Influenza b virus vaccines and uses thereof

Abstract

Provided herein are isolated mutant influenza hemagglutinin polypeptides, methods for providing isolated mutant influenza hemagglutinin polypeptides, methods for using the isolated mutant influenza hemagglutinin polypeptides as diagnostics or for isolating antibodies, compositions comprising the isolated mutant influenza hemagglutinin polypeptides, methods for preparing the isolated mutant influenza hemagglutinin polypeptides, and methods for preparing the isolated mutant influenza hemagglutinin polypeptides. Vaccines comprising these isolated mutant influenza hemagglutinin polypeptides and methods of their use, particularly in the detection, prevention and / or treatment of influenza.

Description

[0001] Introduction

[0002] The present invention relates to the field of medicine. Provided herein are isolated influenza hemagglutinin polypeptides, methods for providing hemagglutinin polypeptides of type B, compositions comprising such hemagglutinin polypeptides, vaccines comprising such hemagglutinin polypeptides, and methods of using them, particularly for use in the detection, prevention, and / or treatment of influenza B. Background Art

[0003] Influenza A and B viruses are major human pathogens that cause respiratory diseases (commonly referred to as "influenza" or "the flu"), the severity of which ranges from subclinical infection to primary viral pneumonia that can be fatal. The WHO estimates that influenza epidemics result in approximately one billion infections, three to five million severe cases, and 300,000 to 500,000 deaths each year. The severity of a pandemic influenza depends on multiple factors, including the virulence of the pandemic virus strain and the level of pre-existing immunity. The most severe influenza pandemic, which occurred in 1918, resulted in >40 million deaths globally. Influenza vaccines are formulated each year to match the circulating strains because they can be antigenically variable due to antigenic drift. Nevertheless, vaccine efficacy is not optimal, and it is very low in cases where there is an antigenic mismatch between the vaccine and the circulating virus strain. Antiviral agents targeting the influenza virus enzyme neuraminidase have been developed for prevention and treatment. However, the use of these antiviral drugs remains limited. Emerging approaches to combating influenza include the development of universal influenza virus vaccines that provide protection against antigenically distant influenza viruses (1).

[0004] Over the past three decades, two distinct lineages of influenza B have co-circulated in the population to varying degrees each season, and the lineage of influenza B that has predominated in a given season has proven difficult to predict, complicating the decision of which lineage to include in the trivalent influenza vaccine (TIV) ((2); US Centers for Disease Control and Prevention, “Seasonal influenza activity surveillance reports 2001 - 2018” [US Centers for Disease Control and Prevention, “2001 - 2018 Seasonal Influenza Activity Surveillance Reports”] www.cdc.gov / flu / weekly / pastreports.htm (accessed July 2, 2018); European Centre for Disease Prevention and Control / WHO Regional Office for Europe, “Annual epidemiological reports on seasonal influenza 2001 - 2018” [European Centre for Disease Prevention and Control / WHO Regional Office for Europe, “2001 - 2018 Annual Epidemiological Reports on Seasonal Influenza”], ecdc.europa.eu / en / seasonal-influenza / surveillance-and-disease-data / aer (accessed July 2, 2018)). The importance of effective coverage of influenza B by vaccination is reflected in its contribution to the overall burden of seasonal influenza.According to data from the US Centers for Disease Control and reports from several European countries, between 2001 and 2018, influenza B accounted for 0.8%-82% of the total number of laboratory-confirmed influenza cases, with a seasonal average of 25% ((2); US Centers for Disease Control and Prevention, “Seasonal influenza activity surveillance reports 2001-2018” [www.cdc.gov / flu / weekly / pastreports.htm (accessed July 2, 2018)]; European Centre for Disease Prevention and Control / WHO Regional Office for Europe, “Annual epidemiological reports on seasonal influenza 2001-2018” [ecdc.europa.eu / en / seasonal-influenza / surveillance-and-disease-data / aer (accessed July 2, 2018)]; (3); (4)). In addition, influenza B is a major contributor to overall morbidity and mortality attributable to influenza, with an attributable hospitalization rate similar to that of influenza A / H3N2 and higher than that of A / H1N1 (Thompson et al., JAMA [Journal of the American Medical Association] 292:1333-40 (2004)), accounting for 15% of all influenza-attributable respiratory and circulatory-related deaths in the United States and 34% among pediatric patients (Ambrose et al., Hum. Vaccin. Immunother. [Human Vaccines & Immunotherapeutics] 8:81-8 (2012); (5)).These principles have led multiple health authorities, including the World Health Organization and the US Advisory Committee on Immunization Practices, to recommend quadrivalent influenza vaccines (QIVs) containing two influenza B antigens (one from each of the two influenza B lineages) as one of the options for seasonal vaccination ((6); (7); World Health Organization, “Recommended composition of influenza virus vaccines for use in the 2017-2018 northern hemisphere influenza season”, www.who.int / influenza / vaccines / virus / recommendations / 2018_19_north / en (accessed July 2, 2018)).

[0005] Influenza B virus strains are found almost exclusively in humans. Antigenic variation in HA within influenza B virus strains is less than that observed within influenza A strains. Two genetically and antigenically distinct lineages of influenza B virus circulate in humans, represented by the B / Yamagata / 16 / 88 (also known as B / Yamagata) and B / Victoria / 2 / 87 (B / Victoria) lineages (8). Although the disease spectrum caused by influenza B virus is generally less severe than that caused by influenza A virus, severe disease requiring hospitalization is still frequently observed in the case of influenza B infection.

[0006] Antibodies known to neutralize influenza virus are directed primarily against hemagglutinin (HA). Hemagglutinin or HA is a trimeric glycoprotein that is anchored to the viral envelope and has a dual function: it is responsible for binding to the cell surface receptor sialic acid, and following uptake it mediates fusion of the virus with the endosomal membrane, resulting in the release of viral RNA into the cytosol of the cell. HA contains a large head domain and a smaller stem domain. Attachment to the viral membrane is mediated by a C-terminal anchor sequence that is linked to the stem domain. The protein is post-translationally cleaved within a designated loop to produce two polypeptides: HA1 and HA2 (the full sequence is designated HA0). The membrane-distal head region is derived primarily from HA1, while the membrane-proximal stem region is derived primarily from HA2.

[0007] For most established vaccine platforms and new approaches, the expression of high-quality antigens in their most relevant conformation is a key success factor. The production of influenza vaccines can be challenging due to the unstable quaternary structure and low expression levels of HA (9). Stress conditions such as heat or long-term storage can reduce the potency of protein-based vaccines, and stability improvements can extend the vaccine shelf life and alleviate cold-chain issues often encountered in remote or poorer regions of the world. The HA stability and the pH value triggering conformational transformation vary between strains, and few stabilizing mutations have been identified (WO2021 / 074286). Since the conformational change of influenza B HA is triggered by low pH, the removal of the pH-triggering switch can improve pH stability, and it has been shown to also improve overall HA stability. Although native influenza HA is cleaved into HA1 and HA2 polypeptides, this cleavage does not occur in typical protein expression systems, so proteolytic enzymes such as trypsin are added to cleave the precursor HA0 into HA1 and HA2. Although the cleaved protein is able to fold into a mature and stable trimeric conformation, it does become sensitive to low-pH-triggered conformational changes. Therefore, the cleavage of HA should occur after it has been transported through the low-pH cellular compartment.

[0008] Accordingly, there is a need to develop a strategy that provides methods for obtaining high-quality reagents for diagnosis, isolation of B cells and mAbs, and potent reagents for influenza structural studies. Most importantly, stabilizing HA can improve the developability and efficacy of influenza B vaccines based on various platforms. SUMMARY OF THE INVENTION

[0009] Provided herein are isolated mutant influenza hemagglutinin polypeptides, methods for providing these isolated hemagglutinin polypeptides, compositions comprising these isolated hemagglutinin polypeptides, vaccines comprising these isolated hemagglutinin polypeptides, and methods of using these compositions and vaccines.

[0010] Provided herein are isolated mutant influenza hemagglutinin polypeptides. The isolated mutant influenza hemagglutinin polypeptide comprises at least one stabilizing mutation in at least one of the unstable regions (a)-(e) in the polypeptide, wherein at least one stabilizing mutation comprises a substitution at the following positions: (a) amino acid positions 227, 229, and / or 238 in the head switch; and / or (b) amino acid positions 329 and / or 426 in the neck switch; and / or (c) amino acid positions 384, 402, 472, and / or 476 in the stalk switch; and / or (d) amino acid positions 468, 471, 475, or 478 in the repulsive three-fold axis cluster; and / or (e) amino acid positions 235, 430, and / or 433 in the hinge loop, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0011] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least two stabilizing mutations in at least two of the unstable regions (a)-(e) in the polypeptide.

[0012] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least two stabilizing mutations in two, three, four, or five of the unstable regions (a)-(e) in the polypeptide. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least three stabilizing mutations in three, four, or five of the unstable regions (a)-(e) in the polypeptide. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least four stabilizing mutations in four or five of the unstable regions (a)-(e) in the polypeptide. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least five stabilizing mutations in the five unstable regions (a)-(e) in the polypeptide.

[0013] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen stabilizing mutations.

[0014] In certain embodiments, (a) in the head switch, amino acid position 227 is substituted with an amino acid selected from the group consisting of T, L, R, Q, F, I, and Y; amino acid position 229 is substituted with amino acid L; and / or amino acid position 238 is substituted with amino acid F; and / or (b) in the neck switch, amino acid position 329 is substituted with an amino acid selected from the group consisting of M, W, and F, and / or amino acid position 426 is substituted with an amino acid selected from the group consisting of F, W, Y, and P; and / or (c) in the stem switch, amino acid position 384 is substituted with an amino acid selected from F or Y, amino acid position 402 is substituted with amino acid A, amino acid position 472 is substituted with an amino acid selected from the group consisting of W, R, F, K, or L, and / or amino acid position 476 is substituted with amino acid F; and / or (d) in the repulsion, amino acid position 468 is substituted with amino acid L; amino acid position 471 is substituted with an amino acid selected from V or Q; amino acid position 475 is substituted with an amino acid selected from the group consisting of Q, N, W, F, and L, or amino acid position 478 is substituted with an amino acid selected from W or R; and / or (e) in the hinge loop, amino acid position 235 is substituted with amino acid W; amino acid position 430 is substituted with an amino acid selected from L or Y; and / or amino acid position 433 is substituted with amino acid P.

[0015] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises an amino acid sequence wherein (a) amino acid position 384 is replaced by F and amino acid position 475 is replaced by W; (b) amino acid position 384 is replaced by F and amino acid position 475 is replaced by Q; (c) amino acid position 384 is replaced by F, amino acid position 402 is replaced by A, amino acid position 472 is replaced by K, and amino acid position 476 is replaced by F; (d) amino acid position 384 is replaced by F, amino acid position 402 is replaced by A, amino acid position 472 is replaced by R, and amino acid position 476 is replaced by F; (e) amino acid position 384 is replaced by Y, amino acid position 402 is replaced by A, amino acid position 472 is replaced by R, and amino acid position 476 is replaced by F; (f) amino acid position 476 is replaced by F and amino acid position 475 is replaced by W; (g) amino acid position 476 is replaced by F and amino acid position 475 is replaced by Q; (h) amino acid position 227 is replaced by T and amino acid position 426 is replaced by Y; (i) amino acid position 227 is replaced by T and amino acid position 430 is replaced by Y; (j) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 430 is replaced by Y; (k) amino acid position 227 is replaced by T and amino acid position 475 is replaced by W; (l) amino acid position 227 is replaced by T and amino acid position 475 is replaced by Q; (m) amino acid position 227 is replaced by T and amino acid position 384 is replaced by F; (n) amino acid position 227 is replaced by T and amino acid position 476 is replaced by F; (o) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 475 is replaced by W; (p) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 475 is replaced by Q; (q) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 475 is replaced by W, and amino acid position 430 is replaced by Y; (r) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 475 is replaced by Q, and amino acid position 430 is replaced by Y; (s) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 384 is replaced by F; (t) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, and amino acid position 475 is replaced by W; (u) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, amino acid position 475 is replaced by W, and amino acid position 430 is replaced by Y; (v) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, and amino acid position 475 is replaced by Q;(w) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y; (x) The amino acid at position 227 is replaced by T and the amino acid at position 235 is replaced by W; (y) The amino acid at position 475 is replaced by W and the amino acid at position 426 is replaced by Y; (z) The amino acid at position 475 is replaced by W and the amino acid at position 430 is replaced by Y; (aa) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by R; (bb) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by F; (cc) The amino acid at position 426 is replaced by Y and the amino acid at position 384 is replaced by F; (dd) The amino acid at position 426 is replaced by Y and the amino acid at position 476 is replaced by F; (ee) The amino acid at position 426 is replaced by Y and the amino acid at position 455 is replaced by A; (ff) The amino acid at position 426 is replaced by Y and the amino acid at position 329 is replaced by W; (gg) The amino acid at position 430 is replaced by Y and the amino acid at position 384 is replaced by F; (hh) The amino acid at position 430 is replaced by Y and the amino acid at position 476 is replaced by F; (ii) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by Y; (jj) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by W; (kk) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by F; (ll) The amino acid at position 433 is replaced by P and the amino acid at position 430 is replaced by Y; (mm) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by Y; (nn) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by W; (oo) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by F; (pp) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W; (qq) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (rr) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by F, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R; (ss) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R;(tt) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, and the amino acid at position 476 is replaced by F; (uu) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by L, and the amino acid at position 478 is replaced by R; (vv) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by Q; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by Q, and the amino acid at position 478 is replaced by R; (ww) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by K, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (xx) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by L, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (yy) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 471 is replaced by Q, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (zz) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (aaa) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, and the amino acid at position 476 is replaced by F; or (bbb) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by R, the amino acid at position 475 is replaced by W, and the amino acid at position 476 is replaced by F.;

[0016] In certain embodiments, the mutant influenza hemagglutinin polypeptide further comprises an introduced cleavage site. The introduced cleavage site can be, for example, a furin cleavage site. The furin cleavage site can be introduced, for example, by mutating amino acid positions 359 - 361 of the polypeptide, or by an insertion at the amino terminus of amino acid position 362, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises an insertion at the carboxyl terminus of the RSV p27 peptide (SEQ ID NO:2) at amino acid position 362.

[0017] In certain embodiments, the amino acid at position 362 is substituted with Q.

[0018] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a deletion of the signal peptide at the amino terminus of the polypeptide. The signal peptide can comprise, for example, amino acid positions 1 - 15 of the polypeptide.

[0019] In certain embodiments, the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46 - 48, 63, 67 - 75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204 - 208, 216, 219 - 222. In certain embodiments, the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46 - 48, 63, 67 - 75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204 - 208, 216, 219 - 222, and the mutant influenza hemagglutinin polypeptide comprises a deletion of the signal peptide at the amino terminus of the polypeptide.

[0020] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a carboxyl (C) - terminal truncation starting at amino acid positions from amino acid 536 to amino acid position 585, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0021] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises at least one additional glycan motif in the head domain of the polypeptide. The glycan motif can comprise, for example, a substitution of an amino (N)-linked glycosylation motif at at least one amino acid position selected from the group consisting of: (a) 136 or 137, (b) 141, and (c) 151, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1. The glycan motif can comprise, for example, a substitution of the N-linked glycosylation motif at amino acid positions 136 and 141, 136 and 151, 137 and 141, 137 and 151, or 141 and 151. In certain embodiments, the glycan motif comprises a substitution of the N-linked glycosylation motif at amino acid positions 141 and 151.

[0022] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a receptor binding site mutation in the polypeptide. The receptor binding site mutation can comprise, for example, a mutation at an amino acid position selected from the group consisting of: (a) 175, (b) 219, (c) 257, and (d) 258, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1. In certain embodiments, (a) 175 is substituted with an amino acid selected from the group consisting of: F, W, and Y; (b) 219 is substituted with an amino acid selected from the group consisting of: F, W, Y, R, and E; (c) 257 is substituted with an amino acid selected from the group consisting of: E, D, V, F; or (d) 258 is substituted with an amino acid selected from the group consisting of: E, D, V, and F. In certain embodiments, (a) 175 is substituted with W, (b) 219 is substituted with E, (c) 257 is substituted with E, or (d) 258 is substituted with E.

[0023] Also provided is an isolated nucleic acid encoding the isolated mutant influenza hemagglutinin polypeptide described herein.

[0024] Also provided is an isolated vector comprising the isolated nucleic acid described herein.

[0025] Also provided is an isolated host cell comprising the vector described herein.

[0026] Also provided is a pharmaceutical composition comprising the isolated mutant influenza hemagglutinin polypeptide, the isolated mutant influenza hemagglutinin nucleic acid, and / or the isolated vector described herein and a pharmaceutically acceptable carrier.

[0027] Also provided are methods of inducing an immune response against influenza virus in a subject in need thereof. These methods comprise administering to the subject in need thereof the pharmaceutical composition described herein.

[0028] Also provided are methods of producing isolated mutant influenza hemagglutinin polypeptides. These methods include culturing the isolated host cells described herein under conditions capable of producing the mutant influenza hemagglutinin polypeptide, and recovering the mutant influenza hemagglutinin polypeptide from the isolated host cells or culture.

[0029] Also provided are methods of producing the pharmaceutical compositions described herein. These methods include combining the isolated mutant influenza polypeptide with a pharmaceutically acceptable carrier.

[0030] Various embodiments and uses of the polypeptides according to the invention will become apparent from the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The foregoing Summary of the Invention and the following detailed description of the preferred embodiments of the present patent application are better understood when read in conjunction with the accompanying drawings. However, it should be understood that the present patent application is not limited to the exact embodiments shown in the drawings.

[0032] Figures 1A - 1K The structure and design elements of the polypeptides of the invention are shown. Figure 1A .Three-dimensional representation of a polypeptide of the invention (representing the extracellular domain of influenza B HA; pdb ID 4NRJ, (10)), with black spheres indicating positions of substitutions in the labile region ( Figures 1B - 1F ) and three other regions ( Figures 1G - 1I ). The positions of substitutions in each region are shown in separate figures: head switch ( Figure 1B ), neck switch ( Figure 1C ), stem switch ( Figure 1D ), hinge loop ( Figure 1E ), repulsive threefold axis cluster ( Figure 1F ), fusion peptide ( Figure 1G ), receptor binding site ( Figure 1H ) and base ( Figure 1I ). Figure 1J .Schematic representation of a polypeptide UFV220265 (SEQ ID NO:73) of the invention with the indicated positions of substitutions; φ in this example the C-terminus is truncated after residue 536 (numbering refers to WT HA; SEQ ID NO:1). Figure 1K .Cleavable polypeptide in process; as numbered and mutated in ( Figure 1J ), a 27-residue peptide (SEQ ID NO:2) containing a polybasic cleavage site (underlined) was introduced.

[0033] Figure 2. Comparison of expression levels of single-chain (uncleaved) Flu B HA variants with substitutions in the receptor binding site (position 167); base (position 392); fusion peptide (positions 373, 377, 380 and 391); and instability regions: head switch (positions 227, 229, 231, 236, 238 and 277); neck switch (positions 329, 332, 426, 453 and 455); stem switch (positions 384, 402, 472, 473 and 476); hinge loop (positions 235, 429, 430 and 433); and exclusion cluster (positions 475 and 478). Analytical size exclusion chromatograms showing the amounts of trimer (T) and monomer (M) of the stable variant in the supernatant of HEK293 cells after transfection compared to wild-type Iowa Flu B HA (grey line, UFV212130). Reference trimer and monomer peak heights are indicated by dashed lines.

[0034] Figure 3 . Scatter plot representation of the data in Table 1; trimer peak area vs. trimer % and dot size represents temperature stability. Wild-type Iowa Flu B HA is highlighted (UFV212130, grey dot).

[0035] Figures 4A - 4E Comparison of expression levels of single-chain (uncleaved) Flu B HA variants with combinations of substitutions in the head switch, neck switch, stem switch, hinge loop, and exclusion cluster regions. Analytical size exclusion chromatograms show the amount of trimers (T) and monomers (M) of stable FluB HA variants in the supernatant of HEK293 cells after transfection compared to wild-type Iowa Flu B HA (grey line, UFV212130). Reference trimer and monomer peak heights are represented by dashed lines. Figure 4A , Figure 4B , Figure 4C , Figure 4D and Figure 4E .Combinations of mutations in one, two, three, four, and all five regions, respectively.

[0036] Figure 5 .Table 2 Scatter plot representation of data; trimer peak area vs. trimer % and dot size represents temperature stability. Wild-type Iowa Flu B HA is highlighted (UFV212130, gray dot in left center plot). Bottom plot shows legend for markers and provides explanation of combination of stable unstable regions.

[0037] Figures 6A - 6D . Figure 6ASEC analysis of two wt HAs (B / Victoria / 02 / 1987 and B / Guangdong / 120 / 2000) compared to the "repaired" variant HA is shown. According to Table 4, the repaired HA contains substitutions of very rare consensus residues. Figures 6B - 6D Comparison of the expression levels of single-stranded (uncut) and cleaved Flu B WT HA and stabilized HAs with different degrees of stability is shown: substitution groups A (K227T, H384F, Q426Y, G430Y, and E475W), B (K227T, H384F, and E475W), or C (H329W and Q426W) from B Iowa, B Ohio, B Brisbane, B Florida, and B Singapore. Figures 6B - 6C . Analytical size exclusion chromatograms show the amounts of trimer (T) and monomer (M) of stabilized single-stranded (uncut) Flu B HA ( Figure 6B ) and cleaved ( Figure 6C ) variants (stabilized variant group A black line, variant group B dotted line, and variant group C dashed line) in the supernatant of HEK293 cells after transfection compared to wild-type (gray line). Figure 6D . Western blot analysis shows the processing of stabilized HA (variant group A) in the presence and absence of the P27 peptide. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was run on the culture supernatant under reducing conditions, transferred to a blotting membrane, and the radiolabeled protein was visualized. The major bands correspond to uncut (HA0) and cleaved HA (HA2 chains).

[0038] Figure 7 . Comparison of the expression levels of cleaved Flu B HA variants with combinations of substitutions in five unstable regions (UFV220875) and additional substitutions in the stem-switch region and the repulsive three-fold axis cluster region. Analytical size exclusion chromatogram.

[0039] Figure 8 . Scatter plot representation of the data in Table 7 for polypeptide expression (>10 mAU*mL in the SEC plot); trimer peak area versus trimer %, and dot size represents temperature stability.

[0040] Figure 9 Alignment of UFV220265 (SEQ ID NO:73) and B / Brisbane / 60 / 08 (SEQ ID NO:1) is shown.

[0041] Definitions

[0042] Definitions of the terms used in the present invention are given below.

[0043] The amino acids according to the present invention can be any of the twenty naturally occurring (or "standard") amino acids or variants thereof. The standard amino acids can be grouped based on their properties. Important factors are charge, hydrophilicity or hydrophobicity, size, and functional groups. These properties are important for protein structure and protein-protein interactions. Some amino acids have special properties, such as cysteine, which can form covalent disulfide bonds (or disulfide bridges) with other cysteine residues; proline, which forms a loop with the polypeptide backbone; and glycine, which is more flexible than other amino acids. Table 1 shows the abbreviations and properties of the standard amino acids.

[0044] Table 1. Standard Amino Acids, Abbreviations, and Properties

[0045]

[0046]

[0047] The term "amino acid sequence identity" refers to the degree of identity or similarity between a pair of aligned amino acid sequences, usually expressed as a percentage. The percentage of identity is the percentage of amino acid residues in a candidate sequence that are the same (i.e., the amino acid residue at a given position in the alignment is the same residue) or similar (i.e., the amino acid substitution at a given position in the alignment is a conservative substitution, as discussed below) to the corresponding amino acid residues in a peptide after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percentage of sequence homology. Sequence homology (including the percentage of sequence identity and similarity) is determined using sequence alignment techniques well known in the art (such as by visual inspection and mathematical calculations), or more preferably, the comparison is done by using a computer program to compare sequence information. An exemplary preferred computer program is the Genetics Computer Group (GCG; Madison, Wis.) Wisconsin Package version 10.0 program, 'GAP' (11).

[0048] "Conservative substitution" refers to the replacement of an amino acid of one class with another amino acid of the same class. In certain embodiments, a conservative substitution does not change the structure or function of the polypeptide, or both. The classes of amino acids used for conservative substitution purposes include hydrophobic (e.g., Met, Ala, Val, Leu), neutral hydrophilic (e.g., Cys, Ser, Thr), acidic (e.g., Asp, Glu), basic (e.g., Asn, Gln, His, Lys, Arg), conformation breakers (e.g., Gly, Pro), and aromatic (e.g., Trp, Tyr, Phe).

[0049] As used herein, the terms "disease" and "disorder" are used interchangeably to refer to a medical condition of a subject. In some embodiments, the medical condition is a viral infection, particularly an influenza virus infection. In certain embodiments, the term "disease" refers to a pathological condition caused by the presence of a virus in a cell or subject or by the invasion of a virus into a cell or subject. In some embodiments, the medical condition is a disease of a subject, the severity of which is reduced by inducing an immune response in the subject via administration of an immunogenic composition.

[0050] As used herein, the term "effective amount" in the context of administering a therapy to a subject refers to an amount of the therapy that has one or more prophylactic and / or therapeutic effects. In some embodiments, the "effective amount" in the context of administering a therapy to a subject refers to an amount of the therapy that is sufficient to achieve a reduction or alleviation in the severity of an influenza B virus infection, a disease or symptom associated therewith, such as, but not limited to, reducing the duration of an influenza B virus infection, a disease or symptom associated therewith; preventing the progression of an influenza virus infection, a disease or symptom associated therewith; preventing the development, onset or recurrence of an influenza B virus infection, a disease or symptom associated therewith; preventing or reducing the transmission of an influenza virus from one subject to another; reducing hospitalization and / or length of hospitalization of a subject; increasing the survival of a subject with an influenza B virus infection or a disease associated therewith; eliminating an influenza B virus infection or a disease associated therewith; inhibiting or reducing influenza B virus replication; reducing influenza virus titer; and / or enhancing or improving one or more prophylactic or therapeutic effects of another therapy. In some embodiments, the effective amount does not result in complete protection against an influenza B virus disease, but does result in a reduction in the titer or amount of influenza B virus compared to an untreated subject. Benefits of reducing the titer, amount or total burden of influenza B virus include, but are not limited to, a reduction in the severity of infection symptoms, a reduction in infection symptoms and a shortening of the time to a disease associated with the infection.

[0051] As used herein, the term "host" is intended to refer to an organism or cell into which a vector, such as a cloning vector or expression vector, has been introduced. The organism or cell can be prokaryotic or eukaryotic. Preferably, the host includes an isolated host cell, such as a host cell in culture. The term "host cell" merely indicates that the cell has been modified for (over)expression of a polypeptide of the invention. It should be understood that the term host is intended to refer not only to a particular subject organism or cell, but also to progeny of such an organism or cell. Since certain modifications may occur in subsequent generations due to mutation or environmental influences, such progeny may in fact differ from the parental organism or cell, but are still included within the scope of the term "host" as used herein.

[0052] As used herein, the term "comprising" or "including" is considered to be followed by the phrase "but not limited to".

[0053] As used herein, the term "infection" means an invasion by an influenza virus through its reproduction and / or presence in a cell or a subject. In one embodiment, the infection is an "active" infection, i.e., an infection in which the virus replicates in the cell or the subject. Such an infection is characterized by the spread of the virus from the cells, tissues, and / or organs initially infected by the virus to other cells, tissues, and / or organs. The infection can also be a latent infection, i.e., an infection in which the virus does not replicate. In certain embodiments, an infection refers to a pathological condition caused by the presence of the virus in a cell or a subject or by the invasion of the virus into a cell or a subject.

[0054] Influenza viruses are classified into the following influenza virus types: type A, type B, and type C. The term "subtype" specifically includes all individual "strains" within each subtype, which are usually caused by mutations and exhibit different pathogenic profiles, including naturally occurring isolates as well as artificially created mutants or reassortants, etc. Such strains can also be referred to as various "isolates" of the virus subtype. Thus, as used herein, the terms "strain" and "isolate" can be used interchangeably. The current nomenclature for human influenza virus strains or isolates includes the type (genus) of the virus (i.e., type A, type B, or type C), the geographical location where it was first isolated, the strain number, and the year of isolation.

[0055] As used herein, the term "influenza virus disease" refers to a pathological condition caused by the presence of an influenza virus (e.g., influenza A or B virus) in a cell or a subject or by the invasion of an influenza virus into a cell or a subject. In a particular embodiment, the term refers to a respiratory disease caused by an influenza virus.

[0056] As used herein, the term "nucleic acid" is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), and analogs of DNA or RNA generated using nucleotide analogs. The nucleic acid can be single-stranded or double-stranded. As will be readily understood by one of ordinary skill in the art, nucleic acid molecules can be chemically or biochemically modified or can contain non-natural or derivatized nucleobases. Such modifications include, for example, labeling, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications (such as uncharged linkages (e.g., methyl phosphonate, phosphotriester, phosphoramidate, carbamate, etc.), charged linkages (e.g., phosphorothioate, dithiophosphonate, etc.)), side chain moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylating agents, and modified linkages (e.g., α-anomeric nucleic acids, etc.). Unless otherwise indicated, reference to a nucleic acid sequence encompasses its complementary sequence. Thus, reference to a nucleic acid molecule having a particular sequence should be understood to encompass its complementary strand having its complementary sequence. The complementary strand can also be used, for example, in antisense therapies, hybridization probes, and PCR primers.

[0057] As used herein, in certain embodiments, the numbering of amino acids in hemagglutinin is based on the numbering of amino acids in the hemagglutinin of wild-type influenza virus, e.g., the numbering of amino acids of influenza strain B / Brisbane / 60 / 08 (SEQ ID NO:1). As used in the present invention, the term "amino acid position "x"" thus means the amino acid corresponding to the amino acid at position x in the hemagglutinin of a particular wild-type influenza virus (e.g., B / Brisbane / 60 / 08 (SEQ ID NO:1)). One of skill in the art will understand that the B / Brisbane / 60 / 08 (SEQ ID NO:1) strain may contain more or fewer amino acids than other influenza strains and / or subtypes, and the equivalent amino acids in other influenza virus strains and / or subtypes can be determined by multiple sequence alignment with the B / Brisbane / 60 / 08 (SEQ ID NO:1) strain. By way of example, Figure 9Show the alignment of UFV220265 (SEQ ID NO:73) with wild-type B / Brisbane / 60 / 08 (SEQ ID NO:1). UFV220265 (SEQ ID NO:73) contains the following substitution mutations at positions K227T, H384F, Q426Y, G430Y and E475W of SEQ ID NO:1. Note that in the numbering system used throughout this application, 1 refers to the N-terminal amino acid of the immature hemagglutinin protein (SEQ ID NO:1). The mature sequence starts, for example, at position 16 of SEQ ID NO:1. Those skilled in the art will understand that the leader sequence (or signal sequence) that directs protein transport during production (such as the amino acids 1-15 corresponding to SEQ ID NO:1) is generally not present in the final polypeptide used, for example, in a vaccine. In certain embodiments, the polypeptides according to the invention thus comprise an amino acid sequence without a leader sequence, i.e., the amino acid sequence is based on the amino acid sequence of hemagglutinin without a signal sequence.

[0058] The terms "peptide", "polypeptide" or "protein" can refer to a molecule composed of amino acids and can be recognized as a protein by those skilled in the art. The conventional single-letter or three-letter codes for amino acid residues are used herein. The terms "peptide", "polypeptide" and "protein" are used interchangeably herein to refer to a polymer of amino acids of any length. The polymer can be linear or branched, it can contain modified amino acids, and it can be interspersed with non-amino acids. The term also encompasses amino acid polymers that have been modified either naturally or by intervention; natural or intervention modifications are, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation or any other manipulation or modification, such as conjugation with a labeled component. This definition also includes, for example, polypeptides containing one or more amino acid analogs (including, for example, non-natural amino acids, etc.) and other modifications known in the art.

[0059] The term "vector" denotes a nucleic acid molecule into which a second nucleic acid molecule can be inserted for introduction into a host and replication in that host, and in some cases expression. In other words, a vector is capable of transporting the nucleic acid molecule linked to it. The term "vector" as used herein encompasses cloning vectors as well as expression vectors. Vectors include, but are not limited to, plasmids, cosmids, bacterial artificial chromosomes (BACs) and yeast artificial chromosomes (YACs) and vectors derived from bacteriophages or plant or animal (including human) viruses. A vector contains an origin of replication recognized by the proposed host and, in the case of an expression vector, a promoter and other regulatory regions recognized by the host. Some vectors are capable of autonomous replication in the host into which they are introduced (for example, a vector having a bacterial origin of replication can replicate in bacteria). Other vectors can be integrated into the genome of the host cell after introduction, and thus replicate along with the host genome.

[0060] As used herein, the term "wild type" in the context of a virus refers to an influenza virus that is prevalent, naturally transmitted, and causes typical disease outbreaks.

[0061] As used herein, the term "glycan motif" or "N-linked glycosylation motif" refers to a specific amino acid motif of a polypeptide such that the specific amino acid motif can be glycosylated by the addition of a glycan molecule. The N-linked glycosylation motif contains the specific amino acid motif of NxT / S (where x is not P). In a polypeptide in which the N-linked glycosylation motif or glycan motif is substituted, the listed amino acid positions are related to the asparagine of the NxT / S amino acid motif. For example, in the following polypeptide, for positions 136, 137, and 151, N and T are introduced into the polypeptide, where N is introduced at positions 136, 137, and 151, respectively, and threonine is introduced at positions 138, 139, and 153, while for position 141, asparagine (N) is present in the wild-type sequence and the motif is completed by introducing threonine at position 143. Detailed Description

[0062] Influenza viruses have a major impact on global public health, causing millions of cases of severe illness, thousands of deaths, and significant economic losses each year.

[0063] Hemagglutinin (HA) is the major envelope glycoprotein from influenza viruses and is the main target of neutralizing antibodies. Hemagglutinin has two main functions during entry. First, hemagglutinin mediates the attachment of the virus to the surface of target cells through interaction with sialic acid receptors. Second, after viral endocytosis, hemagglutinin then triggers the fusion of the viral membrane with the endosomal membrane to release its genome into the cytoplasm of the target cell. HA contains a large extracellular domain of approximately 500 amino acids that is cleaved by a host-derived enzyme to produce two polypeptides that remain linked by a disulfide bond. Most of the N-terminal fragment (HA1, approximately 320 - 330 amino acids) forms the membrane-distal globular domain that contains the receptor-binding site and most of the determinants recognized by virus-neutralizing antibodies. The smaller C-terminal portion (HA2, approximately 180 amino acids) forms a stalk structure that anchors the globular domain to the cell membrane or viral membrane. The degree of sequence homology between HA1 polypeptides is less than that between HA2 polypeptides. The most conserved region is the sequence around the cleavage site, particularly the amino acids at the N-terminus of HA2, which is conserved among all influenza A and B virus subtypes. A portion of this region is exposed as a surface loop in the HA precursor molecule (HA0) but becomes inaccessible when HA0 is cleaved into HA1 and HA2 (12).

[0064] Isolated Mutant Hemagglutinin Polypeptides

[0065] To effect cleavage during the efficient production of recombinant Flu HA protein in a typical mammalian protein expression system, a strategy was designed to add a cleavage site that cleaves in a low pH environment adjacent to the HA cleavage site. Mammalian cells contain furin-like enzymes that are active at low pH. Thus, Flu HA with an additional engineered furin cleavage site in stable substitution combination with HA is a potential solution for high-level expression of HA in the correct native trimeric cleavage conformation. The introduction of a cleavage site that is cleaved during the production process is another reason for designing influenza HA proteins that are stable at low pH.

[0066] According to the present invention, novel isolated mutant hemagglutinin polypeptides with improved stability have been designed, which improve the developability of influenza B vaccines. In addition to an overall increase in stability, the mutant hemagglutinin shows a significant increase in stability at low pH. Thus, a stable HA with an engineered furin site can be cleaved in a low pH environment and expressed as a fully cleaved native HA trimer (a trimer of HA1 and HA2 dimers).

[0067] According to the present invention, compared to the amino acid sequence of the corresponding wild-type influenza virus hemagglutinin polypeptide (i.e., the influenza virus on which the mutant hemagglutinin polypeptide is based), the isolated mutant hemagglutinin polypeptide comprises one or more additional mutations, i.e., amino acid substitutions, in at least one, two, three, four, or five unstable regions (a)-(e), namely (a) the head switch ( Figure 1B ); (b) in the neck switch ( Figure 1C ); (c) in the stalk switch ( Figure 1D ); (d) the repulsive three-fold axis cluster ( Figure 1F ); and / or in (e) the hinge loop ( Figure 1E ).

[0068] The amino acid positions correspond to the amino acid sequence of SEQ ID NO:1 as provided herein. For example, an amino acid substitution at amino acid position 227 would correspond to an amino acid substitution of lysine (K) at position 227 of SEQ ID NO:1. As another example, an amino acid substitution at amino acid position 426 would correspond to an amino acid substitution of glutamine (Q) at position 426 of SEQ ID NO:1. The specific amino acid positions and residues can vary depending on the starting hemagglutinin polypeptide sequence of a particular influenza strain; however, one of ordinary skill in the art should be able to perform sequence alignments to identify the corresponding amino acid positions and residues that correspond to the positions on SEQ ID NO:1. The specific amino acid positions and residues can vary due to the insertion of a heterologous peptide (e.g., RSV p27 peptide) between HA1 and HA2 to optimize furin cleavage. Based on the sequence alignment, the identity of the amino acid positions and residues corresponds to the positions on SEQ ID NO:1.

[0069] In certain aspects of the invention, there are provided isolated mutant influenza hemagglutinin polypeptides. The isolated mutant influenza hemagglutinin polypeptide comprises at least one stabilizing mutation in at least one of the unstable regions (a)-(e) in the polypeptide, wherein the at least one stabilizing mutation comprises a substitution at the following positions: (a) amino acid positions 227, 229, and / or 238 in the head switch; and / or (b) amino acid positions 329 and / or 426 in the neck switch; and / or (c) amino acid positions 384, 402, 472, and / or 476 in the stalk switch; and / or (d) amino acid positions 468, 471, 475, or 478 in the repulsive three-fold axis cluster; and / or (e) amino acid positions 235, 430, and / or 433 in the hinge loop, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0070] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least two stabilizing mutations in at least one of the unstable regions (a)-(e) in the polypeptide, i.e., the isolated mutant influenza hemagglutinin polypeptide can comprise two stabilizing mutations in unstable region (a), or two stabilizing mutations in unstable region (b), or two stabilizing mutations in unstable region (c), or two stabilizing mutations in unstable region (d), or two stabilizing mutations in unstable region (e).

[0071] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least two stabilizing mutations in at least two of the two, three, four, or five destabilizing regions (a)-(e) in the polypeptide, i.e., at least two stabilizing mutations can be in at least two different destabilizing regions. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least three stabilizing mutations in at least three of the three, four, or five destabilizing regions (a)-(e) in the polypeptide, i.e., at least three stabilizing mutations can be in at least three different destabilizing regions. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least four stabilizing mutations in at least four of the four or five destabilizing regions (a)-(e) in the polypeptide, i.e., at least four stabilizing mutations can be in at least four different destabilizing regions. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises at least five stabilizing mutations in all five destabilizing regions (a)-(e) in the polypeptide, i.e., at least five stabilizing mutations can be in at least five different destabilizing regions.

[0072] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen stabilizing mutations.

[0073] In certain embodiments, (a) in the head switch, amino acid position 227 is substituted with an amino acid selected from the group consisting of T, L, R, Q, F, I, and Y; amino acid position 229 is substituted with amino acid L; and / or amino acid position 238 is substituted with amino acid F; and / or (b) in the neck switch, amino acid position 329 is substituted with an amino acid selected from the group consisting of M, W, and F, and / or amino acid position 426 is substituted with an amino acid selected from the group consisting of F, W, Y, and P; and / or (c) in the stem switch, amino acid position 384 is substituted with an amino acid selected from F or Y, amino acid position 402 is substituted with amino acid A, amino acid position 472 is substituted with an amino acid selected from the group consisting of W, R, F, K, or L, and / or amino acid position 476 is substituted with amino acid F; and / or (d) in the repulsion, amino acid position 468 is substituted with amino acid L; amino acid position 471 is substituted with an amino acid selected from V or Q; amino acid position 475 is substituted with an amino acid selected from the group consisting of Q, N, W, F, and L, or amino acid position 478 is substituted with an amino acid selected from W or R; and / or (e) in the hinge loop, amino acid position 235 is substituted with amino acid W; amino acid position 430 is substituted with an amino acid selected from L or Y; and / or amino acid position 433 is substituted with amino acid P.

[0074] In certain aspects of the present invention, the isolated mutant influenza hemagglutinin polypeptide comprises an amino acid sequence wherein (a) amino acid position 384 is replaced by F and amino acid position 475 is replaced by W; (b) amino acid position 384 is replaced by F and amino acid position 475 is replaced by Q; (c) amino acid position 384 is replaced by F, amino acid position 402 is replaced by A, amino acid position 472 is replaced by K, and amino acid position 476 is replaced by F; (d) amino acid position 384 is replaced by F, amino acid position 402 is replaced by A, amino acid position 472 is replaced by R, and amino acid position 476 is replaced by F; (e) amino acid position 384 is replaced by Y, amino acid position 402 is replaced by A, amino acid position 472 is replaced by R, and amino acid position 476 is replaced by F; (f) amino acid position 476 is replaced by F and amino acid position 475 is replaced by W; (g) amino acid position 476 is replaced by F and amino acid position 475 is replaced by Q; (h) amino acid position 227 is replaced by T and amino acid position 426 is replaced by Y; (i) amino acid position 227 is replaced by T and amino acid position 430 is replaced by Y; (j) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 430 is replaced by Y; (k) amino acid position 227 is replaced by T and amino acid position 475 is replaced by W; (l) amino acid position 227 is replaced by T and amino acid position 475 is replaced by Q; (m) amino acid position 227 is replaced by T and amino acid position 384 is replaced by F; (n) amino acid position 227 is replaced by T and amino acid position 476 is replaced by F; (o) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 475 is replaced by W; (p) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 475 is replaced by Q; (q) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 475 is replaced by W, and amino acid position 430 is replaced by Y; (r) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 475 is replaced by Q, and amino acid position 430 is replaced by Y; (s) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, and amino acid position 384 is replaced by F; (t) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, and amino acid position 475 is replaced by W; (u) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, amino acid position 475 is replaced by W, and amino acid position 430 is replaced by Y; (v) amino acid position 227 is replaced by T, amino acid position 426 is replaced by Y, amino acid position 384 is replaced by F, and amino acid position 475 is replaced by Q;(w) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y; (x) The amino acid at position 227 is replaced by T and the amino acid at position 235 is replaced by W; (y) The amino acid at position 475 is replaced by W and the amino acid at position 426 is replaced by Y; (z) The amino acid at position 475 is replaced by W and the amino acid at position 430 is replaced by Y; (aa) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by R; (bb) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by F; (cc) The amino acid at position 426 is replaced by Y and the amino acid at position 384 is replaced by F; (dd) The amino acid at position 426 is replaced by Y and the amino acid at position 476 is replaced by F; (ee) The amino acid at position 426 is replaced by Y and the amino acid at position 455 is replaced by A; (ff) The amino acid at position 426 is replaced by Y and the amino acid at position 329 is replaced by W; (gg) The amino acid at position 430 is replaced by Y and the amino acid at position 384 is replaced by F; (hh) The amino acid at position 430 is replaced by Y and the amino acid at position 476 is replaced by F; (ii) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by Y; (jj) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by W; (kk) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by F; (ll) The amino acid at position 433 is replaced by P and the amino acid at position 430 is replaced by Y; (mm) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by Y; (nn) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by W; (oo) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by F; (pp) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W; (qq) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (rr) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by F, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R; (ss) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R;(tt) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, and the amino acid at position 476 is replaced by F; (uu) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by L, and the amino acid at position 478 is replaced by R; (vv) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by Q; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by Q, and the amino acid at position 478 is replaced by R; (ww) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by K, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (xx) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by L, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (yy) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 471 is replaced by Q, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (zz) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by Q, and the amino acid at position 476 is replaced by F; (aaa) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, and the amino acid at position 476 is replaced by F; or (bbb) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by R, the amino acid at position 475 is replaced by W, and the amino acid at position 476 is replaced by F.;

[0075] In certain embodiments, the mutant influenza hemagglutinin polypeptide further comprises an introduced cleavage site. The introduced cleavage site can be, for example, a furin cleavage site. The furin cleavage site can allow for complete cleavage of HA to form a fully processed native trimer. The furin cleavage site can be introduced, for example, by mutating amino acid positions 359 - 361 of the polypeptide, or by an insertion at the amino terminus of amino acid position 362, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1. In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a modification of the cleavage site to a polybasic cleavage site or an insertion at the carboxyl terminus of the RSV p27 peptide (SEQ ID NO:2) at amino acid position 362 to allow for efficient processing by furin. The cleaved HA can form a fully processed native trimer.

[0076] In certain embodiments, the amino acid at position 362 is replaced with Q.

[0077] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a deletion of the signal peptide at the amino terminus of the polypeptide. The signal peptide can comprise, for example, amino acid positions 1 - 15 of the polypeptide.

[0078] In certain embodiments, the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46 - 48, 63, 67 - 75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204 - 208, 216, 219 - 222. In certain embodiments, the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46 - 48, 63, 67 - 75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204 - 208, 216, 219 - 222, and the mutant influenza hemagglutinin polypeptide comprises a deletion of the signal peptide at the amino terminus of the polypeptide.

[0079] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide is derived from the hemagglutinin of an influenza B virus. Specifically, the isolated mutant influenza hemagglutinin polypeptide can be derived from B / Yamagata / 16 / 1988 (also referred to as B / Yamagata); B / Singapore / INFTT-16-0610 / 2016 (B / Singapore), B / Florida / 04 / 2006 (B / Florida), B / Victoria / 2 / 1987 (B / Victoria); B / Iowa / 06 / 2017 (B / Iowa), B / Ohio / 01 / 2005 (B / Ohio), and / or B / Brisbane / 60 / 2008 (B / Brisbane) lineages.

[0080] In certain embodiments, the isolated mutant influenza hemagglutinin polypeptide further comprises a carboxyl (C)-terminal truncation starting at amino acid position 536 to amino acid position 585, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0081] The native form of influenza hemagglutinin (HA) exists as a trimer in the cell or viral membrane. In certain embodiments, the intracellular and transmembrane sequences are removed such that a secreted (soluble) polypeptide is produced upon expression in cells. Methods for expressing and purifying the secreted HA extracellular domain have been described (see, for example, (13); (14,15); (16,17); (18)). Those skilled in the art will understand that these methods can also be directly applied to the isolated mutant hemagglutinin polypeptides of the present invention in order to achieve the expression of secreted (soluble) polypeptides. Accordingly, these polypeptides are also encompassed by the present invention.

[0082] Optionally, for purification purposes, a his-tag sequence (HHHHHH (SEQ ID NO:134) or HHHHHHH (SEQ ID NO:135) or C-tag (SEQ ID NO:136)) can be linked to the (optionally truncated) isolated mutant hemagglutinin polypeptide, optionally, the his-tag sequence is linked via a linker. Optionally, the linker can contain a proteolytic cleavage site for enzymatic removal of the his-tag after purification.

[0083] To facilitate purification of the soluble form, a tag sequence can be added, such as a histidine tag (HHHHHH (SEQ ID NO:134) or HHHHHHH (SEQ ID NO:135)) or a FLAG tag (DYKDDDDK) (SEQ ID NO:137) or a C-tag (EPEA) (SEQ ID NO:136) or a combination thereof, optionally linked via a short linker. The linker can optionally contain a (partial) proteolytic cleavage site, such as IEGR (SEQ ID NO:138) (Factor X) or LVPRGS (SEQ ID NO:139) (thrombin), for subsequent processing according to protocols well known to those skilled in the art. The processed protein is also encompassed by the present invention.

[0084] These mutant influenza hemagglutinin polypeptides can be prepared according to any technique considered suitable by the skilled person, including the techniques described below.

[0085] Thus, the immunogenic polypeptides of the present invention can be synthesized as DNA sequences by standard methods known in the art, cloned using appropriate restriction enzymes and methods known in the art, and subsequently expressed in vitro or in vivo. Accordingly, the present invention also relates to nucleic acid molecules encoding the above polypeptides. The present invention further relates to vectors comprising a nucleic acid encoding a polypeptide of the present invention. In certain embodiments, the nucleic acid molecule according to the present invention is part of a vector (e.g., a plasmid). Such vectors can be readily manipulated by methods well known to those skilled in the art and can be designed, for example, to be capable of replicating in prokaryotic and / or eukaryotic cells. Additionally, many vectors can be used directly or in the form of desired fragments isolated therefrom for the transformation of eukaryotic cells and integrated, in whole or in part, into the genome of such cells, thereby generating stable host cells that contain the desired nucleic acid in their genome. The vector used can be any vector suitable for cloning DNA and for transcribing nucleic acids of interest. When using a host cell, it is preferred that the vector is an integrating vector. Alternatively, the vector can be an episomal replication vector.

[0086] Those skilled in the art can select a suitable expression vector and insert the nucleic acid sequence of the present invention in a functional manner. To obtain the expression of a nucleic acid sequence encoding a polypeptide, it is well known to those skilled in the art that a sequence capable of driving expression can be functionally linked to the nucleic acid sequence encoding the polypeptide, thereby generating a recombinant nucleic acid molecule encoding a protein or polypeptide in an expressible form. Generally, the promoter sequence is located upstream of the sequence to be expressed. Many expression vectors are available in the art, such as the pcDNA and pEF vector series from Invitrogen, pMSCV and pTK-Hyg from BD Sciences, pCMV-Script from Stratagene, etc., which can be used to obtain suitable promoter and / or transcription terminator sequences, polyA sequences, etc. In the case of appropriately inserting the sequence encoding the polypeptide of interest with reference to the sequence controlling the transcription and translation of the encoded polypeptide, the resulting expression cassette can be used to produce the polypeptide of interest, which is called expression. The sequence driving expression can include promoters, enhancers, etc., and combinations thereof. These should be able to function in the host cell to drive the expression of the nucleic acid sequence functionally linked to them. Those skilled in the art know that various promoters can be used to obtain the expression of a gene in a host cell. The promoter can be constitutive or regulated and can be obtained from various sources (including viral, prokaryotic or eukaryotic sources) or be artificially designed. The expression of the nucleic acid of interest can be from a native promoter or its derivative or from a completely heterologous promoter (Kaufman, 2000). Some well-known and commonly used promoters for expression in eukaryotic cells include promoters derived from viruses such as adenovirus, such as the E1A promoter; promoters derived from cytomegalovirus (CMV), such as the CMV immediate early (IE) promoter (referred to herein as the CMV promoter) (e.g., available from pcDNA, Invitrogen); promoters derived from simian virus 40 (SV40), etc. Suitable promoters can also be derived from eukaryotic cells, such as the metallothionein (MT) promoter, elongation factor 1α (EF-1α) promoter, ubiquitin C or UB6 promoter, actin promoter, immunoglobulin promoter, heat shock promoter, etc. Testing of promoter function and promoter strength is routine work for those skilled in the art and generally can involve cloning a test gene (such as lacZ, luciferase, GFP, etc.) after the promoter sequence and testing the expression of the test gene. Of course, the promoter can be modified by deletion, addition, mutation of the sequence therein and its functionality can be tested to discover new, attenuated or improved promoter sequences. According to the present invention, a strong promoter that gives a high transcription level in a selected eukaryotic cell is preferred.

[0087] The construct can be transfected into eukaryotic cells (e.g., plant, fungal, yeast, or animal cells) or a suitable prokaryotic expression system (such as E. coli) using methods well-known to those skilled in the art. In some cases, a suitable "tag" sequence (such as, for example but not limited to, his-, myc-, strep-, or flag-tags) or a full protein (such as, for example but not limited to, maltose binding protein or glutathione S-transferase) can be added to the sequences of the present invention to allow purification and / or identification of the polypeptide from the cells or supernatant. Optionally, a sequence containing a specific proteolytic cleavage site can be included to remove the tag by proteolytic digestion later.

[0088] Improved HA trimer stability can be evaluated by size exclusion chromatography. The increased stability is correlated with increased trimer expression levels, lower monomer expression levels, and increased melting temperature. In addition, the long-term stability of the purified trimer can be further tested at elevated temperatures or by assessing the native trimer content after multiple freeze-thaw cycles.

[0089] The purified polypeptide can be analyzed by spectroscopic methods known in the art (e.g., circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and NMR spectroscopy or X-ray crystallography) to study the presence of the desired structures (such as helices and β-sheets). ELISA, Octet, and FACS, etc. can be used to study the binding of the polypeptides of the present invention to previously described broadly neutralizing antibodies (CR8071, CR8033) (19). Thus, polypeptides according to the present invention with the correct conformation can be selected.

[0090] Pharmaceutical / Immunogenic Compositions and Methods of Use

[0091] The present invention further relates to immunogenic compositions comprising a therapeutically effective amount of at least one polypeptide and / or nucleic acid of the present invention. These immunogenic compositions preferably further comprise a pharmaceutically acceptable carrier. In this context, the term "pharmaceutically acceptable" means that the carrier does not cause undue or harmful effects in the subject to which it is administered at the doses and concentrations employed. Such pharmaceutically acceptable carriers and excipients are well known in the art (see Remington's Pharmaceutical Sciences, 18th Edition, A.R. Gennaro, Ed., Mack Publishing Company

[1990] ; Pharmaceutical Formulation Development of Peptides and Proteins, edited by S. Frokjaer and L. Hovgaard, Taylor & Francis

[2000] ; and Handbook of Pharmaceutical Excipients, 3rd Edition, edited by A. Kibbe, Pharmaceutical Press

[2000] ). The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the composition is administered. Aqueous solutions of saline and dextrose, as well as glycerol solutions, can be used, for example, as liquid carriers, especially for injection solutions. The specific formulation should be adapted to the mode of administration. These polypeptide and / or nucleic acid molecules are preferably formulated and administered as sterile solutions. Sterile solutions are prepared by sterile filtration or by other methods known in the art. The solution can then be lyophilized or filled into pharmaceutical dosage containers. The pH of the solution is generally in the range of 3.0 to 9.5, for example, pH 5.0 to pH 7.5.

[0092] The present invention also relates to the influenza mutant hemagglutinin polypeptides, nucleic acid molecules, and / or vectors as described above for inducing an immune response against influenza HA protein. The present invention also relates to a method for inducing an immune response in a subject, the method comprising administering to the subject the polypeptides, nucleic acid molecules, and / or immunogenic compositions as described above. The subject according to the present invention is preferably a mammal capable of being infected by a pathogenic agent of an infectious disease (especially an influenza virus) or otherwise capable of benefiting from the induction of an immune response, such subjects being, for example, rodents (e.g., mice, ferrets), or domestic or farm animals, or non-human primates, or humans. Preferably, the subject is a human subject. Thus, the present invention provides a method for inducing an immune response against influenza B virus hemagglutinin (HA) in a subject using the polypeptides, nucleic acids, and / or immunogenic compositions described herein.

[0093] Since well-known small protein and / or nucleic acid molecules do not always effectively induce an effective immune response, it may be necessary to increase the immunogenicity of the polypeptide and / or nucleic acid molecule by adding an adjuvant. In certain embodiments, the immunogenic compositions described herein comprise an adjuvant or are administered in combination with an adjuvant. The adjuvant for administration in combination with the compositions described herein can be administered before, simultaneously with, or after the administration of the compositions. Examples of suitable adjuvants include aluminum salts such as aluminum hydroxide and / or aluminum phosphate; oil-emulsion compositions (or water-in-oil compositions), including squalene-water emulsions such as MF59 (see, for example, WO 90 / 14837); saponin formulations such as QS21 and immunostimulating complexes (ISCOMs) (see, for example, US 5,057,540; WO 90 / 03184, WO 96 / 11711, WO 2004 / 004762, WO 2005 / 002620); bacterial or microbial derivatives, examples of which are monophosphoryl lipid A (MPL), 3-O-deacylated MPL (3dMPL), oligonucleotides containing CpG motifs, ADP-ribosylated bacterial toxins or mutants thereof such as Escherichia coli heat-labile enterotoxin LT, cholera toxin CT, pertussis toxin PT or tetanus toxoid TT, Matrix M (Isconova). Additionally, known immunopotentiating techniques can be used, such as fusing the polypeptides of the present invention with proteins known in the art to enhance the immune response (e.g., tetanus toxoid, CRM197, rCTB, bacterial flagellin, etc.), or including the polypeptide in virus-like particles, or combinations thereof. Other non-limiting examples that can be used are disclosed, for example, by (20).

[0094] In one embodiment, the influenza mutant hemagglutinin polypeptide of the present invention is incorporated into a virus-like particle (VLP) vector. VLPs generally comprise one or more viral polypeptides that are typically derived from one or more structural proteins of a virus. Preferably, these VLPs are unable to replicate. In certain embodiments, these VLPs may lack the complete genome of the virus or contain a portion of the viral genome. In some embodiments, these VLPs are unable to infect cells. In some embodiments, these VLPs express on their surface one or more viral (e.g., viral surface glycoproteins) or non-viral (e.g., antibodies or proteins) targeting moieties known to those skilled in the art.

[0095] In a particular embodiment, the polypeptide of the present invention is incorporated into virus-like particles. Techniques known to those skilled in the art can be used to produce virus-like particles containing the polypeptide according to the present invention. For example, virus-like particles can be produced by disrupting purified virus, extracting the genome and reassembling the particles with viral proteins (e.g., the mutant influenza hemagglutinin polypeptide described herein) and lipids to form lipid particles containing the viral proteins.

[0096] The present invention also relates to the above-mentioned polypeptides, nucleic acids and / or immunogenic compositions for inducing an immune response against influenza HA in a subject, in particular for use as a vaccine. Thus, the influenza mutant hemagglutinin polypeptides, nucleic acids encoding such polypeptides, or vectors comprising such nucleic acids or polypeptides described herein can be used to elicit protective antibodies against influenza virus. The present invention relates to the polypeptides, nucleic acids and / or immunogenic compositions as described above for use as a vaccine for preventing and / or treating diseases or disorders caused by influenza virus.

[0097] The polypeptides of the present invention can be used after synthesis in vitro or in a suitable cell expression system (including bacteria and eukaryotic cells), or alternatively, can be expressed in a subject in need by expressing a nucleic acid encoding the immunogenic polypeptide. Such nucleic acid vaccines can take any form, including naked DNA, mRNA, self-replicating RNA, circular RNA, plasmid or viral vector (including adenovirus vector).

[0098] Administration of the polypeptides, nucleic acid molecules and / or immunogenic compositions according to the present invention can be carried out using standard routes of administration. Non-limiting examples include parenteral administration (such as intravenous, intradermal, transdermal, intramuscular, subcutaneous, etc.), or mucosal administration (e.g., intranasal, oral, etc.). Those skilled in the art will be able to determine the various possibilities for administering the polypeptides, nucleic acid molecules and / or immunogenic compositions according to the present invention to induce an immune response. In certain embodiments, the polypeptides, nucleic acid molecules and / or immunogenic compositions (or vaccines) are administered more than once, i.e., in a so-called homologous prime-boost regimen. In certain embodiments where the polypeptides, nucleic acid molecules and / or immunogenic compositions are administered more than once, the second dose can be administered, for example, one week or more after the first dose of the polypeptides, nucleic acid molecules and / or immunogenic compositions, two weeks or more after the first dose, three weeks or more after the first dose, one month or more after the first dose, six weeks or more after the first dose, two months or more after the first dose, three months or more after the first dose, four months or more after the first dose, etc. up to an interval of several years after the first dose. The vaccine can also be administered more than twice, such as three times, four times, etc., such that more than one boost administration is carried out after the first prime administration. In other embodiments, the polypeptides, nucleic acid molecules and / or immunogenic compositions according to the present invention are administered only once.

[0099] These polypeptides, nucleic acid molecules and / or immunogenic compositions can also be administered as a prime or as a boost in a heterologous prime-boost regimen.

[0100] The present invention further provides methods for preventing and / or treating influenza virus diseases in a subject using the polypeptides, nucleic acids, and / or compositions described herein. In one particular embodiment, the method for preventing and / or treating influenza virus diseases in a subject comprises administering to a subject in need thereof an effective amount of a polypeptide, nucleic acid, and / or immunogenic composition as described above. A therapeutically effective amount means an amount of the polypeptide, nucleic acid, and / or composition that is effective to prevent, alleviate, and / or treat a disease or disorder caused by infection with an influenza virus, as defined herein. Prevention encompasses inhibiting or reducing the spread of influenza virus or inhibiting or reducing the onset, development, or progression of one or more symptoms associated with influenza virus infection. As used herein, alleviation may refer to reducing the visible or perceivable disease symptoms, viremia, or any other measurable manifestation of influenza infection.

[0101] Those subjects in need of treatment include those who have already developed a condition caused by infection with an influenza virus, as well as those in whom infection with an influenza virus is to be prevented. Thus, the polypeptides, nucleic acids, and / or compositions of the present invention can be administered to naïve subjects, i.e., subjects who do not have a disease caused by influenza virus infection or who have not been infected with influenza virus and are not currently infected with influenza virus, or to subjects who have been infected and / or are currently infected with an influenza virus.

[0102] In one embodiment, the prevention and / or treatment can be directed to groups of patients who are susceptible to influenza virus infection. Such groups of patients include, but are not limited to, for example, the elderly (e.g., ≥50 years old, ≥60 years old, and preferably ≥65 years old), the young (e.g., ≤5 years old, ≤1 year old), hospitalized patients, and patients who have been treated with antiviral compounds but have shown an inadequate antiviral response.

[0103] In another embodiment, the polypeptide, nucleic acid, and / or immunogenic composition can be administered to a subject in combination with one or more other active agents, such as existing or future influenza vaccines, monoclonal antibodies, and / or antiviral agents, and / or antibacterial agents, and / or immunomodulators. The one or more other active agents may be beneficial for treating and / or preventing influenza virus diseases or may alleviate symptoms or disorders associated with influenza virus diseases. In some embodiments, the one or more other active agents are pain relievers, antipyretics, or therapeutic agents that soothe or assist respiration.

[0104] The polypeptides of the present invention can also be used to verify the binding of monoclonal antibodies identified as potential therapeutic candidates. Additionally, the polypeptides of the present invention can be used as diagnostic tools, for example, to test the immune status of an individual by determining the presence of antibodies in the serum of such an individual that are capable of binding to the polypeptides of the present invention. Accordingly, the present invention also relates to an in vitro diagnostic method for detecting the presence of influenza infection in a patient, the method comprising the steps of: a) contacting a biological sample obtained from the patient with a polypeptide according to the present invention; and b) detecting the presence of an antibody-antigen complex.

[0105] The polypeptides of the present invention can also be used to identify new binding molecules or to improve existing binding molecules, such as monoclonal antibodies and antiviral agents.

[0106] The present invention is further illustrated in the following examples and figures. These examples are not intended to limit the scope of the present invention in any way.

[0107] Embodiments

[0108] The present invention also provides the following non-limiting embodiments.

[0109] Embodiment 1 is an isolated mutant influenza hemagglutinin polypeptide, the isolated mutant influenza hemagglutinin polypeptide comprising at least one stabilizing mutation in at least one of the unstable regions (a)-(e) in the polypeptide, wherein the at least one stabilizing mutation comprises a substitution mutation at the following positions:

[0110] (a) Amino acid positions 227, 229 and / or 238; and / or

[0111] (b) Amino acid positions 329 and / or 426; and / or

[0112] (c) Amino acid positions 384, 402, 472 and / or 476; and / or

[0113] (d) Amino acid positions 468, 471, 475 and / or 478; and / or

[0114] (e) Amino acid positions 235, 430 and / or 433;

[0115] wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0116] Embodiment 2 is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, the isolated mutant influenza hemagglutinin polypeptide comprising at least two stabilizing mutations in at least one of the unstable regions (a)-(e) in the polypeptide.

[0117] Embodiment 3 is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, wherein the isolated mutant influenza hemagglutinin polypeptide comprises at least two stabilizing mutations in two, three, four or five of the unstable regions (a)-(e) in the polypeptide.

[0118] Embodiment 3a is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, wherein the isolated mutant influenza hemagglutinin polypeptide comprises at least three stabilizing mutations in three, four or five of the unstable regions (a)-(e) in the polypeptide.

[0119] Embodiment 3b is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, wherein the isolated mutant influenza hemagglutinin polypeptide comprises at least four stabilizing mutations in four or five of the unstable regions (a)-(e) in the polypeptide.

[0120] Embodiment 3c is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, wherein the isolated mutant influenza hemagglutinin polypeptide comprises at least five stabilizing mutations in five of the unstable regions (a)-(e) in the polypeptide.

[0121] Embodiment 4 is the isolated mutant influenza hemagglutinin polypeptide according to Claim 1, wherein the isolated mutant influenza hemagglutinin polypeptide comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen or sixteen stabilizing mutations.

[0122] Embodiment 5 is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 1, wherein

[0123] (a) the amino acid at position 227 is replaced with an amino acid selected from the group consisting of T, L, R, Q, F, I and Y; the amino acid at position 229 is replaced with amino acid L; and / or the amino acid at position 238 is replaced with amino acid F; and / or

[0124] (b) the amino acid at position 329 is replaced with an amino acid selected from the group consisting of M, W and F; and / or the amino acid at position 426 is replaced with an amino acid selected from the group consisting of F, W, Y and P; and / or

[0125] (c) the amino acid at position 384 is replaced with an amino acid selected from F or Y; the amino acid at position 402 is replaced with amino acid A; the amino acid at position 472 is replaced with an amino acid selected from W, R, F, K or L; and / or the amino acid at position 476 is replaced with amino acid F; and / or

[0126] (d) The amino acid at position 468 is replaced by amino acid L; the amino acid at position 471 is replaced by an amino acid selected from V or Q; the amino acid at position 475 is replaced by an amino acid selected from the group consisting of Q, N, W, F, and L; and / or the amino acid at position 478 is replaced by an amino acid selected from W or R; and / or

[0127] (e) The amino acid at position 235 is replaced by amino acid W; the amino acid at position 430 is replaced by an amino acid selected from L or Y; and / or the amino acid at position 433 is replaced by amino acid P.

[0128] Embodiment 6 is the isolated mutant influenza hemagglutinin polypeptide according to Embodiment 5, wherein

[0129] (a) The amino acid at position 384 is replaced by F and the amino acid at position 475 is replaced by W;

[0130] (b) The amino acid at position 384 is replaced by F and the amino acid at position 475 is replaced by Q;

[0131] (c) The amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by K, and the amino acid at position 476 is replaced by F;

[0132] (d) The amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F;

[0133] (e) The amino acid at position 384 is replaced by Y, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F;

[0134] (f) The amino acid at position 476 is replaced by F and the amino acid at position 475 is replaced by W;

[0135] (g) The amino acid at position 476 is replaced by F and the amino acid at position 475 is replaced by Q;

[0136] (h) The amino acid at position 227 is replaced by T and the amino acid at position 426 is replaced by Y;

[0137] (i) The amino acid at position 227 is replaced by T and the amino acid at position 430 is replaced by Y;

[0138] (j) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 430 is replaced by Y;

[0139] (k) The amino acid at position 227 is replaced by T and the amino acid at position 475 is replaced by W;

[0140] (l) The amino acid at position 227 is replaced by T and the amino acid at position 475 is replaced by Q;

[0141] (m) The amino acid at position 227 is replaced by T and the amino acid at position 384 is replaced by F;

[0142] (n) The amino acid at position 227 is replaced by T and the amino acid at position 476 is replaced by F;

[0143] (o) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 475 is replaced by W;

[0144] (p) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 475 is replaced by Q;

[0145] (q) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 475 is replaced by W, and the amino acid at position 430 is replaced by Y;

[0146] (r) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y;

[0147] (s) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 384 is replaced by F;

[0148] (t) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W;

[0149] (u) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by W, and the amino acid at position 430 is replaced by Y;

[0150] (v) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by Q;

[0151] (w) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y;

[0152] (x) The amino acid at position 227 is replaced by T and the amino acid at position 235 is replaced by W;

[0153] (y) The amino acid at position 475 is replaced by W and the amino acid at position 426 is replaced by Y;

[0154] (z) The amino acid at position 475 is replaced by W and the amino acid at position 430 is replaced by Y;

[0155] (aa) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by R;

[0156] (bb) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by F;

[0157] (cc) The amino acid at position 426 is replaced by Y and the amino acid at position 384 is replaced by F;

[0158] (dd) The amino acid at position 426 is replaced by Y and the amino acid at position 476 is replaced by F;

[0159] (ee) The amino acid at position 426 is replaced by Y and the amino acid at position 455 is replaced by A;

[0160] (ff) The amino acid at position 426 is replaced by Y and the amino acid at position 329 is replaced by W;

[0161] (gg) The amino acid at position 430 is replaced by Y and the amino acid at position 384 is replaced by F;

[0162] (hh) The amino acid at position 430 is replaced by Y and the amino acid at position 476 is replaced by F;

[0163] (ii) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by Y;

[0164] (jj) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by W;

[0165] (kk) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by F;

[0166] (ll) The amino acid at position 433 is replaced by P and the amino acid at position 430 is replaced by Y;

[0167] (mm) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by Y;

[0168] (nn) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by W;

[0169] (oo) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by F;

[0170] (pp) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W;

[0171] (qq)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, R is substituted; and at amino acid position 476, F is substituted;

[0172] (rr)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; at amino acid 471, V is substituted; at amino acid position 472, F is substituted; at amino acid position 475, F is substituted; and at amino acid position 478, R is substituted;

[0173] (ss)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; at amino acid 471, V is substituted; at amino acid position 472, W is substituted; at amino acid position 475, F is substituted; and at amino acid position 478, R is substituted;

[0174] (tt)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, W is substituted; and at amino acid position 476, F is substituted;

[0175] (uu)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; at amino acid 471, V is substituted; at amino acid position 472, W is substituted; at amino acid position 475, L is substituted; and at amino acid position 478, R is substituted;

[0176] (vv)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; at amino acid 471, Q is substituted; at amino acid position 472, W is substituted; at amino acid position 475, Q is substituted; and at amino acid position 478, R is substituted;

[0177] (ww)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, K is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted;

[0178] (xx) At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, L is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted;

[0179] (yy) At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 471, Q is substituted; at amino acid position 472, R is substituted; and at amino acid position 476, F is substituted;

[0180] (zz) At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, W is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted;

[0181] (aaa) At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, W is substituted; and at amino acid position 476, F is substituted; or

[0182] (bbb) At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, R is substituted; at amino acid position 475, W is substituted; and at amino acid position 476, F is substituted.

[0183] Embodiment 7 is an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 6, wherein the mutant influenza hemagglutinin polypeptide further comprises an introduced cleavage site.

[0184] Embodiment 8 is an isolated mutant influenza hemagglutinin polypeptide according to Embodiment 7, wherein the introduced cleavage site is a furin cleavage site.

[0185] Embodiment 9 is an isolated mutant influenza hemagglutinin polypeptide according to Embodiment 8, wherein the furin cleavage site is introduced by mutating amino acid positions 359 - 361 of the polypeptide, or wherein the furin cleavage site is introduced by an insertion at the amino terminus of amino acid position 362, wherein the amino acid position corresponds to the amino acid position of SEQ ID NO:1.

[0186] Embodiment 10 is an isolated mutant influenza hemagglutinin polypeptide according to Embodiment 8 or 9, the isolated mutant influenza hemagglutinin polypeptide further comprising an insertion at the carboxyl terminus of the RSV p27 peptide (SEQ ID NO:2) at amino acid position 362.

[0187] Embodiment 11 is an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 9, wherein the amino acid at position 362 is replaced with Q.

[0188] Embodiment 12 is an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 11, the isolated mutant influenza hemagglutinin polypeptide further comprising a deletion of the signal peptide at the amino terminus of the polypeptide.

[0189] Embodiment 13 is an isolated mutant influenza hemagglutinin polypeptide according to Embodiment 12, wherein the signal peptide comprises amino acid positions 1-15 of the polypeptide.

[0190] Embodiment 14 is an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 13, wherein the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46-48, 63, 67-75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204-208, 216, 219-222.

[0191] Embodiment 15 is an isolated mutant influenza hemagglutinin polypeptide according to Embodiment 14, wherein the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46-48, 63, 67-75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204-208, 216, 219-222.

[0192] Embodiment 16 is an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 15, wherein the mutant influenza hemagglutinin polypeptide further comprises a carboxyl (C) terminus truncation starting at amino acid positions from amino acid position 536 to amino acid position 585, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:1.

[0193] Embodiment 17 is an isolated nucleic acid encoding an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 16.

[0194] Embodiment 18 is an isolated vector comprising the isolated nucleic acid according to Embodiment 17.

[0195] Embodiment 19 is an isolated host cell comprising the vector according to Embodiment 18.

[0196] Embodiment 20 is a pharmaceutical composition comprising an isolated mutant influenza hemagglutinin polypeptide according to any one of Embodiments 1 to 16 and a pharmaceutically acceptable carrier.

[0197] Embodiment 21 is a pharmaceutical composition comprising the isolated nucleic acid according to Embodiment 17.

[0198] Embodiment 22 is a pharmaceutical composition comprising the vector according to Embodiment 18.

[0199] Embodiment 23 is a method of inducing an immune response against influenza virus in a subject in need thereof, the method comprising administering to the subject in need thereof a pharmaceutical composition according to any one of Embodiments 20 to 22.

[0200] Embodiment 24 is a method of producing an isolated mutant influenza hemagglutinin polypeptide, the method comprising culturing the isolated host cell according to Embodiment 19 under conditions capable of producing the mutant influenza hemagglutinin polypeptide, and recovering the mutant influenza hemagglutinin polypeptide from the cells or the culture.

[0201] Embodiment 25 is a method of producing the pharmaceutical composition according to Embodiment 20, the method comprising combining the isolated mutant influenza polypeptide with a pharmaceutically acceptable carrier.

[0202] Examples

[0203] Example 1: Localization of Positions of Stabilizing Substitutions in Polypeptide - HA

[0204] For the HA trimer (left) and monomer (right), the altered structures and positions in the polypeptide sequence representing the extracellular domain of influenza virus hemagglutinin (HA0) are shown in Figure 1A as follows. Figure 1BShows the same substitutions in five different unstable regions (head switch, neck switch, stem switch, hinge loop, and repulsion cluster) and three additional regions (fusion peptide, receptor binding site, and base). When expressed as a soluble extracellular domain, the polypeptide is carboxy (C)-terminally truncated; for example, after position 536 of SEQ ID NO:1. Note that for UFV220265 (SEQ ID NO:73), the polypeptide is only 534 amino acids because SEQ ID NO:1 contains two additional amino acids compared to UFV220265( Figure 9 ), omitting the native C-terminal transmembrane and cytoplasmic domains (amino acids 550 - 585)( Figure 2 A). Note that for the numbering of amino acid positions, the wild-type HAB / Brisbane / 60 / 08 (SEQ ID NO:1) numbering is used and includes the signal peptide (residues 1 - 15).

[0205] To stabilize HA, increase expression, and ensure proper folding and trimerization similar to the native conformation of wild-type full-length HA on the surface of virions, amino acid substitutions at the positions shown in Figure 1 were evaluated in the HA polypeptide.

[0206] Example 2: Characterization of Stabilizing Mutations

[0207] Design

[0208] To improve the stability of WT Flu B HA, stabilizing amino acid substitutions were introduced in the following five unstable regions of HA: head switch, neck switch, stem switch, hinge loop, and "repulsion cluster", and three additional regions: fusion peptide, base, and receptor binding site. Most of these regions are pH-sensitive switches (pH switches) and will be unstable if the histidine in the region is protonated at lower pH. The repulsion cluster does not contain histidine but is closely linked to the pH-sensitive stem switch.

[0209] Culture Supernatant Analysis

[0210] Genscript synthesized and codon-optimized plasmids encoding the extracellular domain of wild-type (wt) Flu B Iowa HA protein and variants with amino acid substitutions. In all plasmids, the transmembrane region and cytoplasmic tail were replaced with a 3-residue linker and a C-tag (SEQ ID NO:136). The constructs were cloned into pCDNA2004 by standard methods widely known in the art, including site-directed mutagenesis and PCR, and the constructs were sequenced. The proteins were expressed in Expi293F cells. The Expi293F cells were transiently transfected using ExpiFectamine (Life Technologies; Carlsbad, CA) according to the manufacturer's instructions and cultured at 37 °C and 10% CO2 for 3 days. The culture supernatant was collected and the cells and cell debris were removed by centrifugation at 300 g for 5 minutes. Subsequently, the clarified supernatant was sterile filtered using a 0.22 μm vacuum filter and stored at 4 °C until use. Analytical SEC on the day of harvest ( Figure 2 ) was performed on a Vanquish ultra-high performance liquid chromatography system (Thermo Fisher Scientific; Waltham, MA) and a μDAWN light scattering detector (Wyatt) coupled to an Optilab μT-rEX refractive index detector (Wyatt Technology Corporation; Santa Barbara, CA) in combination with an online Nanostar DLS reader (Wyatt Technology Corporation). The clarified crude cell culture supernatant was applied at 0.3 mL / min to a UnixC SEC-300 15 cm column (Sepax catalog number 231300-4615) with a corresponding guard column (Sepax) equilibrated in running buffer (150 mM sodium phosphate, 50 mM NaCl, pH 7.0). When analyzing supernatant samples, the μMALS detector was offline and the analytical SEC data was analyzed using the Chromeleon software package. The stability of different proteins in the supernatant was also determined by measuring the melting temperature (Tm) using differential scanning fluorimetry (DSF) ( Figure 3and Table 2). To this end, SYPRO Orange 5000x (S6650, Invitrogen; Waltham, MA) was diluted in PBS (1:250) to obtain a 20x working solution. For each reaction, 15 μL of the supernatant was mixed with 5 μL of SYPRO 20x in a MicroAmp Fast Optical 96-well plate (4346906, Thermo Fisher Scientific). PBS was used as a negative control. The plate was covered with a MicroAmp Optical Adhesive Film (4311971, Thermo Fisher Scientific) and subsequently read in a ViiA7 real-time PCR machine. The melting temperature of all HA variants was expressed as the temperature at which 50% of the protein was melted (Tm 50 )(Table 2).

[0211] Results and Conclusions

[0212] Comparison of trimer expression levels and monomer content by analytical size exclusion chromatography (SEC) of clarified cell culture supernatants of wt Flu B HA and HA variants with stabilizing substitutions was shown in Figure 2 and stability based on melting temperature (Tm 50 ) was shown in Table 2 and Figure 3 .

[0213] Table 2. Trimer expression and temperature stability of polypeptide variants. Peak area (size exclusion chromatography) and Tm 50 values (differential scanning fluorimetry)

[0214]

[0215]

[0216]

[0217] Polypeptides with improved temperature stability (Tm 50 increase > 0.5 °C) and / or improved trimer % (≥ 5%) compared to reference (UFV212130) are indicated with *. ◆ Values obtained in different experiments, where reference polypeptide UFV212130 showed values similar to those listed here.

[0218] The relative stabilizing potential of different amino acid substitutions was shown in the scatter plot in Figure 3 which shows the expression level of the trimer (trimer peak area under the curve) versus the percentage of the trimer. The diameter of the marker was scaled based on the Tm 50 listed in Table 2. All three values are related to the mass and stability of the HA trimer.

[0219] Stable amino acid substitutions were found in all 5 regions:

[0220] - Head switch (K227L, K227T, K227R, K227Q, K227F, K227I, K227Y, T229L, T277V, T236N, H238F, and H235T)

[0221] - Neck switch (Q426F, Q426W, Q426Y, and S455A)

[0222] - Stem switch (H384F, H384Y, H384W, H476Y, H476F, and S472R)

[0223] - Repulsion cluster (E475Q, E475N, E475W, E475F, E475L, L478W, and L478R)

[0224] - Hinge loop (V235K, V235W, G430L, G430Y, and D433P)

[0225] SEC analysis of the culture supernatants of Expi293F cells expressing polypeptides comprising these substitutions showed an increase in trimer expression titer and trimer % compared to wild-type HA. Additionally, DSF analysis indicated that the improved expression correlated with an increase in the melting temperature, suggesting that all three values are related to the quality and stability of the HA trimer.

[0226] Example 3: Characterization of Combinations of Stabilizing Mutations

[0227] Design

[0228] Next, variants with combinations of the selected mutations were constructed to evaluate whether their effects on trimer expression, trimer ratio, and melting temperature were additive. The stable amino acid substitutions selected from each region were combined and compared to single-strand mutations taken from Figure 3 of.

[0229] Culture Supernatant Analysis

[0230] DNA fragments encoding the polypeptides were synthesized and the polypeptides were produced in Expi293F cells as described in Example 2. As described in Example 2, peak areas (trimer and trimer %) and temperature stability values were obtained by SEC and DSF.

[0231] Results and Conclusions

[0232] Figures 4A - 4E SEC profiles of the clarified cell culture supernatants of Expi293F cells expressing the polypeptides are shown. The compilation of all data for the mutation combination data is listed in Table 3 and is shown inFigure 5 is shown in the scatter plot therein, which shows the expression level of the trimer and the percentage of the trimer. Based on the Tm listed in Table 3 50 Scale the diameter of the marker.

[0233] Table 3. Trimer Expression and Thermal Stability of Polypeptide Variants. Peak Area of the Polypeptides of the Invention in Culture Harvest (Size-exclusion chromatography) and Tm 50 value (Differential scanning fluorimetry)

[0234]

[0235]

[0236]

[0237] *Polypeptides with improved thermal stability (Tm 50 increase > 0.5 °C) compared to single mutants. ◆ Values obtained in different experiments, where the reference polypeptide UFV212130 showed values similar to those listed here.

[0238] Compared to the WT HA reference polypeptide (UFV212130), most variants with combinations of the selected mutations showed an expression titer of approximately 2 - 3 times, and a higher trimer %, except for the combination E475F + L478W (UFV220313). The improved expression was independent of the type of combination (within a single region or within multiple regions), and was closely related to the observed increase in the melting temperature compared to single mutant polypeptides. The top three expressing polypeptides contained 4 substitutions in the stem switch; UFV220455 (substitutions H384F, S402A, S472W, and H476F), UFV220521 (substitutions H384Y, S402A, S472R, H476F), and UFV220522 (substitutions H384Y, S402A, S472W, and H476F). For these variants, the relative trimer percentages were 93.6%, 95.6%, and 92.8%, respectively. However, compared to these three variants, polypeptides with substitutions in two regions showed a lower expression titer and improved trimer %. Combinations of substitutions from multiple regions improved the expression level and trimer % (up to 100%), as well as the protein thermal stability. The polypeptide UFV220265 containing substitutions in all 5 unstable regions showed the highest expression level (9.7 mAU*mL) and the highest thermal stability (Tm 50 was 71.5 °C). In summary, substitutions in different regions are additive and improve trimer titer and protein stability.

[0239] Example 4: Universal Single - Chain

[0240] Design

[0241] Next, the generality of the stabilizing substitutions was tested by introducing stabilizing substitutions into soluble HAs from both the Yamagata (B / Singapore / INFTT-16-0610 / 2016 and B / Florida / 04 / 2006) and Victoria lineages (B / Iowa / 06 / 2017, B / Brisbane / 60 / 08, and B / Ohio / 01 / 05). Some of the sequences obtained from the GISAID initiative and / or the Influenza Virus Database contained extremely rare strain-specific residues. These rare residues may have been acquired, for example, through chicken embryo adaptation, sequencing errors, or other reasons, and needed to be optimized or "fixed" in order to obtain a native sequence that could fold correctly and efficiently (9, 21). For two non-expressing HAs, several very rare residues were substituted with consensus Flu B HAs (Table 4). Figure 6A It was shown that two HA sequences (B / Victoria / 02 / 1987; SEQ ID NO: 224 and 225 and B / Guangdong / 120 / 2000; SEQ ID NO: 226 and 227) repaired according to the substitutions listed in Table 4 showed high expression of HA in analytical SEC. Next, for three other HAs (B / Ohio / 01 / 2005, B / Florida / 04 / 2006, and B / Singapore / INFTT-16-0610 / 2016), two very rare mutations were observed, and thus these mutations were "repaired" back to consensus residues (Table 4).

[0242] Table 4. Repair Mutations of HA Polypeptides. Reverse Mutations of Rare Amino Acids and Frequencies Compared to Consensus Sequences Before and After and Frequencies.

[0243]

[0244]

[0245] HA was stabilized at different levels by selecting different stabilizing substitutions. A fully stabilized version was designed by introducing five stabilizing substitutions (K227T + H384F + Q426Y + G430Y + E475W) from five different unstable regions. A less stable version was prepared by introducing two pH-switch regions (K227T in the head switch and H384F in the stem switch) and three stabilizing substitutions in the repulsive cluster region (E475W) or two stabilizing substitutions from the neck switch region (H329W, Q426W).

[0246] Culture Supernatant Analysis

[0247] For wild-type and stabilized HA, clarified cell culture supernatants of Expi293F cells expressing the polypeptide were obtained as described in Example 2. As described in Example 2, relative trimer expression and the percentage of trimers were calculated by integrating the peak areas of the trimer and monomer in SEC. The temperature stability was obtained by measuring the melting temperature by DSF as described in Example 2.

[0248] Results and Conclusions

[0249] Figure 6A It was shown that in order to demonstrate the general nature of the stable substitutions, it was important to ensure that HA showed any expression. Thus, in Figure 6A it was shown that HA expression was obtained by substituting very rare mutations with consensus residues even without introducing any stable substitutions. Apparently, some HAs contained sequencing errors or, for example, chicken embryo adaptation, and HA expression was detected only when the incorrect mutations were reverted to wild-type. Thus, B / Victoria / 02 / 1987 and B / Guangdong / 120 / 2000 were repaired according to Table 4 to ensure that stable substitutions had an impact on well-folded HA in the absence of inherent sequence errors. Figure 6B SEC chromatograms of clarified cell culture supernatants of Expi293F cells expressing the polypeptide are shown. The peak areas (total trimer expression and trimer %) and temperature stability values are listed in Table 5.

[0250] Table 5. Trimer Expression and Thermal Stability of Polypeptide Variants. Peak Area of the Polypeptides of the Invention in Culture Harvest (Size-exclusion chromatography) and Tm 50 value (Differential scanning fluorimetry)

[0251]

[0252]

[0253] ◆ Include 2 back-to-consensus repair mutations * The stabilized polypeptides contain mutations; A. K227T, H384F, Q426Y, G430Y and E475W, B. K227T, H384F and E475W, C. H329W and Q426W.

[0254] Compared to the WT HA polypeptide, all stable variants showed higher expression titers, increased trimer % and improved thermal stability. However, for stable variant C (only the stable neck switch region), variant B (stable head and stalk pH switches + repulsive clusters) and A (stable in all 5 regions), some monomeric polypeptides were observed to be expressed only as trimeric polypeptides. Variant A polypeptides, which are stable in all 5 regions, showed a melting temperature approximately 3°C - 6°C higher than variant B polypeptides without the Q426Y and G430Y mutations, indicating the importance of these two substitutions. Collectively, these findings suggest that the stabilizing mutations are generally applicable to HA from both the Yamagata and Victoria lineages.

[0255] Example 5: Characterization of Stabilizing Mutations in Cleaved HA

[0256] Design

[0257] HA requires proteolytic cleavage to undergo maturation. The cleaved HA folds into a native trimeric conformation, where the fusion peptide participates in the trimerization reaction (22, 23, and 24). The maturation step can increase the stability of HA at neutral pH, but it decreases the stability at low pH, as low pH triggers the conformational changes required for membrane fusion. In known mammalian cell expression systems, HA cleavage does not occur during expression. Therefore, a cleavable variant of the polypeptide was designed that can be post-translationally cleaved in mammalian cells by inserting a 27-residue peptide derived from respiratory syncytial virus at the HA0 cleavage site ( Figure 1K ). If inserted between the furin cleavage site or weak furin cleavage site and the fusion peptide, the furin-like protease present in mammalian cells cleaves out the P27 peptide from the respiratory syncytial virus fusion protein ( Figure 1K ). Since furin operates at low pH, this furin-based maturation step can only succeed if HA is sufficiently stabilized to maintain its pre-fusion conformation. As in Example 4, 3 variants with different stability levels were tested for each strain; fully stable (variant A) and less stable (variants B and C), and all constructs contained the cleavable p27 peptide.

[0258] Culture Supernatant Analysis

[0259] The HA variant described in Example 4 was modified by inserting RSV p27 prior to the fusion peptide, and the plasmid was transfected into Expi293F cells as described in Example 2, except that now 20% of the vector encoding furin was co-transfected to ensure sufficient intracellular furin levels for the design including the P27 peptide. As described in Example 2, the peak areas (trimer and trimer %) and temperature stability values obtained by SEC and DSF were obtained. Additionally, the culture supernatant was analyzed by Western blot to analyze the processing of HA0 into HA1 and HA2. Briefly, 10 μL of clarified supernatant was mixed with lithium dodecyl sulfate (LDS) sample buffer to prepare a protein sample for denaturing gel electrophoresis and incubated at 95 °C for 10 minutes under reducing conditions. The samples were run at 200 V for 30 minutes on a 4%-12% Bolt Bis-Tris Gel (Invitrogen). After that, the semi-wet rinsed gel was blotted onto a PVDF membrane using iBlot 2 (Invitrogen). Then, the membrane was blocked in Intercept blocking buffer (Li-Cor) for 60 minutes, washed with TBS-T (3 × 5 minutes), incubated with streptavidin CW800 (Li-Cor) for 45 minutes, washed with TBS-T (2 × 5 minutes), and subsequently washed finally with PBS. The C-labeled polypeptide was visualized by scanning on an Odyssey scanner (Li-Cor Biosciences; Lincoln, NE).

[0260] Results and Conclusions

[0261] Figures 6C - 6D SEC chromatograms and WB of the clarified cell culture supernatant of Expi293F cells expressing the polypeptide are shown. The peak areas (total trimer expression and trimer %) and temperature stability values are listed in Table 6.

[0262] Table 6. Trimer Expression and Thermal Stability of HA Variants. Peak Area of the Polypeptides of the Invention in Culture Harvest (Size-exclusion chromatography) and Tm 50 value (Differential scanning fluorimetry)

[0263]

[0264]

[0265] 1. All HAs are cleavable and include the P27 peptide, 2. The stable polypeptides contain mutations; A. K227T, H384F, Q426Y, G430Y, and E475W, B. K227T, H384F, and E475W, C. H329W and Q426W.

[0266] Only A variants containing HA with 5 stabilizing substitutions in all 5 labile regions showed high trimer expression, while for labile or semi-stable HA, only low levels of monomer were observed in SEC ( Figure 6B ). The melting temperature of the fully stabilized variant after cleavage was similar to that of the uncleaved variant (Table 5). On a reduced Western blot, a band corresponding to HA2 was observed in the culture supernatant of Exi293F cells co-transfected with furin and expressing the fully stabilized cleavable variant, indicating processing of the introduced furin site ( Figure 6C ). In summary, cleavable trimers and temperature-stable HA polypeptides were produced; however, full stabilization (K227T, H384F, Q426Y, G430Y, and E475W) was required for cleavage at low pH.

[0267] Example 6

[0268] Design

[0269] As described in Example 5, additional combinations of stabilizing substitutions in the stem-switch region and the repulsive 3-fold axis cluster were tested in furin-cleavable Flu B HA (B / Iowa / 06 / 2017). Alternative stabilizing substitutions in the stem-switch and repulsive clusters were evaluated in a furin-cleavable HA parental design containing 3 substitutions: K227T, Q426Y, and G430Y (Table 7).

[0270] Culture Supernatant Analysis

[0271] As described in Example 5, plasmids encoding cleavable polypeptides were transfected into Expi293F cells. Peak areas (trimer and trimer %) and temperature stability values were obtained by SEC and DSF as described in Example 2.

[0272] Results and Conclusions

[0273] Figure 7 SEC profiles of clarified cell culture supernatants of Expi293F cells expressing polypeptides are shown. Peak areas (total trimer expression and trimer %) and temperature stability values are listed in Table 7 and shown in the Figure 8 scatter plot, which shows the trimer expression level and percentage of trimer for polypeptides showing a significant trimer peak (>2 mAu*mL) in SEC. The markers were scaled based on the Tm 50 values listed in Table 7.

[0274] Table 7. Trimer Expression and Thermal Stability of Polypeptide Variants. Peak Area of the Polypeptides of the Invention in Culture Harvest (Size exclusion chromatography) and Tm 50 value (Differential scanning fluorimetry)

[0275]

[0276]

[0277] *All except UFV212130 include K227T, Q426Y, and G430Y mutations. ◆ The values of low-expressed proteins (peak height of OD280 < 10 mAu in the SEC graph) are not shown (listed as n.a.).

[0278] For variants without the stable substitution of H384F (UFV221167 and UFV221171), no trimers and monomers or extremely low levels of trimers and monomers were observed in SEC ( Figure 7 ), while variants containing this substitution were all expressed only as trimers (Table 7). The polypeptide UFV221176 was shown to be the most temperature-stable variant, and the polypeptide UFV221162 was expressed at the highest level. The second (UFV221175) and third (UFV221174) most stable polypeptides differed in the substitution at position 472, being L and K respectively, while in the most stable polypeptide, this position was mutated to arginine. For these polypeptides, stability was related to the expression level; UFV221176, UFV221175, and UFV221174 were 7.5, 6.2, and 5.4 respectively. In summary, additional substitutions at positions 402, 472, 475, and 476 further improved the expression titer, trimer %, and protein stability.

[0279] References

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[0311] Sequences

[0312] SEQ ID NO 1: Full - length B / Brisbane / 60 / 08

[0313] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITAASLNDDGLDNHTILLYYSTAASSLAVTLMIAIFVVYMVSRDNVSCSICL

[0314] SEQ ID NO 2: RSV p27 Peptide

[0315] ELPRFMNYTLNNAKKTNVTLSKKRKRR

[0316] SEQ ID NO 3 UFV212130 Soluble (Extracellular Domain) B / IOWA / 06 / 2017

[0317] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0318] SEQ ID NO 4: UFV212175

[0319] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGWFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0320] SEQ ID NO 5: UFV212136

[0321] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQLFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0322] SEQ ID NO 6: UFV212137

[0323] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0324] SEQ ID NO 7: UFV212138

[0325] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQRFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0326] SEQ ID NO 8: UFV212199

[0327] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFVSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0328] SEQ ID NO 9: UFV212200

[0329] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFLSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0330] SEQ ID NO 10: UFV212173

[0331] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSAANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0332] SEQ ID NO 11: UFV212208

[0333] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGKTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0334] SEQ ID NO 12: UFV212209

[0335] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGWTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0336] SEQ ID NO 13: UFV212139

[0337] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVVTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0338] SEQ ID NO 14: UFV212140

[0339] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0340] SEQ ID NO 15: UFV212174

[0341] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVITHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0342] SEQ ID NO16: UFV212141

[0343] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTTYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0344] SEQ ID NO 17: UFV212201

[0345] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTIVYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0346] SEQ ID NO 18: UFV212170

[0347] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEMAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0348] SEQ ID NO 19: UFV212171

[0349] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0350] SEQ ID NO 20: UFV212172

[0351] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEFAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0352] SEQ ID NO 21: UFV212196

[0353] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKMIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0354] SEQ ID NO 22: UFV212216

[0355] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLPGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0356] SEQ ID NO 23: UFV212215

[0357] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWPGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0358] SEQ ID NO 24: UFV212212

[0359] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMPAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0360] SEQ ID NO 25: UFV212143

[0361] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0362] SEQ ID NO 26: UFV212188

[0363] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWYGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0364] SEQ ID NO 27: UFV212217

[0365] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGPHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0366] SEQ ID NO 28: UFV212203

[0367] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAWGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0368] SEQ ID NO 29: UFV212155

[0369] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLFRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0370] SEQ ID NO 30: UFV212156

[0371] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0372] SEQ ID NO 31: UFV212157

[0373] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0374] SEQ ID NO 32: UFV212211

[0375] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLPRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0376] SEQ ID NO 33: UFV212144

[0377] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLAGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0378] SEQ ID NO 34: UFV212145

[0379] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLTGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0380] SEQ ID NO 35: UFV212163

[0381] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSLAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0382] SEQ ID NO 36: UFV212164

[0383] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0384] SEQ ID NO 37: UFV212166

[0385] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0386] SEQ ID NO 38: UFV212193

[0387] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADVISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0388] SEQ ID NO 39: UFV212194

[0389] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADIISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0390] SEQ ID NO 40: UFV212165

[0391] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0392] SEQ ID NO 41: UFV212202

[0393] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0394] SEQ ID NO 42: UFV212161

[0395] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSQDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0396] SEQ ID NO 43: UFV212162

[0397] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSLDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0398] SEQ ID NO 44: UFV212148

[0399] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0400] SEQ ID NO 45: UFV212149

[0401] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDNHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0402] SEQ ID NO 46: UFV212150

[0403] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0404] SEQ ID NO 47: UFV212151

[0405] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDFHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0406] SEQ ID NO 48: UFV212152

[0407] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDLHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0408] SEQ ID NO 49: UFV212153

[0409] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0410] SEQ ID NO 50: UFV212181

[0411] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLWALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0412] SEQ ID NO 51: UFV212182

[0413] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0414] SEQ ID NO 52: UFV220244

[0415] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0416] SEQ ID NO 53: UFV220245

[0417] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0418] SEQ ID NO 54: UFV220246

[0419] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0420] SEQ ID NO 55: UFV220247

[0421] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0422] SEQ ID NO 56: UFV220248

[0423] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0424] SEQ ID NO 57: UFV220249

[0425] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0426] SEQ ID NO 58: UFV220250

[0427] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0428] SEQ ID NO 59: UFV220251

[0429] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWFLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0430] SEQ ID NO 60: UFV220252

[0431] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0432] SEQ ID NO 61: UFV220253

[0433] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0434] SEQ ID NO 62: UFV220254

[0435] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0436] SEQ ID NO 63: UFV220255

[0437] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0438] SEQ ID NO 64: UFV220256

[0439] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0440] SEQ ID NO 65: UFV220257

[0441] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0442] SEQ ID NO 66: UFV220258

[0443] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0444] SEQ ID NO 67: UFV220259

[0445] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0446] SEQ ID NO68: UFV220260

[0447] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0448] SE Q ID NO69: UFV220261

[0449] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0450] SE Q ID NO70: UFV220262

[0451] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0452] SEQ ID NO71: UFV220263

[0453] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0454] SE Q ID NO72: UFV220264

[0455] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0456] SE Q ID NO73: UFV220265

[0457] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0458] SE Q ID NO74: UFV220266

[0459] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0460] SE Q ID NO75: UFV220267

[0461] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0462] SE Q ID NO76: UFV220268

[0463] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0464] SE Q ID NO77: UFV220269

[0465] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0466] SE Q ID NO78: UFV220270

[0467] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0468] SE Q ID NO79: UFV220271

[0469] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0470] SE Q ID NO80: UFV220272

[0471] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0472] SE Q ID NO81: UFV220273

[0473] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0474] SE Q ID NO82: UFV220274

[0475] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0476] SE Q ID NO83: UFV220275

[0477] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0478] SE Q ID NO84: UFV220276

[0479] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFLSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0480] SE Q ID NO85: UFV220277

[0481] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQLFLSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0482] SE Q ID NO86: UFV220278

[0483] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFLSSANGWTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0484] SE Q ID NO87: UFV220279

[0485] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFLSSANGKTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0486] SE Q ID NO88: UFV220280

[0487] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFLSSANGVNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0488] SE Q ID NO89: UFV220281

[0489] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGWTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0490] SE Q ID NO90: UFV220282

[0491] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGKTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0492] SE Q ID NO91: UFV220283

[0493] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0494] SE Q ID NO92: UFV220284

[0495] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQLFTSSANGWTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0496] SE Q ID NO93: UFV220285

[0497] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQLFTSSANGKTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0498] SE Q ID NO94: UFV220286

[0499] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQLFTSSANGVNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0500] SE Q ID NO95: UFV220287

[0501] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGWNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0502] SE Q ID NO96: UFV220288

[0503] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGKNTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0504] SE Q ID NO97: UFV220289

[0505] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0506] SE Q ID NO98: UFV220290

[0507] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0508] SE Q ID NO99: UFV220291

[0509] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0510] SE Q ID NO100: UFV220292

[0511] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLFRLSGAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0512] SE Q ID NO101: UFV220293

[0513] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMPELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0514] SE Q ID NO102: UFV220294

[0515] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMPELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0516] SE Q ID NO103: UFV220295

[0517] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0518] SE Q ID NO104: UFV220296

[0519] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0520] SE Q ID NO105: UFV220297

[0521] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLFRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0522] SE Q ID NO106: UFV220298

[0523] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0524] SE Q ID NO107: UFV220299

[0525] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0526] SE Q ID NO108: UFV220300

[0527] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0528] SE Q ID NO109: UFV220301

[0529] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0530] SE Q ID NO110: UFV220302

[0531] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0532] SE Q ID NO111: UFV220303

[0533] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0534] SE Q ID NO112: UFV220304

[0535] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLFRLSGAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0536] SE Q ID NO113: UFV220305

[0537] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLFRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0538] SE Q ID NO114: UFV220306

[0539] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTIASQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0540] SE Q ID NO115: UFV220307

[0541] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLWALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0542] SE Q ID NO116: UFV220308

[0543] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLFALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0544] SE Q ID NO117: UFV220309

[0545] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0546] SE Q ID NO118: UFV220310

[0547] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDLHLWALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0548] SE Q ID NO119: UFV220311

[0549] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDLHLFALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0550] SE Q ID NO120: UFV220312

[0551] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDLHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0552] SE Q ID NO121: UFV220313

[0553] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDFHLWALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0554] SE Q ID NO122: UFV220314

[0555] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDFHLFALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0556] SE Q ID NO123: UFV220315

[0557] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDFHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0558] SE Q ID NO124: UFV220316

[0559] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLWALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0560] SE Q ID NO125: UFV220317

[0561] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLFALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0562] SE Q ID NO126: UFV220318

[0563] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDQHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0564] SEQ ID NO127: UFV220319

[0565] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0566] SE Q ID NO128: UFV220320

[0567] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWYGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0568] SE Q ID NO129: UFV220450

[0569] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINKEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0570] SE Q ID NO130: UFV220454

[0571] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0572] SE Q ID NO131: UFV220455

[0573] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0574] SE Q ID NO132: UFV220521

[0575] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWYGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0576] SE Q ID NO133: UFV220522

[0577] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWYGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0578] SEQ ID NO NO134: HIS-tag

[0579] HHHHHH

[0580] SEQ ID NO NO135: HIS-tag

[0581] HHHHHHH

[0582] SE Q ID NO136: C-tag

[0583] EPEA

[0584] SEQ ID NO NO137: FLAG tag

[0585] DYKDDDDK

[0586] SE Q ID NO NO138: Factor X protease cleavage site

[0587] IEGR

[0588] SE Q ID NO139: Thrombin protease cleavage site

[0589] LVPRGS

[0590] SEQ ID NO NO140: UFV220877

[0591] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0592] SE Q ID NO141: UFV220880 soluble (extracellular domain) B / Ohio / 01 / 2005

[0593] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0594] SE Q ID NO142: UFV220882

[0595] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0596] SE Q ID NO143: UFV220884

[0597] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0598] SE Q ID NO144: UFV220886

[0599] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0600] SEQ ID NO NO145: UFV220888 soluble (extracellular domain) B / Brisbane / 60 / 2008

[0601] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0602] SE Q ID NO146: UFV220890

[0603] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0604] SE Q ID NO147: UFV220892

[0605] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0606] SE Q ID NO148: UFV220894

[0607] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0608] SE Q ID NO149: UFV220896 soluble (extracellular domain) B / Florida / 04 / 2006

[0609] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0610] SE Q ID NO150: UFV220898

[0611] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQTFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0612] SE Q ID NO151: UFV220900

[0613] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQTFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0614] SE Q ID NO152: UFV220902

[0615] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0616] SE Q ID NO153: UFV220904 soluble (extracellular domain) B / Singapore / INFTT-16-0610 / 2016

[0617] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0618] SEQ ID NO NO154: UFV220906

[0619] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQTFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0620] SE Q ID NO155: UFV220908

[0621] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQTFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0622] SE Q ID NO156: UFV220910

[0623] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0624] SE Q ID NO157: UFV220875

[0625] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0626] SEQ ID NO NO158: UFV220876

[0627] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0628] SE Q ID NO159: UFV220878

[0629] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0630] SEQ ID NO NO160: UFV220879

[0631] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0632] SEQ ID NO NO161: UFV220881

[0633] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0634] SE Q ID NO162: UFV220883

[0635] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0636] SEQ ID NO NO163: UFV220885

[0637] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0638] SE Q ID NO164: UFV220887

[0639] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTKTRGKLCPKCLNCTDLDVALGRPKCTGNIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAEKAPGGPYKIGTSGSCPNVTNGNGFFATMAWAVPKNDNNKTATNSLTIEVPYICTEGEDQITIWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0640] SE Q ID NO165: UFV220889

[0641] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0642] SE Q ID NO166: UFV220891

[0643] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0644] SE Q ID NO167: UFV220893

[0645] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0646] SE Q ID NO168: UFV220895

[0647] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHIRLSTHNVINAENAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPKNDKNKTATNPLTIEVPYICTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFDAGEFSLPTFDSLNITA

[0648] SEQ ID NO NO169: UFV220897

[0649] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0650] SE Q ID NO170: UFV220899

[0651] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQTFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0652] SEQ ID NO NO171: UFV220901

[0653] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQTFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0654] SEQ ID NO NO172: UFV220903

[0655] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYENIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKSGFFATMAWAVPKDNNKNATNPLTVEVPYICTEGEDQITVWGFHSDDKTQMKNLYGDSNPQKFTSSANGVTTHYVSQIGGFPDQTEDGGLPQSGRIVVDYMMQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0656] SE Q ID NO173: UFV220905

[0657] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0658] SEQ ID NO NO174: UFV220907

[0659] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQTFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0660] SE Q ID NO175: UFV220909

[0661] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQTFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDWHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0662] SE Q ID NO176: UFV220911

[0663] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSYFANLKGTRTRGKLCPDCLNCTDLDVALGRPMCVGTTPSAKASILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEKIRLSTQNVIDAEKAPGGPYRLGTSGSCPNATSKIGFFATMAWAVPKDNYKNATNPQTVEVPYICTEGEDQITVWGFHSDNKTQMKSLYGDSNPQKFTSSANGVTTHYVSQIGDFPDQTEDGGLPQSGRIVVDYMVQKPGKTGTIVYQRGVLLPQKVWCASGRSKVIKGSLPLIGEADCLHEEYGGLNKSKPYYTGKWAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLWRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVDIGNGCFETKHKCNQTCLDRIAAGTFNAGEFSLPTFDSLNITA

[0664] SE Q ID NO:177

[0665] ELPRFMNYTLNNAKKTNVTLSKKRKRR

[0666] SE Q ID NO178: UFV221029

[0667] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQQFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0668] SE Q ID NO179: UFV221030

[0669] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQNFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0670] SEQ ID NO 180: UFV221031

[0671] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQFFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0672] SE Q ID NO181: UFV221032

[0673] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQIFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0674] SE Q ID NO182: UFV221033

[0675] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQYFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0676] SE Q ID NO183: UFV221034

[0677] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTNYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0678] SE Q ID NO184: UFV221035

[0679] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTQYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0680] SE Q ID NO185: UFV221036

[0681] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTIYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0682] SE Q ID NO186: UFV221037

[0683] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTFYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0684] SE Q ID NO187: UFV221038

[0685] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWWGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0686] SE Q ID NO188: UFV221039

[0687] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWNGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0688] SE Q ID NO189: UFV221040

[0689] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWQGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0690] SE Q ID NO190: UFV221041

[0691] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWIGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0692] SE Q ID NO191: UFV221184

[0693] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0694] SE Q ID NO192: UFV221185

[0695] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINKEDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0696] SE Q ID NO193: UFV221186

[0697] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDEHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0698] SE Q ID NO194: UFV221042

[0699] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEWLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0700] SE Q ID NO195: UFV221043

[0701] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEYLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0702] SE Q ID NO196: UFV221044

[0703] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEILLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0704] SE Q ID NO197: UFV221045

[0705] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDENLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0706] SE Q ID NO198: UFV221046

[0707] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQKFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLQRLSGAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINSEDEQLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0708] SE Q ID NO199: UFV221159

[0709] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINKEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0710] SE Q ID NO200: UFV221160

[0711] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINLEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0712] SEQ ID NO 201: UFV221161

[0713] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0714] SE Q ID NO202: UFV221162

[0715] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0716] SE Q ID NO203: UFV221163

[0717] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDFHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0718] SEQ ID NO 204: UFV221164

[0719] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVFEDFHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0720] SE Q ID NO205: UFV221165

[0721] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDFHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0722] SEQ ID NO 206: UFV221166

[0723] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDEFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0724] SEQ ID NO 207: UFV221167

[0725] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDLHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0726] SE Q ID NO208: UFV221168

[0727] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIQWEDQHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0728] SEQ ID NO 209: UFV221169

[0729] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDQHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0730] SE Q ID NO210: UFV221170

[0731] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDRHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0732] SE Q ID NO211: UFV221171

[0733] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIIWEDWHLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0734] SEQ ID NO 212: UFV221172

[0735] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVFEDWHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0736] SE Q ID NO213: UFV221173

[0737] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWHGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNELIIVWEDWHLRALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0738] SE Q ID NO214: UFV221174

[0739] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINKEDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0740] SEQ ID NO 215: UFV221175

[0741] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINLEDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0742] SE Q ID NO216: UFV221176

[0743] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0744] SEQ ID NO 217: UFV221177

[0745] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0746] SEQ ID NO 218: UFV221178

[0747] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDWFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0748] SE Q ID NO219: UFV221179

[0749] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINKEDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0750] SEQ ID NO 220: UFV221180

[0751] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINLEDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0752] SE Q ID NO221: UFV221181

[0753] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINREDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0754] SE Q ID NO222: UFV221182

[0755] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKATQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

[0756] SEQ ID NO 223: UFV221183

[0757] MKAIIVLLMVVTSNADRICTGITSSNSPHVVKTATQGEVNVTGVIPLTTTPTKSHFANLKGTETRGKLCPKCLNCTDLDVALGRPKCTGKIPSARVSILHEVRPVTSGCFPIMHDRTKIRQLPNLLRGYEHVRLSTHNVINAEGAPGGPYKIGTSGSCPNITNGNGFFATMAWAVPDKNKTATNPLTIEVPYVCTEGEDQITVWGFHSDNETQMAKLYGDSKPQTFTSSANGVTTHYVSQIGGFPNQTEDGGLPQSGRIVVDYMVQKSGKTGTITYQRGILLPQKVWCASGRSKVIKGSLPLIGEADCLHEKYGGLNKSKPYYTGEHAKAIGNCPIWVKTPLKLANGTKYRPPAKLLKERELPRFMNYTLNNAKKTNVTLSKKRKRRGFFGAIAGFLEGGWEGMIAGWFGYTSHGAHGVAVAADLKSTQEAINKITKNLNSLSELEVKNLYRLSYAMDELHNEILELDEKVDDLRADTISSQIELAVLLSNEGIINWEDQFLLALERKLKKMLGPSAVEIGNGCFETKHKCNQTCLDKIAAGTFDAGEFSLPTFDSLNITA

Claims

1. An isolated mutant influenza hemagglutinin polypeptide comprising at least one stabilizing mutation in at least one of the unstable regions (a)-(e) in said polypeptide, wherein said at least one stabilizing mutation comprises a substitution mutation at the following positions: (a) Amino acid positions 227, 229, and / or 238; and / or (b) Amino acid positions 329 and / or 426; and / or (c) Amino acid positions 384, 402, 472, and / or 476; and / or (d) Amino acid positions 468, 471, 475, and / or 478; and / or (e) Amino acid positions 235, 430, and / or 433; wherein said amino acid positions correspond to the amino acid positions of SEQ ID NO:

1.

2. The isolated mutant influenza hemagglutinin polypeptide according to claim 1, comprising at least two stabilizing mutations in at least one of the unstable regions (a)-(e) in said polypeptide.

3. The isolated mutant influenza hemagglutinin polypeptide according to claim 1, comprising at least two stabilizing mutations in two, three, four, or five of the unstable regions (a)-(e) in said polypeptide.

4. The isolated mutant influenza hemagglutinin polypeptide according to claim 1, comprising two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen stabilizing mutations.

5. The isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 4, wherein (a) Amino acid position 227 is substituted with an amino acid selected from the group consisting of T, L, R, Q, F, I, and Y; amino acid position 229 is substituted with amino acid L; and / or Amino acid position 238 is substituted with amino acid F; and / or (b) Amino acid position 329 is substituted with an amino acid selected from the group consisting of M, W, and F; and / or amino acid position 426 is substituted with an amino acid selected from the group consisting of F, W, Y, and P; and / or (c) Amino acid position 384 is substituted with an amino acid selected from F or Y; amino acid position 402 is substituted with amino acid A; amino acid position 472 is substituted with an amino acid selected from the group consisting of W, R, F, K, or L; and / or amino acid position 476 is substituted with amino acid F; and / or (d) Amino acid position 468 is substituted with amino acid L; amino acid position 471 is substituted with an amino acid selected from V or Q; amino acid position 475 is substituted with an amino acid selected from the group consisting of Q, N, W, F, and L; and / or amino acid position 478 is substituted with an amino acid selected from W or R; and / or (e) Amino acid position 235 is substituted with amino acid W; amino acid position 430 is substituted with an amino acid selected from L or Y; and / or amino acid position 433 is substituted with amino acid P.

6. The isolated mutant influenza hemagglutinin polypeptide according to claim 5, wherein (a) Amino acid position 384 is substituted with F and amino acid position 475 is substituted with W; (b) Amino acid position 384 is substituted with F and amino acid position 475 is substituted with Q; (c) The amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by K, and the amino acid at position 476 is replaced by F; (d) The amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (e) The amino acid at position 384 is replaced by Y, the amino acid at position 402 is replaced by A, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (f) The amino acid at position 476 is replaced by F and the amino acid at position 475 is replaced by W; (g) The amino acid at position 476 is replaced by F and the amino acid at position 475 is replaced by Q; (h) The amino acid at position 227 is replaced by T and the amino acid at position 426 is replaced by Y; (i) The amino acid at position 227 is replaced by T and the amino acid at position 430 is replaced by Y; (j) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 430 is replaced by Y; (k) The amino acid at position 227 is replaced by T and the amino acid at position 475 is replaced by W; (l) The amino acid at position 227 is replaced by T and the amino acid at position 475 is replaced by Q; (m) The amino acid at position 227 is replaced by T and the amino acid at position 384 is replaced by F; (n) The amino acid at position 227 is replaced by T and the amino acid at position 476 is replaced by F; (o) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 475 is replaced by W; (p) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 475 is replaced by Q; (q) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 475 is replaced by W, and the amino acid at position 430 is replaced by Y; (r) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y; (s) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, and the amino acid at position 384 is replaced by F; and / or (t) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W; (u) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by W, and the amino acid at position 430 is replaced by Y; (v) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by Q; (w) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 384 is replaced by F, the amino acid at position 475 is replaced by Q, and the amino acid at position 430 is replaced by Y; (x) The amino acid at position 227 is replaced by T and the amino acid at position 235 is replaced by W; (y) The amino acid at position 475 is replaced by W and the amino acid at position 426 is replaced by Y; (z) The amino acid at position 475 is replaced by W and the amino acid at position 430 is replaced by Y; (aa) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by R; (bb) The amino acid at position 475 is replaced by Q and the amino acid at position 478 is replaced by F; (cc) The amino acid at position 426 is replaced by Y and the amino acid at position 384 is replaced by F; (dd) The amino acid at position 426 is replaced by Y and the amino acid at position 476 is replaced by F; (ee) The amino acid at position 426 is replaced by Y and the amino acid at position 455 is replaced by A; (ff) The amino acid at position 426 is replaced by Y and the amino acid at position 329 is replaced by W; (gg) The amino acid at position 430 is replaced by Y and the amino acid at position 384 is replaced by F; (hh) The amino acid at position 430 is replaced by Y and the amino acid at position 476 is replaced by F; (ii) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by Y; (jj) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by W; (kk) The amino acid at position 430 is replaced by Y and the amino acid at position 426 is replaced by F; (ll) The amino acid at position 433 is replaced by P and the amino acid at position 430 is replaced by Y; (mm) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by Y; (nn) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by W; (oo) The amino acid at position 433 is replaced by P and the amino acid at position 426 is replaced by F; (pp) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, and the amino acid at position 475 is replaced by W; (qq) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 402 is replaced by A, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by R, and the amino acid at position 476 is replaced by F; (rr) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by F, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R; (ss) The amino acid at position 227 is replaced by T, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 468 is replaced by L, amino acid 471 is replaced by V; the amino acid at position 472 is replaced by W, the amino acid at position 475 is replaced by F, and the amino acid at position 478 is replaced by R; (tt) The amino acid at position 227 is replaced by T, the amino acid at position 384 is replaced by F, the amino acid at position 426 is replaced by Y, the amino acid at position 430 is replaced by Y, the amino acid at position 472 is replaced by W, and the amino acid at position 476 is replaced by F; (uu)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; amino acid 471 is substituted with V; at amino acid position 472, W is substituted; at amino acid position 475, L is substituted; and at amino acid position 478, R is substituted; (vv)At amino acid position 227, T is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 468, L is substituted; amino acid 471 is substituted with Q; at amino acid position 472, W is substituted; at amino acid position 475, Q is substituted; and at amino acid position 478, R is substituted; (ww)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, K is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted; (xx)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, L is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted; (yy)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 471, Q is substituted; at amino acid position 472, R is substituted; and at amino acid position 476, F is substituted; (zz)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, W is substituted; at amino acid position 475, Q is substituted; and at amino acid position 476, F is substituted; (aaa)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, W is substituted; and at amino acid position 476, F is substituted; or (bbb)At amino acid position 227, T is substituted; at amino acid position 384, F is substituted; at amino acid position 402, A is substituted; at amino acid position 426, Y is substituted; at amino acid position 430, Y is substituted; at amino acid position 472, R is substituted; at amino acid position 475, W is substituted; and at amino acid position 476, F is substituted.

7. An isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 6, wherein the mutant influenza hemagglutinin polypeptide further comprises an introduced cleavage site.

8. An isolated mutant influenza hemagglutinin polypeptide according to claim 7, wherein the introduced cleavage site is a furin cleavage site.

9. The isolated mutant influenza hemagglutinin polypeptide according to claim 8, wherein the furin cleavage site is introduced by mutating amino acid positions 359-361 of the polypeptide, or wherein the furin cleavage site is introduced by an insertion at the amino terminus of amino acid position 362, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:

1.

10. The isolated mutant influenza hemagglutinin polypeptide according to claim 8 or 9, further comprising an insertion at the carboxyl terminus of the RSV p27 peptide (SEQ ID NO:2) at amino acid position 362.

11. The isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 9, wherein the amino acid at position 362 is substituted with Q.

12. The isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 11, further comprising a deletion of the signal peptide at the amino terminus of the polypeptide.

13. The isolated mutant influenza hemagglutinin polypeptide according to claim 12, wherein the signal peptide comprises amino acid positions 1-15 of the polypeptide.

14. The isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 13, wherein the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46-48, 63, 67-75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204-208, 216, 219-222.

15. The isolated mutant influenza hemagglutinin polypeptide according to claim 14, wherein the mutant influenza hemagglutinin polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, 9, 35, 46-48, 63, 67-75, 142, 146, 150, 154, 158, 162, 166, 170, 174, 178, 181, 186, 189, 201, 202, 204-208, 216, 219-222, and wherein the mutant influenza hemagglutinin polypeptide comprises a deletion of the signal peptide at the amino terminus of the polypeptide.

16. The isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 15, wherein the mutant influenza hemagglutinin polypeptide further comprises a carboxyl (C) terminus truncation starting at amino acid positions from amino acid position 536 to amino acid position 585, wherein the amino acid positions correspond to the amino acid positions of SEQ ID NO:

1.

17. An isolated nucleic acid encoding the isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 16.

18. An isolated vector comprising the isolated nucleic acid according to claim 17.

19. An isolated host cell comprising the vector according to claim 18.

20. A pharmaceutical composition comprising the isolated mutant influenza hemagglutinin polypeptide according to any one of claims 1 to 16 and a pharmaceutically acceptable carrier.

21. A pharmaceutical composition comprising the isolated nucleic acid according to claim 17.

22. A pharmaceutical composition comprising the isolated vector according to claim 18.

23. A method of inducing an immune response against an influenza virus in a subject in need thereof, the method comprising administering to the subject in need thereof a pharmaceutical composition according to any one of claims 20 to 22.

24. A method of producing an isolated mutant influenza hemagglutinin polypeptide, the method comprising culturing the isolated host cell according to claim 19 under conditions capable of producing the mutant influenza hemagglutinin polypeptide, and recovering the mutant influenza hemagglutinin polypeptide from the cells or the culture.

25. A method of producing the pharmaceutical composition according to claim 20, the method comprising combining the isolated mutant influenza polypeptide with a pharmaceutically acceptable carrier.

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