 20-30 seconds.

8. Incubate sections in tap water to remove excess hematoxylin.

9. Dehydration of sections:

a) 70% EtOH - 2X3 min

b) 96% EtOH - 2X3 min

c) Absolute EtOH - 2X3 min

d) Xylene - 2X3 min

10. Fastening with Pertex.

In positive controls, antibodies detect proteins in the ZP surrounding the human oocyte. ZP3 proteins are also present in the oocyte cytoplasm. No positive staining was found in sections of lung cancer tissue specimens if the primary antibody is absent. No positive staining was observed with anti-ZP monoclonal antibody in spleen and liver tissue.

In lung cancer specimens (TMA), the presence of ZP3 is confirmed by areas of positive tissue staining for ZP3, with intensities varying among specimens obtained from different patients (see TMA results for squamous cell malignancies in Table 1). Such tumors stained positively for ZP3 expression can be treated by immunization with ZP3 antigens in accordance with the present invention.

Table 1. Non-small cell lung cancer (NSCLC) - Squamous cell malignant tumor, n=42 (TMA) Grade Result Percent Result Percent ZP3 antibody concentration
(1.0 µg/ml) ZP3 antibody concentration
(0.1 µg/ml) negative 1 2% 4 33% No rating 4 10% 6 14% Positive 37 88% 22 52% Details of a positive evaluation Weak (>0-1) 2 5% 2 9% Intermediate (>1-2) 24 65% 16 73% Strong (>2-3) eleven thirty% 4 18%

Example 2

ZP3 expression in human lung cancer tissues was determined by IHC (squamous cell malignancy, n=10 and lung adenocarcinoma, n=10) and volume RNA hybridization in situ (squamous cell malignancy, n=4 and lung adenocarcinoma, n=4). Tissue samples from different patients were obtained from the Institute of Pathology in Poland.

Immunohistochemical determinations were performed with human monoclonal antibodies to ZP3 at two different concentrations. The same IHC protocol as described in Example 1 was followed.

Human ovary sections were used as a tissue positive control. In addition, a sample of spleen tissue was used as a negative control.

In situ hybridization of formalin-embedded paraffin-embedded (FFPE) ovary samples was performed using Brown's RNAscope FFPE 2.0 HD Detection Kit [Advanced Cell Diagnostics (ACD), Hayward, California, USA, cat. No. 310033] according to the manufacturer's protocol.

Deparaffinization of FFPE sections

1. In a fume hood, fill two detergent bottles with ~200 ml fresh xylene and two with 200 ml fresh 100% ethanol.

2. Place the slides in the first xylene cleanser bottle and incubate for 5 minutes at room temperature. Stir the glasses by periodically moving the glass rack up and down in the detergent container.

3. Remove the slide rack from the first xylene cleanser bottle and immediately place into the second xylene cleanser bottle in a fume hood and repeat the incubation.

4. Remove the slide rack from the second xylene detergent bottle and immediately place it in a stain bottle containing 100% ethanol. Incubate the slides in 100% ethanol for 1 minute at room temperature with agitation.

5. Repeat step 4 with fresh 100% ethanol.

6. Remove the slides from the stand and place them cut side up on absorbent paper. Air dry for 5 minutes at room temperature.

Balance Equipment

1. Turn on the HybEZ™ oven and set the temperature to 40°C.

2. Place dampening paper in the moisture control tray and dampen completely with distilled water.

3. Insert the closed tray into the oven and close the oven door. Warm the tray for 30 minutes at 40°C before use.

Prepare 1X Pretreatment 2

Prepare 700 ml of fresh 1X Pretreatment 2 by adding 630 ml of distilled water to 1 vial (70 ml) of 10X Pretreatment 2 Solution in a 1 L beaker. Mix well. Place the glass containing 1X Pretreatment 2 on the hot stove. Cover the glass with foil and turn the hot stove on high for 10-15 minutes. Once 1X Pretreat 2 reaches a boil, turn the hotplate knob to 100-104°C to maintain an even boil.

Pretreatment 1 and 2

1. Apply a pre-treatment to cover the entire section and incubate for 10 minutes at room temperature.

2. Remove Pretreatment Solution 1 from one slide at a time by pressing the slide against absorbent paper and/or flicking. Immediately insert the slide into a slide holder immersed in a staining container filled with distilled water.

3. Rinse the slides twice in distilled water.

4. Apply Pretreatment 2. Make sure the 1X Pretreatment 2 solution is at a low boil. Using a pair of tongs, very slowly immerse the rack containing the slides into the boiling 1X Pretreatment 2 solution. Cover the beaker with foil and boil the slides for 15 minutes. After the pretreatment time is over, use tongs to immediately transfer the hot glass tray from 1X pretreatment 2 to the staining container containing distilled water. Do not let the glasses cool down in pretreatment 2.

5. Rinse the slides twice in distilled water.

6. Rinse the slides in fresh 100% ethanol by moving the stand up and down 3-5 times. Air dry the glasses. Create a hydrophobic barrier using the hydrophobic barrier pen.

7. Place the dried slides on the slide rack and add pre-treatment 3 to completely cover each section. Remove the HybEZ™ Moisture Control Tray from the HybEZ™ oven and place the HybEZ™ Glass Rack in the tray. Close the lid and put the tray back into the oven.

8. Incubate slides at 40°C for 30 minutes.

9. Remove the HybEZ™ moisture control tray from the oven.

10. Wash the slides twice with distilled water.

11. Add an appropriate probe to completely cover each section.

Probe for human ZP3 (catalog number 442631), positive control probe for low abundance transcripts (Mm-Polr-2a, # 312471), and negative control probe (DapB, ACD-310043).

Place the HybEZ™ Glass Rack in the HybEZ™ Moisture Control Tray, close the lid and place in the oven for 2 hours at 40°C.

12. Remove the HybEZ™ Control Tray from the oven and remove the HybEZ™ Glass Support.

13. Wash slides in 1X wash buffer for 2 minutes at room temperature. Stir the glasses by moving the glass holder up and down in the container.

14. Repeat step 13 with fresh 1X wash buffer.

15. Incubate Amp 1 slides with each section completely covered for 30 minutes at 40°C.

16. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

17. Incubate Amp 2 slides with each section completely covered for 15 minutes at 40°C.

18. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

19. Incubate Amp 3 slides with each section completely covered for 30 minutes at 40°C.

20. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

21. Incubate slides with Amp 4 with each section completely covered for 15 minutes at 40°C.

22. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

23. Incubate slides with Amp 5 with each section completely covered for 30 minutes at room temperature.

24. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

25. Incubate slides with Amp 6 with each section completely covered for 15 minutes at room temperature.

26. Wash slides twice in 1X wash buffer for 2 minutes at room temperature with occasional agitation.

27. Mix equal volumes of Brown-A and Brown-B (DAB substrate) in an appropriately sized tube, dispensing the same number of drops (2 drops of each reagent, 4 total) for each solution. Pipette DAB onto each tissue section. Make sure the sections are covered and incubate for 10 minutes at room temperature.

28. Rinse the slides in distilled water by moving the slide holder up and down 3-5 times. Replace with fresh distilled water.

29. Counterstaining of slides in a staining solution of 50% hematoxylin for 2 minutes at room temperature.

30. Rinse the slides in distilled water by moving the slide holder up and down 3-5 times. Repeat with fresh distilled water until the slides are clear and the areas remain purple.

31. Replace the distilled water in the stain container with 0.02% ammonia water. Move the stand up and down 2-3 times. The slice should turn blue. Replace ammonia water with distilled water. Rinse the glasses 3-5 times.

32. Dehydrate slides (70% ethanol for 2 minutes, 100%-70% ethanol for 2 minutes, xylene for 5 minutes).

33. Fix samples with Pertex.

In positive controls, antibodies detect proteins in the ZP surrounding the human oocyte as well as in the cytoplasm of the oocyte (FIG. 3, top row IHC X20). No positive staining was found in lung cancer tissue sections if the primary antibody was absent (not shown). No positive staining was observed with anti-ZP monoclonal antibody in spleen tissue (FIG. 3, bottom row of IHC X20).

In lung cancer specimens, in the squamous cell malignant tumor (Figure 1) and adenocarcinoma (Figure 2) subtypes, the presence of ZP3 is confirmed by areas of positive tissue staining for ZP3, both in ICS and in RNA volume, with intensities varying among specimens obtained from different patients Tumors , such as these that stain positive for ZP3 expression, can be treated by immunization with ZP3 antigens in accordance with the present invention.

Example 3

The hZP3 sequence was analyzed for HLA class I-restricted cytotoxic T cell (CTL) epitopes and HLA class II-restricted accessory epitopes using algorithms that predict peptide binding to HLA class I and II.

Class I MHC binding predictions are available using the NetCTLpan server from the Center for Biological Sequence Analysis (CBS) of the Technical University of Denmark (http://www.cbs.dtu.dk/services/NetCTLpan/) (Xu et al., 2012, Clin Dev Immunol 12:831010).

Class II MHC binding predictions were made using the IEDB Analysis Resource Consensus Tool (http://tools.immuneepitope.org/main/html/tcell_tools.html) (Stranzl et al., 2010, Immunogenetics; 62: 357-368 Wang et al., 2008, PLoS Comput Biol 4 (4): e1000048). This tool uses a variety of MHC class II epitope prediction methods, including a consensus approach that combines NN alignment, SMM alignment, and combinatorial library methods. A low percentile rank equals good binding agents.

The proposed alleles belonged to HLA class I and II supertypes (Wang et al., 2010, BMC Bioinformatics. 11:568; Sidney et al., 2008, BMC Immunol.; 9:1. Doi: 10.1186/1471-2172- 9-1). MHC molecules are extremely polymorphic, but despite this polymorphism, HLA class I molecules can be grouped into groups designated as supertypes, representing sets of molecules that have highly overlapping peptide binding specificities (Wang et al., 2010 BMC Bioinformatics. 11 : 568). Similarly, seven different supertypes are defined for HLA class II (core DR, DR4, DRB3, core DQ, DQ7, core DP and DP2) (Greenbaum et al., 2011, Immunogenetics.; 63 (6): 325-35).

The hZP3 peptide sequence was presented without the signal peptide and the transmembrane domain, i.e. from amino acids 23 to 387. The results of the analysis are shown in Tables 2 and 5 (MHC class I ligands) and in Table 3 (MHC class II ligands).

The MHC class I and II ligands shown in Tables 2 and 3, respectively, guide the design of the immunogenic peptides of the invention, for example, a composition comprising one or more polypeptides, wherein said one or more polypeptides comprise one or more epitopes restricted by the MHC class I and selected from Table 2, and/or epitopes restricted by MHC class II and selected from Table 3.

A series of hZP3 peptides spanning the hZP3 sequences for clinical use are shown in Figure 4. Predicted MHC class I and II binding sequences from Tables 2 and 3, as well as possible glycosylation sites, were considered to determine peptides, each containing a number of predicted binding sequences for MHC class I and II with a low percentile rank to induce a good immune response. These hZP3 peptide fragments include hZP3 ^30-78 (SEQ ID NO: 66), hZP3 ^76-101 (SEQ ID NO: 67), hZP3 ^99-141 (SEQ ID NO: 68), hZP3 ^138-187 (SEQ ID NO: 69), hZP3 ^185-225 (SEQ ID NO: 70), hZP3 ^224-267 (SEQ ID NO: 71), hZP3 ^257-290 (SEQ ID NO: 72), hZP3 ^298-317 (SEQ ID NO: 73) , hZP3 ^331-357 (SEQ ID NO: 74) and hZP3 ^358-383 (SEQ ID NO: 75). Combinations of these peptide fragments to form a composition containing combinations of at least two peptide fragments are listed in Table 4.

Table 2: Predicted MHC class I ligands contained in the hZP3 protein.

a/c* Ligand sequence HLA allele (% rank) SEQID NO: 34-42 HPETSVQPV HLA-B*07:02 (0.80) 6 35-43 PETSVQPVL HLA-B*40:01 (0.80) 7 47-55 ***QEATLMVMV HLA-B*40:01 (0.80) 8 49-57 ATLMVMVSK HLA-A*03:01 (0.30) 9 65-73 LIRAADLTL HLA-B*07:02 (0.80) 10 86-94 TEDVVRFEV HLA-B*40:01 (0.40) eleven 104-112 QVTDDALVY HLA-A*01:01 (0.30); HLA-A*26:01(0.40) 12 109-117 ALVYSTFLL HLA-A*02:01 (0.80) 13 115-123 FLLHDPRPV HLA-A*02:01 (0.80) 14 121-129 ^RPVGNLSIV¶ HLA-B*07:02 (0.30) 15 142-150 ^YPRQGNVSS¶ HLA-B*07:02 (0.80) 16 149-157 SSQAILPTW HLA-B*58:01 (0.10) 17 152-160 AILPTWLPF HLA-B*15:01 (0.80) 18 157-165 WLPFRTVF HLA-A*24:02 (0.80); HLA-B*08:01; HLA-B*15:01 (0.80) 19 164-172 VFSEEKLTF HLA-A*24:02 (0.30) 20 166-174 SEEKLTFSL HLA-B*40:01 (0.15) 21 175-183 RLMEENWNA HLA-A*02:01 (0.20) 22 190-198 FHLGDAAHL HLA-B*39:01 (0.05) 23 202-210 ***IHTGSHVPL HLA-B*39:01 (0.10) 24 228-234 SPYHTIVDF HLA-B*07:02 (0.80) 25 243-251 GLTDASSAF HLA-B*15:01 (0.20) 26 244-252 LTDASSAFK HLA-A*03:01 (0.80) 27 253-261 VPRPGPDTL HLA-B*07:02 (0.15) 28 255-263 RPGPDTLQF HLA-B*07:02 (0.30) 29 262-270 QFTVDVFHF HLA-A*24:02 (0.80) thirty 263-271 FTVDVFHFA HLA-A*02:01 (0.80); HLA-A*26:01(0.80) 31 271-279 ^ANDSRRNMIY¶ HLA-A*01:01 (0.30) 32 277-285 MIYITCHLK HLA-A*03:01 (0.10) 33 278-286 IYITCHLKV HLA-A*24:02 (0.20) 34 302-310 FSKPSNSWF HLA-B*15:01 (0.80) 35 304-312 KPSNSWFPV HLA-B*07:02 (0.30) 36 334-342 RQPHVMSQW HLA-A*24:02 (0.80) 37 371-379 RGDHEVEQW HLA-B*58:01 (0.80) 38 ^* Position of amino acids in the complete hZP3 protein.
^¶ The ligand contains an N-linked glycosylation site (position 125, 147 and 272, respectively).

Table 3 : Predicted MHC class II ligands contained in the hZP3 protein

a/a* Main Sequence HLA allele (percentile rank) ^§ SEQID NO: 48-56 EATLMVMVS DQA1*01:02/DQB*06:02 (0.14) 39 51-59 LMVMVSKDL DRB5*01:01 (0.88); DRB1*15:01 (2.37) 40 52-60 MVMVSKDLF DRB1*03:01 (1.01) 41 65-73 ****LIRAADTLTL DRB1*08:02 (2.49) 42 81-89 LVMSDTEDV DRB1*01:02 (1.31) 43 82-90 VSMDTEDVV DRB1*03:01 (0.54) 44 89-97 VVRFEVGLH DRB1*11:02 (0.52) 45 104-112 QVTDDALVY DRB1*03:01 (1.91) 46 109-117 ALVYSTFLL DPA1*01:03/DPB1*02:01(0.01); DPA1*02:01/DPB1*01:01 (0.12) 47 110-118 LVYSTFLLH DPA1*01/DPB1*04:01 (0.01); DPA1*0301/DPB1*04:02 (0.04) 48 115-123 FLLDPHRPV DRB1*11:02 (0.39) 49 116-124 LLHDPRPVG DRB1*03:01 (0.17) 50 126-134 *LSIVRTNRA ^‡ DRB1*08:02 (1.55) 51 128-136 IVRTNRAE DRB1*03:01 (1.77) 52 159-167 PFRTTVFSE DPA1*01:03/DPB1*02:01(0.58); HLA-DPA1*02:01/DPB1*01:01 (0.69) 53 160-168 FRTTVFSEE DPA1*01/DPB1*04:01 (0.35) 54 171-179 **TFSLRLMEE DQA1*04:01/DQB1*04:02 (1.05) 55 190-198 FHLGDAAHL DRB1*09:01 (0.49) 56 210-218 LRLFVDHCV DQA1*01:01 (0.48) 57 212-220 LFVDHCVAT DRB1*03:01 (2.05) 58 262-270 QFTVDVFHF DRB3*01:01 (1.5) 59 270-278 ^FANSNRMI¶ DRB3*01:01(0.35);DRB3*02:02(1.37); DRB1*03:01 (1.77) 60 278-286 IYITCHLKV DRB1*11:01(1.16); DPA1*03:01/DPB1*04:02 (1.53) 61 339-347 VMSQWSRSA DRB1*11:02 (0.79) 62 343-351 WSRSASRNR DRB5*01:01 (1.4) 63 365-373 LIFLDRRGD DRB1*11:02 (1.01) 64 366-374 IFLDRRGDH DRB1*03:01 (0.08) 65 ^* Position of amino acids in the complete hZP3 protein.
^§ The percentile rank is given in brackets after the corresponding HLA allele; only ligands with percentile ranks > 2.5 are considered.
^‡ N-linked glycosylation site at preceding position 125.
^¶ The ligand contains an N-linked glycosylation site (position 272).

Example 4

With in silico prediction software, potential HLA-A2 restricted T-cell epitopes from the rhZP3 protein were identified. The software was NETMHCPAN 3.0 in silico prediction software.

Table 5 : T-cell epitopes from the rhZP3 protein restricted by HLA-A2.

Number Position Peptide Affinity (nM) % rank SEQID NO 1 115 FLLHDPRPV 5.1 0.04 76 2 175 RLMEENWNA 5.2 0.04 77 3 109 ALVYSTFLL 21.3 0.3 78 4 263 FTVDVFHFA 19.9 0.3 79 5 174 LRLMEENWNA 28.6 0.4 80 6 367 FLDRRGDHEV 53.2 0.7 81 7 239 CLVDGLTDA 79.1 0.9 82 8 276 NMIYITCHL 76.6 0.9 83 9 114 TFLLHDPRPV 101.9 1.1 84 10 64 KLIRAADLTL 129.9 1.2 85

A preclinical study was conducted on the effectiveness of in vivo assessment of the immune response and antitumor response after immunization with the rhZP3 polypeptide (1-383 with his-tag) and five different ZP3 epitopes. The hZP3 epitopes were selected based on CD8+ T cell responses observed in previous immunogenic experiments with the rhZP3 polypeptide (a/c 1-383) and a pool of peptides containing hZP3 epitopes as indicated (see Table 5), in combination with various adjuvants (data not shown). Peptides were synthesized in Pepscan (Netherlands) with >96% purity.

In this experiment, under therapeutic conditions, HLA-A2 transgenic mice with a tumor expressing ZP3 were treated with rhZP3 protein, hZP3 peptide array, or PBS as controls.

An HLA-A2 transgenic mouse model was used for this study. To create a tumor model, a B16-HLA-A2 transgenic mouse melanoma cell line was transfected with rhZP3 (see example in Tran et al., Clin. Cancer Res, 2016; 22 (16): 4133-44).

Three groups of female HLA-A2 transgenic mice (n=6) with tumors expressing ZP3 were treated with:

1. PBS;

2. Pool of five hZP3 peptides (5 dominant peptides previously identified in HLA-A2/DR1 mice, including epitopes identified as 4, 5, 6, 8, and 9 in Table 5; 0.5 nmol per peptide) plus GM-CSF /CpG as adjuvant (20 µg GM-CSF and 50 µg CpG); And,

3. rhZP3 protein (100 µg, s.c.) plus GM-CSF/CpG as an adjuvant (20 µg GM-CSF and 50 µg CpG).

On day 0 (D0), the tumor was injected with 10 ⁶ cells/mouse (subcutaneously). Thereafter, a priming injection was administered between days 7 to 10 (D7-10) and a stimulating injection on days 14 to 17 (D14-17). Tumor size was monitored after treatment. On the day from 30 to 35 mice were sacrificed to determine the ZP3-specific TCD8+ response (ELISpot). See graph in figure 5.

Tumor size increased after PBS administration, while no tumor growth was observed after two subcutaneous immunizations with either the rhZP3 protein or the hZP3 five peptide combination (see FIG. 6).

In addition, as shown in Figure 7, a strong CD8+ T cell response (IFNg) against the peptides was measured after immunization with five hZP3 peptides. Also, after immunization with ZP3 protein, a TCD8 response was observed (see Figure 7).

Table 4 Combinations of amino acid sequences from Figure 4 to be included in immunogenic peptides to formulate synthetic long peptides according to the invention. The various combinations are separated by semicolons.

Combination of 2 peptides

SEQID NO. 66, SEQ ID NO. 67; SEQID NO. 66, SEQ ID NO. 68; SEQID NO. 66, SEQ ID NO. 69; SEQID NO. 66, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68; SEQID NO. 67, SEQ ID NO. 69; SEQID NO. 67, SEQ ID NO. 70; SEQID NO. 67, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69; SEQID NO. 68, SEQ ID NO. 70; SEQID NO. 68, SEQ ID NO. 71; SEQID NO. 68, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70; SEQID NO. 69, SEQ ID NO. 71; SEQID NO. 69, SEQ ID NO. 72; SEQID NO. 69, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71; SEQID NO. 70, SEQ ID NO. 72; SEQID NO. 70, SEQ ID NO. 73; SEQID NO. 70, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 72; SEQID NO. 71, SEQ ID NO. 73; SEQID NO. 71, SEQ ID NO. 74; SEQID NO. 71, SEQ ID NO. 75; SEQID NO. 72, SEQ ID NO. 73; SEQID NO. 72, SEQ ID NO. 74; SEQID NO. 72, SEQ ID NO. 75; SEQID NO. 73, SEQ ID NO. 74; SEQID NO. 73, SEQ ID NO. 75; SEQID NO. 74, SEQ ID NO. 75;

Combination of 3 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75;

Combination of 4 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75;

Combination of 5 peptides

SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75;

Combination of 6 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO.75;

Combination of 7 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75;

Combination of 8 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75;

Combination of 9 peptides

SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 68, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 67, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 66, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75; SEQID NO. 67, SEQ ID NO. 68, SEQ ID NO. 69, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, SEQ ID NO. 73, SEQ ID NO. 74, SEQ ID NO. 75.

Table 6 Combinations of amino acid sequences from Table 5 to be included in immunogenic peptides to formulate synthetic long peptides according to the invention. The various combinations are separated by semicolons.

Combination of 2 peptides

SEQID NO. 76, SEQ ID NO. 77; SEQID NO. 76, SEQ ID NO. 78; SEQID NO. 76, SEQ ID NO. 79; SEQID NO. 76, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78; SEQID NO. 77, SEQ ID NO. 79; SEQID NO. 77, SEQ ID NO. 80; SEQID NO. 77, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79; SEQID NO. 78, SEQ ID NO. 80; SEQID NO. 78, SEQ ID NO. 81; SEQID NO. 78, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80; SEQID NO. 79, SEQ ID NO. 81; SEQID NO. 79, SEQ ID NO. 82; SEQID NO. 79, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81; SEQID NO. 80, SEQ ID NO. 82; SEQID NO. 80, SEQ ID NO. 83; SEQID NO. 80, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 82; SEQID NO. 81, SEQ ID NO. 83; SEQID NO. 81, SEQ ID NO. 84; SEQID NO. 81, SEQ ID NO. 85; SEQID NO. 82, SEQ ID NO. 83; SEQID NO. 82, SEQ ID NO. 84; SEQID NO. 82, SEQ ID NO. 85; SEQID NO. 83, SEQ ID NO. 84; SEQID NO. 83, SEQ ID NO. 85; SEQID NO. 84, SEQ ID NO. 85;

Combination of 3 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 4 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 5 peptides

SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 6 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 7 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 8 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85;

Combination of 9 peptides

SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 78, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 77, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 76, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85; SEQID NO. 77, SEQ ID NO. 78, SEQ ID NO. 79, SEQ ID NO. 80, SEQ ID NO. 81, SEQ ID NO. 82, SEQ ID NO. 83, SEQ ID NO. 84, SEQ ID NO. 85.

--->

SEQUENCE LIST

<110> Pantarhei Bioscience B.V.

<120> Immunotherapeutic methods for the treatment and/or prevention of lung cancer

<130> P6066722PCT

<150>EP17199441.1

<151> 2017-10-31

<160> 85

<170>PatentIn version 3.5

<210> 1

<211> 638

<212> Protein

<213> Homo sapiens

<400> 1

Met Ala Gly Gly Ser Ala Thr Thr Trp Gly Tyr Pro Val Ala Leu Leu

1 5 10 15

Leu Leu Val Ala Thr Leu Gly Leu Gly Arg Trp Leu Gln Pro Asp Pro

20 25 30

Gly Leu Pro Gly Leu Arg His Ser Tyr Asp Cys Gly Ile Lys Gly Met

35 40 45

Gln Leu Leu Val Phe Pro Arg Pro Gly Gln Thr Leu Arg Phe Lys Val

50 55 60

Val Asp Glu Phe Gly Asn Arg Phe Asp Val Asn Asn Cys Ser Ile Cys

65 70 75 80

Tyr His Trp Val Thr Ser Arg Pro Gln Glu Pro Ala Val Phe Ser Ala

85 90 95

Asp Tyr Arg Gly Cys His Val Leu Glu Lys Asp Gly Arg Phe His Leu

100 105 110

Arg Val Phe Met Glu Ala Val Leu Pro Asn Gly Arg Val Asp Val Ala

115 120 125

Gln Asp Ala Thr Leu Ile Cys Pro Lys Pro Asp Pro Ser Arg Thr Leu

130 135 140

Asp Ser Gln Leu Ala Pro Pro Ala Met Phe Ser Val Ser Thr Pro Gln

145 150 155 160

Thr Leu Ser Phe Leu Pro Thr Ser Gly His Thr Ser Gln Gly Ser Gly

165 170 175

His Ala Phe Pro Ser Pro Leu Asp Pro Gly His Ser Ser Val His Pro

180 185 190

Thr Pro Ala Leu Pro Ser Pro Gly Pro Gly Pro Thr Leu Ala Thr Leu

195 200 205

Ala Gln Pro His Trp Gly Thr Leu Glu His Trp Asp Val Asn Lys Arg

210 215 220

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

225 230 235 240

Gly His Leu Pro Cys Ile Val Arg Arg Thr Ser Lys Glu Ala Cys Gln

245 250 255

Gln Ala Gly Cys Cys Tyr Asp Asn Thr Arg Glu Val Pro Cys Tyr Tyr

260 265 270

Gly Asn Thr Ala Thr Val Gln Cys Phe Arg Asp Gly Tyr Phe Val Leu

275 280 285

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

290 295 300

Ile His Leu Ala Tyr Ala Pro Thr Ser Cys Ser Pro Thr Gln His Thr

305 310 315 320

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

325 330 335

Met Gln Val Ala Gly Asp Gln Leu Ile Tyr Glu Asn Trp Leu Val Ser

340 345 350

Gly Ile His Ile Gln Lys Gly Pro Gln Gly Ser Ile Thr Arg Asp Ser

355 360 365

Thr Phe Gln Leu His Val Arg Cys Val Phe Asn Ala Ser Asp Phe Leu

370 375 380

Pro Ile Gln Ala Ser Ile Phe Pro Pro Ser Pro Ala Pro Met Thr

385 390 395 400

Gln Pro Gly Pro Leu Arg Leu Glu Leu Arg Ile Ala Lys Asp Glu Thr

405 410 415

Phe Ser Ser Tyr Tyr Gly Glu Asp Asp Tyr Pro Ile Val Arg Leu Leu

420 425 430

Arg Glu Pro Val His Val Glu Val Arg Leu Leu Gln Arg Thr Asp Pro

435 440 445

Asn Leu Val Leu Leu Leu His Gln Cys Trp Gly Ala Pro Ser Ala Asn

450 455 460

Pro Phe Gln Gln Pro Gln Trp Pro Ile Leu Ser Asp Gly Cys Pro Phe

465 470 475 480

Lys Gly Asp Ser Tyr Arg Thr Gln Met Val Ala Leu Asp Gly Ala Thr

485 490 495

Pro Phe Gln Ser His Tyr Gln Arg Phe Thr Val Ala Thr Phe Ala Leu

500 505 510

Leu Asp Ser Gly Ser Gln Arg Ala Leu Arg Gly Leu Val Tyr Leu Phe

515 520 525

Cys Ser Thr Ser Ala Cys His Thr Ser Gly Leu Glu Thr Cys Ser Thr

530 535 540

Ala Cys Ser Thr Gly Thr Thr Arg Gln Arg Arg Ser Ser Gly His Arg

545 550 555 560

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

565 570 575

Gly Phe Glu Asp Ser Tyr Gly Gln Glu Pro Thr Leu Gly Pro Thr Asp

580 585 590

Ser Asn Gly Asn Ser Ser Leu Arg Pro Leu Leu Trp Ala Val Leu Leu

595 600 605

Leu Pro Ala Val Ala Leu Val Leu Gly Phe Gly Val Phe Val Gly Leu

610 615 620

Ser Gln Thr Trp Ala Gln Lys Leu Trp Glu Ser Asn Arg Gln

625 630 635

<210> 2

<211> 745

<212> Protein

<213> Homo sapiens

<400> 2

Met Ala Cys Arg Gln Arg Gly Gly Ser Trp Ser Pro Ser Gly Trp Phe

1 5 10 15

Asn Ala Gly Trp Ser Thr Tyr Arg Ser Ile Ser Leu Phe Phe Ala Leu

20 25 30

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

35 40 45

Phe Pro Gly Thr Val Thr Cys Asp Glu Arg Glu Ile Thr Val Glu Phe

50 55 60

Pro Ser Ser Pro Gly Thr Lys Lys Trp His Ala Ser Val Val Asp Pro

65 70 75 80

Leu Gly Leu Asp Met Pro Asn Cys Thr Tyr Ile Leu Asp Pro Glu Lys

85 90 95

Leu Thr Leu Arg Ala Thr Tyr Asp Asn Cys Thr Arg Arg Val His Gly

100 105 110

Gly His Gln Met Thr Ile Arg Val Met Asn Asn Ser Ala Ala Leu Arg

115 120 125

His Gly Ala Val Met Tyr Gln Phe Phe Cys Pro Ala Met Gln Val Glu

130 135 140

Glu Thr Gln Gly Leu Ser Ala Ser Thr Ile Cys Gln Lys Asp Phe Met

145 150 155 160

Ser Phe Ser Leu Pro Arg Val Phe Ser Gly Leu Ala Asp Asp Ser Lys

165 170 175

Gly Thr Lys Val Gln Met Gly Trp Ser Ile Glu Val Gly Asp Gly Ala

180 185 190

Arg Ala Lys Thr Leu Thr Leu Pro Glu Ala Met Lys Glu Gly Phe Ser

195 200 205

Leu Leu Ile Asp Asn His Arg Met Thr Phe His Val Pro Phe Asn Ala

210 215 220

Thr Gly Val Thr His Tyr Val Gln Gly Asn Ser His Leu Tyr Met Val

225 230 235 240

Ser Leu Lys Leu Thr Phe Ile Ser Pro Gly Gln Lys Val Ile Phe Ser

245 250 255

Ser Gln Ala Ile Cys Ala Pro Asp Pro Val Thr Cys Asn Ala Thr His

260 265 270

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

275 280 285

Phe Glu Asn Gln Asn Ile Asp Val Ser Gln Leu His Asp Asn Gly Ile

290 295 300

Asp Leu Glu Ala Thr Asn Gly Met Lys Leu His Phe Ser Lys Thr Leu

305 310 315 320

Leu Lys Thr Lys Leu Ser Glu Lys Cys Leu Leu His Gln Phe Tyr Leu

325 330 335

Ala Ser Leu Lys Leu Thr Phe Leu Leu Arg Pro Glu Thr Val Ser Met

340 345 350

Val Ile Tyr Pro Glu Cys Leu Cys Glu Ser Pro Val Ser Ile Val Thr

355 360 365

Gly Glu Leu Cys Thr Gln Asp Gly Phe Met Asp Val Glu Val Tyr Ser

370 375 380

Tyr Gln Thr Gln Pro Ala Leu Asp Leu Gly Thr Leu Arg Val Gly Asn

385 390 395 400

Ser Ser Cys Gln Pro Val Phe Glu Ala Gln Ser Gln Gly Leu Val Arg

405 410 415

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

420 425 430

Asp Lys Val Val Tyr Glu Asn Glu Ile His Ala Leu Trp Thr Asp Phe

435 440 445

Pro Pro Ser Lys Ile Ser Arg Asp Ser Glu Phe Arg Met Thr Val Lys

450 455 460

Cys Ser Tyr Ser Arg Asn Asp Met Leu Leu Asn Ile Asn Val Glu Ser

465 470 475 480

Leu Thr Pro Pro Val Ala Ser Val Lys Leu Gly Pro Phe Thr Leu Ile

485 490 495

Leu Gln Ser Tyr Pro Asp Asn Ser Tyr Gln Gln Pro Tyr Gly Glu Asn

500 505 510

Glu Tyr Pro Leu Val Arg Phe Leu Arg Gln Pro Ile Tyr Met Glu Val

515 520 525

Arg Val Leu Asn Arg Asp Asp Pro Asn Ile Lys Leu Val Leu Asp Asp

530 535 540

Cys Trp Ala Thr Ser Thr Met Asp Pro Asp Ser Phe Pro Gln Trp Asn

545 550 555 560

Val Val Val Asp Gly Cys Ala Tyr Asp Leu Asp Asn Tyr Gln Thr Thr

565 570 575

Phe His Pro Val Gly Ser Ser Val Thr His Pro Asp His Tyr Gln Arg

580 585 590

Phe Asp Met Lys Ala Phe Ala Phe Val Ser Glu Ala His Val Leu Ser

595 600 605

Ser Leu Val Tyr Phe His Cys Ser Ala Leu Ile Cys Asn Arg Leu Ser

610 615 620

Pro Asp Ser Pro Leu Cys Ser Val Thr Cys Pro Val Ser Ser Arg His

625 630 635 640

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

645 650 655

Pro Gly Pro Ile Leu Leu Leu Ser Asp Asp Ser Ser Phe Arg Gly Val

660 665 670

Gly Ser Ser Asp Leu Lys Ala Ser Gly Ser Ser Gly Glu Lys Ser Arg

675 680 685

Ser Glu Thr Gly Glu Glu Val Gly Ser Arg Gly Ala Met Asp Thr Lys

690 695 700

Gly His Lys Thr Ala Gly Asp Val Gly Ser Lys Ala Val Ala Ala Val

705 710 715 720

Ala Ala Phe Ala Gly Val Val Ala Thr Leu Gly Phe Ile Tyr Tyr Leu

725 730 735

Tyr Glu Lys Arg Thr Val Ser Asn His

740 745

<210> 3

<211> 424

<212> Protein

<213> Homo sapiens

<400> 3

Met Glu Leu Ser Tyr Arg Leu Phe Ile Cys Leu Leu Leu Trp Gly Ser

1 5 10 15

Thr Glu Leu Cys Tyr Pro Gln Pro Leu Trp Leu Leu Gln Gly Gly Ala

20 25 30

Ser His Pro Glu Thr Ser Val Gln Pro Val Leu Val Glu Cys Gln Glu

35 40 45

Ala Thr Leu Met Val Met Val Ser Lys Asp Leu Phe Gly Thr Gly Lys

50 55 60

Leu Ile Arg Ala Ala Asp Leu Thr Leu Gly Pro Glu Ala Cys Glu Pro

65 70 75 80

Leu Val Ser Met Asp Thr Glu Asp Val Val Arg Phe Glu Val Gly Leu

85 90 95

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

100 105 110

Ser Thr Phe Leu Leu His Asp Pro Arg Pro Val Gly Asn Leu Ser Ile

115 120 125

Val Arg Thr Asn Arg Ala Glu Ile Pro Ile Glu Cys Arg Tyr Pro Arg

130 135 140

Gln Gly Asn Val Ser Ser Gln Ala Ile Leu Pro Thr Trp Leu Pro Phe

145 150 155 160

Arg Thr Thr Val Phe Ser Glu Glu Lys Leu Thr Phe Ser Leu Arg Leu

165 170 175

Met Glu Glu Asn Trp Asn Ala Glu Lys Arg Ser Pro Thr Phe His Leu

180 185 190

Gly Asp Ala Ala His Leu Gln Ala Glu Ile His Thr Gly Ser His Val

195 200 205

Pro Leu Arg Leu Phe Val Asp His Cys Val Ala Thr Pro Thr Pro Asp

210 215 220

Gln Asn Ala Ser Pro Tyr His Thr Ile Val Asp Phe His Gly Cys Leu

225 230 235 240

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

245 250 255

Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn

260 265 270

Asp Ser Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu

275 280 285

Ala Glu Gln Asp Pro Asp Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys

290 295 300

Pro Ser Asn Ser Trp Phe Pro Val Glu Gly Ser Ala Asp Ile Cys Gln

305 310 315 320

Cys Cys Asn Lys Gly Asp Cys Gly Thr Pro Ser His Ser Arg Arg Gln

325 330 335

Pro His Val Met Ser Gln Trp Ser Arg Ser Ala Ser Arg Asn Arg Arg

340 345 350

His Val Thr Glu Glu Ala Asp Val Thr Val Gly Pro Leu Ile Phe Leu

355 360 365

Asp Arg Arg Gly Asp His Glu Val Glu Gln Trp Ala Leu Pro Ser Asp

370 375 380

Thr Ser Val Val Leu Leu Gly Val Gly Leu Ala Val Val Val Ser Leu

385 390 395 400

Thr Leu Thr Ala Val Ile Leu Val Leu Thr Arg Arg Cys Arg Thr Ala

405 410 415

Ser His Pro Val Ser Ala Ser Glu

420

<210> 4

<211> 540

<212> Protein

<213> Homo sapiens

<400> 4

Met Trp Leu Leu Arg Cys Val Leu Leu Cys Val Ser Leu Ser Leu Ala

1 5 10 15

Val Ser Gly Gln His Lys Pro Glu Ala Pro Asp Tyr Ser Ser Val Leu

20 25 30

His Cys Gly Pro Trp Ser Phe Gln Phe Ala Val Asn Leu Asn Gln Glu

35 40 45

Ala Thr Ser Pro Pro Val Leu Ile Ala Trp Asp Asn Gln Gly Leu Leu

50 55 60

His Glu Leu Gln Asn Asp Ser Asp Cys Gly Thr Trp Ile Arg Lys Gly

65 70 75 80

Pro Gly Ser Ser Val Val Leu Glu Ala Thr Tyr Ser Ser Cys Tyr Val

85 90 95

Thr Glu Trp Asp Ser His Tyr Ile Met Pro Val Gly Val Glu Gly Ala

100 105 110

Gly Ala Ala Glu His Lys Val Val Thr Glu Arg Lys Leu Leu Lys Cys

115 120 125

Pro Met Asp Leu Leu Ala Arg Asp Ala Pro Asp Thr Asp Trp Cys Asp

130 135 140

Ser Ile Pro Ala Arg Asp Arg Leu Pro Cys Ala Pro Ser Pro Ile Ser

145 150 155 160

Arg Gly Asp Cys Glu Gly Leu Gly Cys Cys Tyr Ser Ser Glu Glu Val

165 170 175

Asn Ser Cys Tyr Tyr Gly Asn Thr Val Thr Leu His Cys Thr Arg Glu

180 185 190

Gly His Phe Ser Ile Ala Val Ser Arg Asn Val Thr Ser Pro Pro Leu

195 200 205

Leu Leu Asp Ser Val Arg Leu Ala Leu Arg Asn Asp Ser Ala Cys Asn

210 215 220

Pro Val Met Ala Thr Gln Ala Phe Val Leu Phe Gln Phe Pro Phe Thr

225 230 235 240

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

245 250 255

Asn Glu Leu Val Ala Thr Arg Asp Val Lys Asn Gly Ser Arg Gly Ser

260 265 270

Val Thr Arg Asp Ser Ile Phe Arg Leu His Val Ser Cys Ser Tyr Ser

275 280 285

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

290 295 300

Pro Pro Phe Pro Glu Thr Gln Pro Gly Pro Leu Thr Leu Glu Leu Gln

305 310 315 320

Ile Ala Lys Asp Lys Asn Tyr Gly Ser Tyr Tyr Gly Val Gly Asp Tyr

325 330 335

Pro Val Val Lys Leu Leu Arg Asp Pro Ile Tyr Val Glu Val Ser Ile

340 345 350

Leu His Arg Thr Asp Pro Tyr Leu Gly Leu Leu Leu Gln Gln Cys Trp

355 360 365

Ala Thr Pro Ser Thr Asp Pro Leu Ser Gln Pro Gln Trp Pro Ile Leu

370 375 380

Val Lys Gly Cys Pro Tyr Ile Gly Asp Asn Tyr Gln Thr Gln Leu Ile

385 390 395 400

Pro Val Gln Lys Ala Leu Asp Leu Pro Phe Pro Ser His His Gln Arg

405 410 415

Phe Ser Ile Phe Thr Phe Ser Phe Val Asn Pro Thr Val Glu Lys Gln

420 425 430

Ala Leu Arg Gly Pro Val His Leu His Cys Ser Val Ser Val Cys Gln

435 440 445

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

450 455 460

Arg Arg Asn Phe Asp Asn Ser Ser Gln Asn Thr Thr Ala Ser Val Ser

465 470 475 480

Ser Lys Gly Pro Met Ile Leu Leu Gln Ala Thr Lys Asp Pro Pro Glu

485 490 495

Lys Leu Arg Val Pro Val Asp Ser Lys Val Leu Trp Val Ala Gly Leu

500 505 510

Ser Gly Thr Leu Ile Leu Gly Ala Leu Leu Val Ser Tyr Leu Ala Val

515 520 525

Lys Lys Gln Lys Ser Cys Pro Asp Gln Met Cys Gln

530 535 540

<210> 5

<211> 328

<212> Protein

<213> Homo sapiens

<400> 5

Gln Pro Leu Trp Leu Leu Gln Gly Gly Ala Ser His Pro Glu Thr Ser

1 5 10 15

Val Gln Pro Val Leu Val Glu Cys Gln Glu Ala Thr Leu Met Val Met

20 25 30

Val Ser Lys Asp Leu Phe Gly Thr Gly Lys Leu Ile Arg Ala Ala Asp

35 40 45

Leu Thr Leu Gly Pro Glu Ala Cys Glu Pro Leu Val Ser Met Asp Thr

50 55 60

Glu Asp Val Val Arg Phe Glu Val Gly Leu His Glu Cys Gly Asn Ser

65 70 75 80

Met Gln Val Thr Asp Asp Ala Leu Val Tyr Ser Thr Phe Leu Leu His

85 90 95

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

100 105 110

Glu Ile Pro Ile Glu Cys Arg Tyr Pro Arg Gln Gly Asn Val Ser Ser

115 120 125

Gln Ala Ile Leu Pro Thr Trp Leu Pro Phe Arg Thr Thr Val Phe Ser

130 135 140

Glu Glu Lys Leu Thr Phe Ser Leu Arg Leu Met Glu Glu Asn Trp Asn

145 150 155 160

Ala Glu Lys Arg Ser Pro Thr Phe His Leu Gly Asp Ala Ala His Leu

165 170 175

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

180 185 190

Asp His Cys Val Ala Thr Pro Thr Pro Asp Gln Asn Ala Ser Pro Tyr

195 200 205

His Thr Ile Val Asp Phe His Gly Cys Leu Val Asp Gly Leu Thr Asp

210 215 220

Ala Ser Ser Ala Phe Lys Val Pro Arg Pro Gly Pro Asp Thr Leu Gln

225 230 235 240

Phe Thr Val Asp Val Phe His Phe Ala Asn Asp Ser Arg Asn Met Ile

245 250 255

Tyr Ile Thr Cys His Leu Lys Val Thr Leu Ala Glu Gln Asp Pro Asp

260 265 270

Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys Pro Ser Asn Ser Trp Phe

275 280 285

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

290 295 300

Cys Gly Thr Pro Ser His Ser Arg Arg Gln Pro His Val Met Ser Gln

305 310 315 320

Trp Ser Arg Ser Ala Ser Arg Asn

325

<210> 6

<211> 9

<212> Protein

<213> Homo sapiens

<400> 6

His Pro Glu Thr Ser Val Gln Pro Val

15

<210> 7

<211> 9

<212> Protein

<213> Homo sapiens

<400> 7

Pro Glu Thr Ser Val Gln Pro Val Leu

15

<210> 8

<211> 9

<212> Protein

<213> Homo sapiens

<400> 8

Gln Glu Ala Thr Leu Met Val Met Val

15

<210> 9

<211> 9

<212> Protein

<213> Homo sapiens

<400> 9

Ala Thr Leu Met Val Met Val Ser Lys

15

<210> 10

<211> 9

<212> Protein

<213> Homo sapiens

<400> 10

Leu Ile Arg Ala Ala Asp Leu Thr Leu

15

<210> 11

<211> 9

<212> Protein

<213> Homo sapiens

<400> 11

Thr Glu Asp Val Val Arg Phe Glu Val

15

<210> 12

<211> 9

<212> Protein

<213> Homo sapiens

<400> 12

Gln Val Thr Asp Asp Ala Leu Val Tyr

15

<210> 13

<211> 9

<212> Protein

<213> Homo sapiens

<400> 13

Ala Leu Val Tyr Ser Thr Phe Leu Leu

15

<210> 14

<211> 9

<212> Protein

<213> Homo sapiens

<400> 14

Phe Leu Leu His Asp Pro Arg Pro Val

15

<210> 15

<211> 9

<212> Protein

<213> Homo sapiens

<400> 15

Arg Pro Val Gly Asn Leu Ser Ile Val

15

<210> 16

<211> 9

<212> Protein

<213> Homo sapiens

<400> 16

Tyr Pro Arg Gln Gly Asn Val Ser Ser

15

<210> 17

<211> 9

<212> Protein

<213> Homo sapiens

<400> 17

Ser Ser Gln Ala Ile Leu Pro Thr Trp

15

<210> 18

<211> 9

<212> Protein

<213> Homo sapiens

<400> 18

Ala Ile Leu Pro Thr Trp Leu Pro Phe

15

<210> 19

<211> 9

<212> Protein

<213> Homo sapiens

<400> 19

Trp Leu Pro Phe Arg Thr Thr Val Phe

15

<210> 20

<211> 9

<212> Protein

<213> Homo sapiens

<400> 20

Val Phe Ser Glu Glu Lys Leu Thr Phe

15

<210> 21

<211> 9

<212> Protein

<213> Homo sapiens

<400> 21

Ser Glu Glu Lys Leu Thr Phe Ser Leu

15

<210> 22

<211> 9

<212> Protein

<213> Homo sapiens

<400> 22

Arg Leu Met Glu Glu Asn Trp Asn Ala

15

<210> 23

<211> 9

<212> Protein

<213> Homo sapiens

<400> 23

Phe His Leu Gly Asp Ala Ala His Leu

15

<210> 24

<211> 9

<212> Protein

<213> Homo sapiens

<400> 24

Ile His Thr Gly Ser His Val Pro Leu

15

<210> 25

<211> 9

<212> Protein

<213> Homo sapiens

<400> 25

Ser Pro Tyr His Thr Ile Val Asp Phe

15

<210> 26

<211> 9

<212> Protein

<213> Homo sapiens

<400> 26

Gly Leu Thr Asp Ala Ser Ser Ala Phe

15

<210> 27

<211> 9

<212> Protein

<213> Homo sapiens

<400> 27

Leu Thr Asp Ala Ser Ser Ala Phe Lys

15

<210> 28

<211> 9

<212> Protein

<213> Homo sapiens

<400> 28

Val Pro Arg Pro Gly Pro Asp Thr Leu

15

<210> 29

<211> 9

<212> Protein

<213> Homo sapiens

<400> 29

Arg Pro Gly Pro Asp Thr Leu Gln Phe

15

<210> 30

<211> 9

<212> Protein

<213> Homo sapiens

<400> 30

Gln Phe Thr Val Asp Val Phe His Phe

15

<210> 31

<211> 9

<212> Protein

<213> Homo sapiens

<400> 31

Phe Thr Val Asp Val Phe His Phe Ala

15

<210> 32

<211> 9

<212> Protein

<213> Homo sapiens

<400> 32

Ala Asn Asp Ser Arg Asn Met Ile Tyr

15

<210> 33

<211> 9

<212> Protein

<213> Homo sapiens

<400> 33

Met Ile Tyr Ile Thr Cys His Leu Lys

15

<210> 34

<211> 9

<212> Protein

<213> Homo sapiens

<400> 34

Ile Tyr Ile Thr Cys His Leu Lys Val

15

<210> 35

<211> 9

<212> Protein

<213> Homo sapiens

<400> 35

Phe Ser Lys Pro Ser Asn Ser Trp Phe

15

<210> 36

<211> 9

<212> Protein

<213> Homo sapiens

<400> 36

Lys Pro Ser Asn Ser Trp Phe Pro Val

15

<210> 37

<211> 9

<212> Protein

<213> Homo sapiens

<400> 37

Arg Gln Pro His Val Met Ser Gln Trp

15

<210> 38

<211> 9

<212> Protein

<213> Homo sapiens

<400> 38

Arg Gly Asp His Glu Val Glu Gln Trp

15

<210> 39

<211> 9

<212> Protein

<213> Homo sapiens

<400> 39

Glu Ala Thr Leu Met Val Met Val Ser

15

<210> 40

<211> 9

<212> Protein

<213> Homo sapiens

<400> 40

Leu Met Val Met Val Ser Lys Asp Leu

15

<210> 41

<211> 9

<212> Protein

<213> Homo sapiens

<400> 41

Met Val Met Val Ser Lys Asp Leu Phe

15

<210> 42

<211> 9

<212> Protein

<213> Homo sapiens

<400> 42

Leu Ile Arg Ala Ala Asp Leu Thr Leu

15

<210> 43

<211> 9

<212> Protein

<213> Homo sapiens

<400> 43

Leu Val Met Ser Asp Thr Glu Asp Val

15

<210> 44

<211> 9

<212> Protein

<213> Homo sapiens

<400> 44

Val Ser Met Asp Thr Glu Asp Val Val

15

<210> 45

<211> 9

<212> Protein

<213> Homo sapiens

<400> 45

Val Val Arg Phe Glu Val Gly Leu His

15

<210> 46

<211> 9

<212> Protein

<213> Homo sapiens

<400> 46

Gln Val Thr Asp Asp Ala Leu Val Tyr

15

<210> 47

<211> 9

<212> Protein

<213> Homo sapiens

<400> 47

Ala Leu Val Tyr Ser Thr Phe Leu Leu

15

<210> 48

<211> 9

<212> Protein

<213> Homo sapiens

<400> 48

Leu Val Tyr Ser Thr Phe Leu Leu His

15

<210> 49

<211> 9

<212> Protein

<213> Homo sapiens

<400> 49

Phe Leu Leu Asp Pro His Arg Pro Val

15

<210> 50

<211> 9

<212> Protein

<213> Homo sapiens

<400> 50

Leu Leu His Asp Pro Arg Pro Val Gly

15

<210> 51

<211> 9

<212> Protein

<213> Homo sapiens

<400> 51

Leu Ser Ile Val Arg Thr Asn Arg Ala

15

<210> 52

<211> 9

<212> Protein

<213> Homo sapiens

<400> 52

Ile Val Arg Thr Asn Arg Ala Glu Ile

15

<210> 53

<211> 9

<212> Protein

<213> Homo sapiens

<400> 53

Pro Phe Arg Thr Thr Val Phe Ser Glu

15

<210> 54

<211> 9

<212> Protein

<213> Homo sapiens

<400> 54

Phe Arg Thr Thr Val Phe Ser Glu Glu

15

<210> 55

<211> 9

<212> Protein

<213> Homo sapiens

<400> 55

Thr Phe Ser Leu Arg Leu Met Glu Glu

15

<210> 56

<211> 9

<212> Protein

<213> Homo sapiens

<400> 56

Phe His Leu Gly Asp Ala Ala His Leu

15

<210> 57

<211> 9

<212> Protein

<213> Homo sapiens

<400> 57

Leu Arg Leu Phe Val Asp His Cys Val

15

<210> 58

<211> 9

<212> Protein

<213> Homo sapiens

<400> 58

Leu Phe Val Asp His Cys Val Ala Thr

15

<210> 59

<211> 9

<212> Protein

<213> Homo sapiens

<400> 59

Gln Phe Thr Val Asp Val Phe His Phe

15

<210> 60

<211> 9

<212> Protein

<213> Homo sapiens

<400> 60

Phe Ala Asn Asp Ser Asn Arg Met Ile

15

<210> 61

<211> 9

<212> Protein

<213> Homo sapiens

<400> 61

Ile Tyr Ile Thr Cys His Leu Lys Val

15

<210> 62

<211> 9

<212> Protein

<213> Homo sapiens

<400> 62

Val Met Ser Gln Trp Ser Arg Ser Ala

15

<210> 63

<211> 9

<212> Protein

<213> Homo sapiens

<400> 63

Trp Ser Arg Ser Ala Ser Arg Asn Arg

15

<210> 64

<211> 9

<212> Protein

<213> Homo sapiens

<400> 64

Leu Ile Phe Leu Asp Arg Arg Gly Asp

15

<210> 65

<211> 9

<212> Protein

<213> Homo sapiens

<400> 65

Ile Phe Leu Asp Arg Arg Gly Asp His

15

<210> 66

<211> 49

<212> Protein

<213> Homo sapiens

<400> 66

Gly Gly Ala Ser His Pro Glu Thr Ser Val Gln Pro Val Leu Val Glu

1 5 10 15

Cys Gln Glu Ala Thr Leu Met Val Met Val Ser Lys Asp Leu Phe Gly

20 25 30

Thr Gly Lys Leu Ile Arg Ala Ala Asp Leu Thr Leu Gly Pro Glu Ala

35 40 45

Cys

<210> 67

<211> 26

<212> Protein

<213> Homo sapiens

<400> 67

Glu Ala Cys Glu Pro Leu Val Ser Met Asp Thr Glu Asp Val Val Arg

1 5 10 15

Phe Glu Val Gly Leu His Glu Cys Gly Asn

20 25

<210> 68

<211> 43

<212> Protein

<213> Homo sapiens

<400> 68

Cys Gly Asn Ser Met Gln Val Thr Asp Asp Ala Leu Val Tyr Ser Thr

1 5 10 15

Phe Leu Leu His Asp Pro Arg Pro Val Gly Asn Leu Ser Ile Val Arg

20 25 30

Thr Asn Arg Ala Glu Ile Pro Ile Glu Cys Arg

35 40

<210> 69

<211> 50

<212> Protein

<213> Homo sapiens

<400> 69

Ile Glu Cys Arg Tyr Pro Arg Gln Gly Asn Val Ser Ser Gln Ala Ile

1 5 10 15

Leu Pro Thr Trp Leu Pro Phe Arg Thr Thr Val Phe Ser Glu Glu Lys

20 25 30

Leu Thr Phe Ser Leu Arg Leu Met Glu Glu Asn Trp Asn Ala Glu Lys

35 40 45

Arg Ser

50

<210> 70

<211> 41

<212> Protein

<213> Homo sapiens

<400> 70

Lys Arg Ser Pro Thr Phe His Leu Gly Asp Ala Ala His Leu Gln Ala

1 5 10 15

Glu Ile His Thr Gly Ser His Val Pro Leu Arg Leu Phe Val Asp His

20 25 30

Cys Val Ala Thr Pro Thr Pro Asp Gln

35 40

<210> 71

<211> 44

<212> Protein

<213> Homo sapiens

<400> 71

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

1 5 10 15

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

20 25 30

Pro Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val

35 40

<210> 72

<211> 34

<212> Protein

<213> Homo sapiens

<400> 72

Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn

1 5 10 15

Asp Ser Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu

20 25 30

Ala Glu

<210> 73

<211> 20

<212> Protein

<213> Homo sapiens

<400> 73

Lys Ala Cys Ser Phe Ser Lys Pro Ser Asn Ser Trp Phe Pro Val Glu

1 5 10 15

Gly Pro Ala Asp

20

<210> 74

<211> 27

<212> Protein

<213> Homo sapiens

<400> 74

Ser His Ser Arg Arg Gln Pro His Val Met Ser Gln Trp Ser Arg Ser

1 5 10 15

Ala Ser Arg Asn Arg Arg His Val Thr Glu Glu

20 25

<210> 75

<211> 26

<212> Protein

<213> Homo sapiens

<400> 75

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

1 5 10 15

His Glu Val Glu Gln Trp Ala Leu Pro Ser

20 25

<210> 76

<211> 9

<212> Protein

<213> Homo sapiens

<400> 76

Phe Leu Leu His Asp Pro Arg Pro Val

15

<210> 77

<211> 9

<212> Protein

<213> Homo sapiens

<400> 77

Arg Leu Met Glu Glu Asn Trp Asn Ala

15

<210> 78

<211> 9

<212> Protein

<213> Homo sapiens

<400> 78

Ala Leu Val Tyr Ser Thr Phe Leu Leu

15

<210> 79

<211> 9

<212> Protein

<213> Homo sapiens

<400> 79

Phe Thr Val Asp Val Phe His Phe Ala

15

<210> 80

<211> 10

<212> Protein

<213> Homo sapiens

<400> 80

Leu Arg Leu Met Glu Glu Asn Trp Asn Ala

1 5 10

<210> 81

<211> 10

<212> Protein

<213> Homo sapiens

<400> 81

Phe Leu Asp Arg Arg Gly Asp His Glu Val

1 5 10

<210> 82

<211> 9

<212> Protein

<213> Homo sapiens

<400> 82

Cys Leu Val Asp Gly Leu Thr Asp Ala

15

<210> 83

<211> 9

<212> Protein

<213> Homo sapiens

<400> 83

Asn Met Ile Tyr Ile Thr Cys His Leu

15

<210> 84

<211> 10

<212> Protein

<213> Homo sapiens

<400> 84

Thr Phe Leu Leu His Asp Pro Arg Pro Val

1 5 10

<210> 85

<211> 10

<212> Protein

<213> Homo sapiens

<400> 85

Lys Leu Ile Arg Ala Ala Asp Leu Thr Leu

1 5 10

<---

Claims (29)

1. Pharmaceutical composition for use in a method for therapeutic or prophylactic treatment, or for diagnosing lung cancer expressing the ZP3 protein and/or its metastases in humans, where the composition contains: an immunogenic polypeptide source comprising at least one of class I and class II MHC-restricted epitopes from the human zona pellucida 3 (hZP3) amino acid sequence, and at least one excipient, wherein the immunogenic polypeptide source is a composition comprising: a) a protein composition comprising at least one immunogenic peptide comprising or consisting of the amino acid sequence of SEQ ID NO: 83 and at least one excipient, b) a nucleic acid molecule encoding the amino acid sequence of said immunogenic polypeptide; and/or c) a cell expressing said immunogenic polypeptide. 2. Pharmaceutical composition for use according to claim 1, where the source of the immunogenic polypeptide is a composition containing a) a protein composition further comprising all of the immunogenic peptides comprising or consisting of the amino acid sequences of SEQ ID NOs: 79, 80, 81 and 84; b) one or more nucleic acid molecules encoding the amino acid sequence of said immunogenic polypeptides; and/or c) a cell expressing said immunogenic polypeptides. 3. Pharmaceutical composition for use according to claim 1 or 2, where a) the protein composition further comprises one or more immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 66-75; and/or one or more immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 76-78, 82 and 85, and wherein the one or more immunogenic peptides optionally further comprise an MHC class II restricted epitope from an amino acid hZP3 protein sequences; b) one or more nucleic acid molecules further encode the amino acid sequence of one or more immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 66-75 and/or one or more immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 76-78, 82, and 85, and wherein the one or more immunogenic peptides optionally further comprise an MHC class II restricted epitope from the amino acid sequence of the hZP3 protein; and/or c) the cell further expresses one or more immunogenic peptides comprising or consisting of an amino acid sequence selected from SEQ ID NOs: 66-75 and/or one or more immunogenic peptides containing or consisting of an amino acid sequence selected from SEQ ID NOs: 76-78, 82 and 85, and wherein the one or more immunogenic peptides optionally further comprise an MHC class II restricted epitope from the amino acid sequence of the hZP3 protein. 4. Pharmaceutical composition for use according to any one of paragraphs. 1-3, wherein the method of treatment is a method for preventing metastasis and/or recurrence of lung cancer, wherein preferably the lung cancer is non-small cell lung cancer. 5. Pharmaceutical composition for use according to any one of paragraphs. 1-4, where the method of treatment is combined with immunomodulatory therapy, surgery, radiation therapy, chemotherapy, targeted therapy, or a combination thereof. 6. A pharmaceutical composition for use according to claim 5, wherein the immunomodulatory therapy comprises the use of at least one of a checkpoint inhibitor, an antibody targeting a member of the TNF receptor family, an immunosuppressive cytokine, a γC cytokine, a TLR agonist, and an iNKT cell agonist. 7. Pharmaceutical composition for use according to any one of paragraphs. 1-6 where: a) the protein composition contains at least one immunogenic polypeptide, as specified in any one of paragraphs. 1-3, comprising a contiguous amino acid sequence of at least 18 amino acids selected from the hZP3 amino acid sequence, and wherein the contiguous amino acid sequence contains at least one of MHC class I and MHC class II T-cell epitopes; b) the nucleic acid molecule is: i) a DNA molecule which is an expression construct for the expression of said immunogenic polypeptide in a human cell; or ii) an RNA molecule that can be translated into said immunogenic polypeptide in a human cell; c) the cell is a microbial cell, preferably a Listeria cell. 8. Pharmaceutical composition for use according to claim 7, wherein the protein composition contains more than one different immunogenic polypeptide, each of which contains a contiguous amino acid sequence of at least 18 amino acids selected from the hZP3 amino acid sequence, and has a length in the range of 18-100 amino acids , preferably a length in the range of 18-60 amino acids. 9. Pharmaceutical composition for use according to any one of the preceding claims, wherein hZP3 contains the sequence of SEQ ID NO: 5. 10. A pharmaceutical composition for use according to any one of the preceding claims, wherein the source of one or more immunogenic peptides collectively comprises at least one of: a) at least 50%, 70%, 80%, 90% or 95% of the complete hZP3 amino acid sequence or the amino acid sequence of amino acids 23-350 in SEQ ID NO: 3; And b) at least 50%, 70%, 80%, 90% or 95% of the potential MHC I and/or MHC II epitopes predicted by a computer algorithm bioinformatics tool. 11. A pharmaceutical composition for use according to any one of the preceding claims, wherein the method further comprises administering, preferably co-administering, at least one adjuvant. 12. A pharmaceutical composition for use according to any of the preceding claims, wherein the method of treatment comprises administering an effective amount of the composition, wherein the composition is administered by at least one of the intratumoral, intramuscular, intraperitoneal, intradermal, subcutaneous, transdermal routes of administration, and administration to an anatomical site that drains into at least one lymphatic collector.

Images