Norovirus-like particles with improved stability

Abstract

To provide norovirus VLPs, notably VLPs of genogroup I, with improved stability, and capsid proteins for such VLPs.SOLUTION: The invention provides a VP1 capsid protein of norovirus genogroup I having an amino acid sequence wherein the amino acid sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr in the P domain is modified to Ala-Ala-Leu-LeuNal-Arg / Lys-Tyr.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention provides a VP1 capsid protein of Norovirus (NoV) genogroup I, capable of forming a VLP (virus-like particle). The present invention further provides a VLP containing the capsid protein, as well as immunogenic compositions and vaccines containing the capsid protein or the VLP. The present invention further provides immunogenic compositions and vaccines containing the capsid protein or the VLP and a capsid protein or VLP of genogroup II or genogroup IV. The present invention further provides use of the composition and vaccine for preventing or treating a norovirus infection in a subject, preferably a human. Further provided is a method for preventing or treating a norovirus infection in a subject (preferably a human), comprising administering the composition or vaccine to the subject. Also provided is a method for increasing the stability of a norovirus genogroup I VLP. [Background technology]

[0002] Noroviruses are the leading cause of gastroenteritis outbreaks worldwide. They are responsible for 685 million cases annually, including 200 million cases in children under 5 years of age (www.cdc.gov / norovirus / worldwide.html). To date, there are no commercially available norovirus vaccines. There are also no established protocols for norovirus culture, which have significantly slowed progress in norovirus vaccine development. Furthermore, rapid genetic change in circulating noroviruses leads to the emergence of novel norovirus strains every 2–4 years, which can cause outbreaks and complicate the development of vaccines and treatments needed to combat these exposures (de Graaf, M, van Beek, J, & Koopmans, PG, 2016, Nature Rev Microbiol, 14:421–433). It is clear that representatives of genogroups GI and GII have been the primary drivers of most outbreaks over the past 20 years, with the prevalence of genotype 4 (GII.4) of the GII genogroup increasing (Matthews et al., 2012, Epidemiol. Infect, 140:1161-1172). For example, since 2014, the emergence of novel GII.17 strains and the re-emergence of older GII.4 strains have been described in East Asia (Chan et al., 2015, Nat Commun, doi:10.1038 / ncomms10061; Choi et al., 2017, Food Environ Virol, doi:10.1007 / s12560-017-9278-4). This constantly changing landscape further complicates the definition of effective vaccine compositions, making the use of multivalent vaccines the generally preferred approach.Current norovirus vaccine development relies primarily on the use of virus-like particle (VLP) vaccines produced in animal cell culture, particularly insect cells using the baculovirus expression system (Huhti, L. et al., 2013, Arch. Virol., 158:933-942; Koho, T. et al., 2012, J. Virol. Methods, 181:6-11) (for recent reviews, see: Tan, M. & Jiang, X., 2014, Hum. Vaccin Immunother, 10:1449-1456; Debbink, K., Lindesmith, L. & Baric, R.S., 2014, Clin. Infect. Dis, 58:1746-1752; Ramani, S., Estes, M.K. & Atmar, R.L., 2016, PLoS Pathog, 12:e1005334).

[0003] A major challenge in developing a multi-antibody vaccine is that even relatively closely related norovirus isolates exhibit distinct VLP stability profiles (Pogan, R. et al., 2018, Curr Opin Virol, in press; Pogan, R. et al., 2018 J. Phys.: Condens. Matter, 30:064006). Therefore, preparing a multivalent vaccine consisting of a mixture of different VLPs, each of which requires different buffer conditions due to its different stability profiles, presents a significant formulation challenge. In some cases, this problem is resolved by adding alum to the VLP mixture as a stabilizer and adjuvant (Leroux-Roels, G. et al., 2018, The J. Infect. Diseases, 217:597-607). However, despite the fact that alum-containing vaccines are generally well tolerated, alum has long-term biopersistence in the body, the ability to migrate into lymphoid organs, and the ability to accumulate in the brain, which raises concerns, especially for pediatric applications (Petrovsky, N. & Aguilar, JC., 2004, Immunol. & Cell Biol., 82:488-496; Gherardi RK et al., 2014, Front. Neurol., 6:4; Gherardi RK et al., 2016, Morphologie, 100:85-94). An alternative approach is amino acid substitution of critical residues resulting in more uniform VLPs (Someya, Y. et al., 2011, Journal of General Virology, 92:2320-2323), which may also improve VLP stability even in more complex formulations of VLP mixtures (Pogan, R. et al., 2018, J. Phys.: Condens. Matter, 30:064006). Summary of the Invention

[0004] Departing from the prior art, it is an object of the present invention to provide norovirus VLPs, particularly genogroup I VLPs, and capsid proteins for such VLPs, with improved stability. Another object is to provide bivalent or multivalent immunogenic compositions and vaccines that address the compatibility and stability challenges of norovirus VLPs to enable the formulation of vaccine compositions without the need for stabilizers such as alum. Accordingly, it is also an object to provide compositions comprising NoV VLPs of different genogroups with equivalent or similar stability. Another object is to provide protocols for the purification, preparation, and formulation of VLPs, particularly VLPs of different genogroups, such as genogroups I and II.

[0005] These objectives are achieved by: 1. A VP1 capsid protein of Norovirus genogroup I, wherein the amino acid sequence of said protein has an Arg or Lys residue at the position corresponding to Arg472 in SEQ ID NO:3. 2. VP1 capsid protein of Norovirus genogroup I, having the amino acid sequence in which the amino acid stretch Ala-Ala-Leu-Leu / Val-His-Tyr (SEQ ID NO: 57) is modified to Ala-Ala-Leu-Leu / Val-Arg / Lys-Tyr (SEQ ID NO: 58), wherein Leu / Val means either Leu or Val and Arg / Lys means either Arg or Lys. 3. The capsid protein according to item 2, wherein the amino acid sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr-Val / Leu / Ile-Asp (SEQ ID NO: 59) is modified to Ala-Ala-Leu-Leu / Val-Arg / Lys-Tyr-Val / Leu / Ile-Asp (SEQ ID NO: 60), wherein Val / Leu / Ile means either Val or Leu or Ile. 4. The capsid protein of any one of items 1 to 3, wherein the capsid protein belongs to any of the following genogroup I genotypes: GI.1, GI.2, GI.3, GI.4, GI.5, GI.6, GI.7, GI.8, or GI.9. 5. The capsid protein according to any one of items 1 to 4, wherein the capsid protein is capable of associating to form a Norovirus-like particle (Norovirus virus-like particle). 6. The capsid protein according to any one of items 1 to 5, wherein the capsid protein has an amino acid sequence as defined in any one of SEQ ID NOs: 6 to 21, except that the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg or Lys; or the capsid protein has an amino acid sequence as defined in any one of SEQ ID NOs: 3 to 5. 7. (i) the amino acid sequence of the protein consists of or comprises at least 480, preferably at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21, except that the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg or Lys; or (ii) the amino acid sequence of the protein consists of or comprises at least 480, preferably at least 500, amino acid residues and has at least 80%, preferably at least 85%, more preferably at least 90% sequence identity over this length to a sequence segment of at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21; or (iii) the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, more preferably 1 to 30 deletions, substitutions, additions or insertions compared to a sequence segment of at least 480, preferably at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21; 7. The capsid protein according to any one of items 1 to 6, wherein in item (ii) or (iii), the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg or Lys. 8. The capsid protein according to item 7, wherein the amino acid sequence of the protein comprises at least 510, preferably at least 520, more preferably at least 530, and most preferably at least 540 amino acid residues. 9. (i') the amino acid sequence of the protein consists of or comprises the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4 or 5; or (ii') the amino acid sequence of the protein has at least 80%, preferably at least 85%, and more preferably at least 90% sequence identity to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; or (iii') the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, and more preferably 1 to 30 deletions, substitutions, additions, or insertions compared to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; 7. The capsid protein according to any one of items 1 to 6, wherein in item (ii') or (iii'), the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3 or the amino acid at the position corresponding to His472 in SEQ ID NO: 2 is Arg or Lys. 10. (i'') the amino acid sequence of the protein consists of or comprises the amino acid sequence of SEQ ID NO: 3, 4 or 5; or (ii'') the amino acid sequence of the protein has at least 80%, preferably at least 85%, more preferably at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 3, 4 or 5; or (iii'') the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, and more preferably 1 to 30 deletions, substitutions, additions, or insertions compared to the amino acid sequence of SEQ ID NO: 3, 4, or 5; 10. The capsid protein according to any one of items 1 to 9, wherein in item (ii") or (iii"), the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3 or the amino acid at the position corresponding to His472 in SEQ ID NO: 2 is Arg or Lys. 11. The protein is (i''') a polypeptide having an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 3, 4, or 5 from residue 43 to residue 540; or (ii''') comprises a polypeptide having an amino acid sequence that has at least 80%, preferably at least 85%, and more preferably at least 90% sequence identity to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; or (iii''') a polypeptide having an amino acid sequence having 1 to 50, preferably 1 to 40, more preferably 1 to 30 deletions, substitutions, additions or insertions compared to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4 or 5; In item (ii) or (iii), 7. The capsid protein of any one of items 1 to 6, wherein the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3 or the amino acid at the position corresponding to His472 in SEQ ID NO: 2 is Arg or Lys. 12. A VP1 capsid protein as defined in items (i) to (iii) of paragraph 7, as defined in items (i') to (iii') of paragraph 9, as defined in items (i'') to (iii'') of paragraph 10, or as defined in items (i''') to (iii''') of paragraph 11. 13. A nucleic acid molecule encoding the capsid protein of any one of items 1 to 12. 14. A virus-like particle (VLP) consisting of or comprising a capsid protein according to any one of items 1 to 12. 15. The VLP of item 14, wherein the VLP comprises at least 60, preferably at least 90, more preferably about 180 molecules of the protein. 16. An immunogenic composition comprising a capsid protein as defined in any one of items 1 to 12 or a VLP of item 14 or 15 and optionally a pharmaceutically acceptable carrier. 17. The immunogenic composition according to item 16, further comprising a Norovirus genogroup II VP1 capsid protein or a VLP consisting of or comprising a genogroup II VP1 capsid protein. 18. A vaccine against norovirus infection, comprising the immunogenic composition of item 16 or 17. 19. A vaccine against norovirus infection comprising a capsid protein as defined in any one of items 1 to 12 or a VLP as defined in item 14 or 15. 20. The vaccine according to item 18 or 19, comprising a Norovirus genogroup II VP1 capsid protein or a VLP consisting of or comprising a genogroup II VP1 capsid protein. 21. The vaccine according to item 20, comprising a VP1 capsid protein of genogroup I and a VP1 capsid protein of genogroup II in a mass ratio of 5:1 to 1:5, preferably 3:1 to 1:3, more preferably 2:1 to 1:2. 22. The vaccine of any one of items 18 to 21, further comprising an adjuvant. 23. A capsid protein as defined in any one of items 1 to 12, or a VLP of item 14 or 15, or a vaccine as defined in any one of items 18 to 22, for use in the prevention or treatment of a Norovirus infection in a subject. 24. A method for preventing or treating a Norovirus infection in a subject, comprising administering to the subject one or more doses of a capsid protein as defined in any one of items 1 to 12, or a VLP as defined in item 14 or 15, or a vaccine as defined in any one of items 18 to 22. 25. A method for increasing the stability of norovirus genogroup I VLPs, comprising replacing His residues in the sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr (SEQ ID NO: 57) in the P domain of genogroup I VP1 capsid protein with Arg or Lys. 26. The method of claim 25, comprising expressing the capsid proteins defined in any one of claims 1 to 12 from a nucleic acid molecule encoding the capsid proteins and allowing the expressed capsid proteins to assemble to form a VLP. 27. A method for producing a Norovirus genogroup I VLP, comprising expressing a capsid protein as defined in any one of items 1 to 12 from a nucleic acid molecule encoding the capsid protein, and allowing the expressed capsid proteins to associate to form a VLP.

[0006] The present inventors have found that the stability of Norovirus (NoV) genogroup I VLPs is lower than that of genogroup II NoV VLPs. This poses a problem for providing stable VLP compositions and vaccines containing genogroup I VLPs. The present inventors have further discovered a means to enhance the stability of NoV genogroup I VLPs by modifying the amino acid sequence of the genogroup I VP1 capsid protein. The modified VP1 capsid protein is the capsid protein or antigen of the present invention. Thus, the stability of VLPs formed from the VP1 protein of the present invention is improved. The improved stability is demonstrated by the results reported in Example 3 and in Figures 9 and 10. Figure 9 shows the improved homogeneity and purity of the VLPs of the present invention by size exclusion chromatography. Figure 10 shows the stability trend and improved purity of the capsid protein of the present invention (B) compared to the original capsid protein (A).

[0007] Furthermore, when preparing immunogenic compositions or vaccines containing both genogroup I and genogroup II or IV VLPs, the stability of the genogroup I VLPs and the genogroup II or IV VLPs can be made more similar, thereby making compositions containing both types of VLPs more stable, thereby extending their shelf life and allowing for the use of less stringent storage conditions (e.g., refrigerated instead of frozen) during storage and transportation of the vaccines of the present invention. [Brief explanation of the drawings]

[0008] [Figure 1A] Figure 1A shows an alignment of norovirus capsid protein VP1 from different strains of genogroup I norovirus. The (S / A / T / V)TA(V / A / T / L)ATA motif and the conserved histidine residues in the genogroup I sequences are boxed. Figure 1A shows an alignment of the norovirus GI of the N-terminal portion of the VP1 protein. The sequences shown are partial sequences of the complete VP1 amino acid sequence given in the "Amino Acid Sequence" section below and in the Electronic Sequence Listing. [Figure 1B] Figure 1B shows an alignment of norovirus capsid protein VP1 from different strains of genogroup I norovirus. The (S / A / T / V)TA(V / A / T / L)ATA motif and the conserved histidine residues in the genogroup I sequences are boxed. Figure 1B shows an alignment of the norovirus GI of the C-terminal portion of the VP1 protein. The sequences shown are subsequences of the complete VP1 amino acid sequence given in the "Amino Acid Sequence" section below and in the Electronic Sequence Listing. [Figure 2]Figure 1 shows an alignment of the N-terminal portion of norovirus capsid protein VP1 from different strains of genogroups I, II, and IV. Sequences from different genogroups are separated by horizontal lines. The (S / A / T / V)TA(V / A / T / L)ATA motif in genogroup I and its corresponding region in genogroup II and IV sequences are boxed. The sequence shown is a subsequence of the complete VP1 amino acid sequence given in the "Amino Acid Sequence" section below and in the Electronic Sequence Listing. [Figure 3] Panel A shows a slab through the structure of a GI norovirus-like particle (PDB: 1IHM, white: protruding domain; gray: shell domain; black: inner surface). Panel B shows only the inner surface of the VLP (PDB: 1IHM, amino acid residues 29-45). Panel C represents a portion of panel B and illustrates the placement of the two conserved threonine residues of the (S / A / T / V)TA(V / A / T / L)ATA motif of genogroup I on the inner surface of the VLP. Substitution of the two threonine residues with lysine and aspartic acid residues on the inner surface of the VLP may result in the formation of ionic interactions or salt bridges that enhance stability. [Figure 4] Figure 1 shows an alignment of the C-terminal portion of norovirus capsid protein VP1 from different strains of genogroups I, II, and IV. Sequences from different genogroups are separated by horizontal lines. The conserved histidine residue in genogroup I and the conserved arginine residue in genogroups II and IV sequences are boxed. The sequences shown are subsequences of the complete VP1 amino acid sequence given in the "Amino Acid Sequence" section below and in the Electronic Sequence Listing. [Figure 5]Figure 1 shows the structure of a portion of the protrusion domain (top) and shell domain (bottom) of Genogroup I VP1 (PDB: 1IHM) and the theoretical structure of the same region of Genogroup II VP1. The conserved histidine residues in Genogroup I and the conserved arginine residues in Genogroup II VP1 are indicated by arrows. The arginine residues in Genogroup II VP1 may be involved in ionic interactions or salt bridges between the protrusion and shell domains, thereby contributing to the assembly and stability of Genogroup II VP1-based virus-like particles. [Figure 6A] Figure 1 shows a schematic diagram of the cloning of wild-type, NC, and NCHR norovirus GI.4 Chiba VP1. The norovirus GI.4 Chiba VP1 sequence module is cloned into a TMV-based viral binary expression vector using the type IIS enzyme Bsal. The amino acid sequence region encoded by the module is indicated. The overhangs flanking the module after Bsal restriction digestion are indicated. [Figure 6B] Figure 1 shows a cloning scheme for NCHRKD and NCHRDK. The sequence module of norovirus GI.4 Chiba VP1 is cloned into a TMV-based viral binary expression vector using the type IIS enzyme Bsal. The amino acid sequence region encoded by the module is indicated. The overhangs flanking the module after Bsal restriction digestion are indicated. [Figure 7]FIG. 1 shows the expression of wild-type and mutant versions of GI.4 Chiba 407 VP1 in Nicotiana benthamiana using magnICON®. Laemmli total protein extracts were separated on a 12% polyacrylamide gel and subsequently stained with Coomassie (M: size marker; 0: uninfiltrated plant tissue; 1: GI.4 Chiba 407 VP1 wild type; 2: GI.4 Chiba 407 VP1 with a single initiation methionine residue and deletion of two C-terminal arginine residues; 3: GI.4 Chiba 407 VP1 with a single initiation methionine residue and H472R and deletion of two C-terminal arginine residues; 4: GI.4 Chiba 407 VP1 with a single initiation methionine residue, T39K, T43D, and H472R and deletion of two C-terminal arginine residues; 5: GI.4 Chiba 407 VP1 with a single initiation methionine residue, T39D, T43K, and H472R and deletion of two C-terminal arginine residues). The asterisk indicates the signal corresponding to GI.4 Chiba 407 VP1. [Figure 8] GI.4 Transmission electron micrographs of two independent VLP batches, each prepared using the wild-type, NC, or NCHR version of Chiba 407 VP1. GI.4 Transmission electron micrographs of UranyLess-stained VLP samples prepared from A) wild-type, B) NC, and C) NCHR versions of Chiba 407 VP1. The bar in the lower right of the image represents 500 nm. [Figure 9] Figure 1 shows SE-HPLC of VLPs derived from the NC and NCHR versions of GI.4 Chiba 407 VP1. Size-exclusion high-performance liquid chromatography to analyze VLP formation in samples prepared from A) the NC version and B) the NCHR version of GI.4 Chiba 407 VP1. The black arrow indicates a second, smaller VLP species in the NC sample of GI.4 Chiba 407 VP1. [Figure 10]Figure 1 shows the stability of the NC and NCHR versions of GI.4 Chiba 407. Stability trends of A) the NC and B) the NCHR versions of GI.4 Chiba 407 as shown by VLP content in % (measured using SE-HPLC) and VP1 purity in % (measured using capillary gel electrophoresis). [Figure 11] Figure 1 shows a comparison of the immunogenicity of the GI.4 Chiba 407 NC and NCHR versions. A) Titration of homologous norovirus VP1 antigen-specific serum IgG. Individual, serially diluted serum samples from immunized mice were analyzed for antibody levels at week 5 in an ELISA. Mean endpoint titration curves for antibodies induced against GI.4 Chiba after administration of 10 μg of GI.4 Chiba NC or GI.4 Chiba NCHR VLPs are shown. B) Using a porcine gastric mucin-based blocking assay, two-fold pooled serum samples per group were tested for genotype-specific blocking (neutralizing) activity against the homologous GI.4 Chiba mutant VLPs. The blocking index (%) was calculated as 100% - [(OD of wells containing VLPs and serum / OD of wells without serum, "maximum binding") × 100%]. DETAILED DESCRIPTION OF THE INVENTION

[0009] Noroviruses are non-enveloped, single-stranded, positive-sense RNA viruses. They belong to the Calciviridae family. The norovirus genome consists of three open reading frames (ORFs). ORF1 encodes nonstructural proteins essential for viral replication, while ORF2 and ORF3 encode the major capsid protein VP1 and the minor structural protein VP2, respectively. VP1 self-assembles into virus-like particles (VLPs), which are morphologically and antigenically similar to native virions. Because NoVs cannot be cultivated in cell culture, most of our understanding of the biology of human NoVs has come from studies using VLPs.

[0010] Noroviruses are classified into five different genogroups (GI, GII, GIII, GIV, and GV), which can be further divided into genotypes. Genotypes are classified and designated by Arabic numerals, often preceded by the Roman numeral designation of the genogroup. Examples of noroviruses include Norwalk virus (GenBank: AF093797.1), GI.1 strain Aichi / 124-89 / JP (GenBank: BAA834130), GI.2 strain Funabashi258 / 96 / JP (GenBank: BAC05516), Maryland virus (MV, AY032605), GI.3 strain Shimizu / KK2866 / JP (GenBank: AII73765), GI.4 strain Chiba407 / 87 / JP (GenBank: BAA82106), GI.7 strain TCH-060 / USA / 2003 (GenBank: AEQ77282), GII.3 strain Kashiwa336 / 00 / JP (GenBank: AAZ66774), and GII.4 strain NL / 2014 / Groninge (GenBank: GII.4). n01 (GenBank: CRL46961), GII.4 strain Sydney / NSW0514 / 2012 / AU (GenBank: AFV08795), GII.4 strain Aomori2 / 2006 / JP (GenBank: BAG70446), GII.17 strain JP / 2002 / Saitama / T87 (GenBank: AII73747), Jena virus (JV, AJ 01099), GII.17 strain JP / 2013 / / Saitama5203 (GenBank: BAR63715), Seto virus (GenBank: AB031013), GII.17 strain C142 / 1978 / GUF (GenBank: AGI17592), and GIV.1 strain Ahrenshoop246 / DEU / 2012 (GenBank: AFN61315). There are many other norovirus strains, whose complete genomes are annotated in publicly available databases (www.viprbrc.org).

[0011] The basic structural component of norovirus particles is the VP1 capsid protein. Another capsid protein is VP2, which is not required for the assembly of viral particles or VLPs. NoV particle size varies between 23 and 40 nm in diameter. Depending on size, the number of VP1 molecules per viral particle is generally either 60 or 180 molecules (http: / / viralzone.expasy.org / 194).

[0012] In the absence of viral genetic material, the VP1 capsid protein can assemble into virus-like particles (VLPs), which resemble virus particles in size and shape but do not contain the NoV genome. VP1 alone (in the absence of VP2) is sufficient to form VLPs. Thus, herein, a VLP contains VP1 protein molecules and may further contain VP2 protein molecules. In a preferred embodiment, the VLPs of the present invention contain VP1 capsid protein molecules but no VP2 protein molecules.

[0013] The NoV capsid protein VP1 has two domains: the shell (S) domain formed by amino acid residues 1-225 in the Norwalk virus capsid protein (SEQ ID NO: 10), and the protrusion (P) domain formed by residues 225-530 (Choi et al., PNAS 105 (2008) 9175-9180). See also Figure 3. While the S domain is involved in the formation of the icosahedral shell of the NoV capsid, the P domain is involved in the dimerization contact of the VP1 protein. The P domain dimer protrudes from the icosahedral shell. The P domain is further subdivided into P1 and P2 subdomains. In the Norwalk virus VP1 capsid protein, amino acid residues 225-278 and 406-519 form the P1 subdomain, and residues 279-405 form the terminal P2 subdomain (Choi et al., ibid.). In the case of the Chiba protein of SEQ ID NO: 3, residues 1-224 constitute the S domain, residues 224-540 constitute the P domain, residues 224-277 and 414-531 constitute the P1 domain, and residues 278-413 constitute the P2 domain. The S, P, P1, and P2 domains of other genogroup I VP1 proteins, such as those of SEQ ID NOs: 6-21, can be determined by sequence alignment to find the major corresponding sequence segments that form the mentioned domains.

[0014] VP1 capsid protein of norovirus genogroup I of the present invention The present inventors have discovered mutants of NoV genogroup I VP1 proteins that can assemble into VLPs with improved stability. The present invention therefore provides NoV genogroup I VP1 proteins. These VP1 proteins are capable of assembling or assembling into more stable VLPs. In one embodiment, a genogroup I VP1 protein of the present invention has an Arg or Lys residue, preferably an Arg residue, at a position corresponding to a histidine residue highly conserved among genogroup I VP1 proteins. This position is position 474 in SEQ ID NO:1 or position 472 in SEQ ID NO:2 or 3. Corresponding positions in other genogroup I VP1 proteins can be confirmed by aligning amino acid sequences of at least 500 amino acids to SEQ ID NO:3. Accordingly, the present invention provides NoV genogroup I VP1 capsid proteins, wherein the amino acid sequence of the protein has an Arg or Lys residue, preferably an Arg residue, at a position corresponding to His472 in SEQ ID NO:2 or Arg472 in SEQ ID NO:3, 4, or 5. Herein, the amino acid sequence shown in SEQ ID NO: 3 is a preferred reference sequence for identifying the positions at which the capsid protein of the present invention has an Arg or Lys residue in the VP1 sequence.

[0015] The His amino acid in the VP1 protein of NoV genogroup I corresponding to position 474 in SEQ ID NO: 1 or position 472 in SEQ ID NO: 2 is part of the sequence stretch Ala-Ala-Leu-Leu / Val-His-(SEQ ID NO: 61), preferably Ala-Ala-Leu-Leu / Val-His-Tyr (SEQ ID NO: 57). This sequence stretch is present in the P domain of the VP1 protein, preferably in the P1 subdomain of the VP1 protein. Therefore, the VP1 capsid protein of NoV genogroup I of the present invention can be defined as follows: The VP1 capsid protein of NoV genogroup I of the present invention has an amino acid sequence in which the amino acid sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr (SEQ ID NO: 57) in the P domain, preferably in the P1 domain, is modified to Ala-Ala-Leu-Leu / Val-Arg / Lys-Tyr (SEQ ID NO: 58), where Leu / Val means either Leu or Val and Arg- / Lys means Arg or Lys. Preferably, the amino acid sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr-Val / Leu / Ile-Asp (SEQ ID NO: 59) in the P domain is modified to Ala-Ala-Leu-Leu / Val-Arg / Lys-Tyr-Val / Leu / Ile-Asp (SEQ ID NO: 60), where Val / Leu / Ile means either Val, Leu, or Ile. Preferably, the amino acid sequence of said protein comprises at least 510, preferably at least 520, more preferably at least 530 amino acid residues.

[0016] The VP1 capsid protein of the present invention is a protein of NoV genogroup I. Norovirus classification is based on the VP1 protein (Hansman et al., Journal of General Virology (2006), 87, 909-919). Therefore, established NoV classification methods can be used to determine whether a given NoV VP1 capsid protein is a genogroup I capsid protein.

[0017] Embodiments of the VP1 capsid protein of the present invention are as follows: (i) the amino acid sequence of the protein consists of or comprises at least 500 contiguous amino acid residues of any one of the amino acid sequences of SEQ ID NOs: 6 to 21, except that the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg or Lys; or (ii) the amino acid sequence of the protein consists of or comprises at least 500 amino acid residues and has at least 80%, preferably at least 85%, more preferably at least 90%, even more preferably at least 95% sequence identity over this length to a sequence segment of at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21; or (iii) the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, more preferably 1 to 30, and even more preferably 1 to 20 deletions, substitutions, additions, or insertions compared to a sequence segment of at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21; In item (ii) or (iii), the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 (or residue 469 in SEQ ID NO: 6) is Arg or Lys, preferably Arg. In these embodiments, the minimum number of contiguous amino acid residues is preferably 510, more preferably 520, even more preferably 530, and most preferably 540 amino acid residues.

[0018] Other VP1 capsid protein embodiments of the invention are as follows: (i') the amino acid sequence of the protein consists of or comprises the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4 or 5; or (ii') the amino acid sequence of the protein has at least 80%, preferably at least 85%, more preferably at least 90%, and most preferably at least 95% sequence identity to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; or (iii') the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, more preferably 1 to 30, and even more preferably 1 to 20 deletions, substitutions, additions, or insertions compared to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; In item (ii') or (iii'), the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3, 4 or 5 is Arg or Lys, preferably Arg, respectively.

[0019] A more preferred embodiment of the amino acid sequence of the VP1 capsid protein is as follows: (i'') the amino acid sequence of the protein consists of or comprises the amino acid sequence of SEQ ID NO: 3, 4 or 5; (ii'') the amino acid sequence of the protein has at least 80%, preferably at least 85%, more preferably at least 90%, and most preferably at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 3, 4, or 5; (iii'') the amino acid sequence of the protein has 1 to 50, preferably 1 to 40, more preferably 1 to 30, and even more preferably 1 to 20 deletions, substitutions, additions, or insertions compared to the amino acid sequence of SEQ ID NO: 3, 4, or 5; In item (ii'') or (iii''), the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3, 4 or 5 is Arg or Lys, preferably Arg, respectively.

[0020] In other embodiments, the capsid protein is (i''') comprising a polypeptide molecule consisting of an amino acid sequence comprising the amino acid sequence of residues 43 to 540 of SEQ ID NO: 3, 4, or 5; or (ii''') comprising a polypeptide molecule consisting of an amino acid sequence having at least 80%, preferably at least 85%, more preferably at least 90%, and most preferably at least 95% sequence identity to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; or (iii''') comprising a polypeptide molecule consisting of an amino acid sequence having 1 to 50, preferably 1 to 40, more preferably 1 to 30, and even more preferably 1 to 20 deletions, substitutions, additions, or insertions compared to the amino acid sequence from residue 43 to residue 540 of SEQ ID NO: 3, 4, or 5; is defined by In item (ii''') or (iii'''), the amino acid at the position corresponding to Arg472 in SEQ ID NO: 3, 4 or 5 is Arg or Lys, preferably Arg, respectively.

[0021] Genogroup I VP1 proteins according to the invention, such as those defined above, may be of any one or more of the following genotypes: I.1, I.2, I.3, I.4, I.5, I.6, I.7, I.8, or I.9. Genotypes I.1 and I.4 are preferred.

[0022] SEQ ID NOS: 1-21 are also referred to herein as "reference sequences." A "segment" or "portion" of an amino acid sequence is a subsequence (or fragment) of contiguous amino acid residues of any given number of amino acid residues of the referenced amino acid sequence. The length of an amino acid sequence is measured by the number of amino acid residues it comprises, including the terminal residues. Amino acid sequence identity may be confirmed using protein sequence search and alignment programs freely accessible from the internet, such as PROTEIN BLAST (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi?PAGE=Proteins) and ExPASy (http: / / web.expasy.org / sim / ). A comprehensive list of sequence alignment tools can be found at http: / / molbiol-tools.ca / Alignments.htm.

[0023] The VP1 protein of a NoV of the present invention may be a VP1 protein of any genotype of NoV genogroup I, a fragment of such a protein, a derivative of said protein or said fragment, or a protein comprising the amino acid sequence of a VP1 protein or derivative of a genogroup I NoV, as defined above.

[0024] The VP1 protein may have amino acid deletions, substitutions, additions, or insertions compared to the reference sequence, as indicated above. Among these, deletions, substitutions, and additions are preferred. The number of such modifications indicated above refers to the total of all deletions, substitutions, additions, and insertions. The term "insertion" refers to an insertion within the amino acid sequence of the reference sequence, i.e., excluding additions at the C- or N-terminal ends. The term "addition" refers to an addition at the C- and / or N-terminal ends of the amino acid sequence of the reference sequence. Deletions may be deletions of amino acid residues at the end or within the reference sequence.

[0025] The VP1 proteins of the present invention may have the length of a naturally occurring genogroup I VP1 protein, or may be a fragment or derivative thereof. However, the VP1 proteins of the present invention must be capable of associating to form VLPs. Here, the VP1 proteins of the present invention preferably have a minimum length of 500 amino acid residues, as indicated above, and have minimal identity or similarity to a naturally occurring genogroup I VP1 protein, as also indicated above. Whether VLPs are formed can be determined by established methods such as electron microscopy (Laue M & Bannert N., 2010, J Applied Microbiol., 109:1159-1168; Harris JR, 1999, Methods Mol Biol., 117:13-30; Pogan R et al., 2018, J Phys.:Condens.Matter, 30:064006) or size exclusion chromatography (Effio CL et al., 2016, Vaccine, 34:1259-1267).

[0026] The present invention also provides nucleic acid molecules encoding the capsid proteins of the present invention. The nucleic acid molecules may be vectors used to express the proteins of the present invention in host cells or host organisms. The nucleic acid molecules may contain nucleic acid constructs containing nucleotide sequences encoding the proteins of the present invention, and the nucleic acid molecules may further contain genetic elements for expressing the nucleotide sequences. Further information about nucleic acid molecules and constructs is provided below in the section on producing the proteins of the present invention.

[0027] Virus-like particles (VLPs) of the present invention The present invention also provides VLPs consisting of or comprising the VP1 capsid protein of the present invention. VLPs are particles consisting of viral structural proteins but do not contain viral nucleic acid. Preferably, VLPs are particles consisting of viral structural proteins but do not contain Norovirus nucleic acid encoding VP1 or VP1 and VP2 of said VLP. In the case of Norovirus, VLPs consist of the structural protein VP1 or VP1 and VP2 proteins (or any fragment or derivative described herein). VLPs of the present invention comprise or consist of the VP1 capsid protein of the present invention, such as those defined in any one of items (i) to (iii), items (i') to (iii'), items (i'') to (iii''), or items (i''') to (iii''') above. These proteins are preferably capable of forming VLPs.

[0028] Preferably, a VLP of the present invention comprises at least 60, preferably at least 90, and more preferably about 180 VP1 protein molecules. It is not necessary for all VP1 protein molecules in a VLP of the present invention to be genogroup I VP1 capsid protein molecules of the present invention. A VLP may also contain other VP1 protein molecules, preferably genogroup I VP1 protein molecules. However, to confer a high stabilizing effect of the VP1 protein of the present invention on a VLP, at least 50%, preferably at least 70%, and more preferably at least 90% of the VP1 protein molecules in a VLP must be VP1 capsid protein molecules of the present invention. In a preferred embodiment, all VP1 protein molecules in a VLP are VP1 capsid protein molecules of the present invention. Thus, in one embodiment, a VLP of the present invention comprises at least 60, preferably at least 90, and more preferably about 180 VP1 capsid protein molecules of the present invention. A VLP may further comprise one or more VP2 protein molecules, preferably genogroup I VP2 protein molecules.

[0029] The VP1 capsid protein of the invention can spontaneously assemble into the VLPs of the invention. Expression and production of the VP1 protein of the invention and generation of VLPs are further described below.

[0030] The present invention also provides a method for enhancing the stability of NoV genogroup I VLPs, comprising replacing His residues in the sequence stretch Ala-Ala-Leu-Leu / Val-His-Tyr (SEQ ID NO: 57) in the P domain of the genogroup I VP1 capsid protein with Arg or Lys. The replacement is generally performed by appropriate alterations in a nucleic acid encoding the genogroup I VP1 protein and expressing the nucleic acid encoding the modified VP1 in a suitable expression host (described further below). The expressed VP1 protein is preferably allowed to assemble into a VLP of the invention in the presence or absence of additional genogroup I VP1 proteins of the same or different genogroup I genotype.

[0031] Immunogenic compositions of the present invention The present invention further provides immunogenic compositions comprising one or more NoV antigens, wherein at least one NoV antigen is a genogroup I VP1 capsid protein of the present invention. Accordingly, the VP1 capsid protein of the present invention is also referred to herein as an "antigen of the present invention." The immunogenic composition is capable of generating an immune response in a mammal against one or more NoV antigens in the composition. The immunogenic composition comprises a VP1 capsid protein of the present invention, or preferably, a VLP of the present invention, as a NoV antigen. The immunogenic composition may further comprise a pharmaceutically acceptable carrier and / or a vaccine adjuvant.

[0032] To simultaneously generate an immune response in a subject against multiple NoV antigens, e.g., two, three, or four different NoV antigens, the immunogenic composition may contain two or more different NoV antigens, e.g., two or more VP1 proteins. The NoV antigens used in the immunogenic compositions of the present invention depend on the NoV or NoVs to be immunized in the subject using the vaccine of the present invention. Because noroviruses (NoVs) that cause infection in mammals evolve, the antigens used in the immunogenic compositions may be modified or adapted to generate an immune response in mammals against NoVs that are considered health risks at a particular time or in a particular season. The immunogenic compositions of the present invention contain at least the VP1 capsid or VLP of the present invention. Thus, they contain at least a NoV genogroup I antigen. The immunogenic composition may also contain a second, i.e., additional, NoV genogroup I VP1 antigen of the present invention, which may or may not be a genogroup I VP1 antigen of the present invention; preferably, the additional NoV genogroup I antigen is also a genogroup I VP1 antigen of the present invention. Thus, in one embodiment, the immunogenic composition comprises two or more genogroup I VP1 antigens, preferably two or more genogroup I VP1 antigens of different genotypes, wherein the two or more genogroup I VP1 antigens are genogroup I VP1 antigens of the present invention.

[0033] The immunogenic composition may further comprise a NoV antigen from NoV genogroup GII and / or GIV. Preferably, the immunogenic composition additionally comprises a NoV antigen from NoV genogroup II (GII). The NoV antigen from genogroup GII and / or GIV is preferably the VP1 capsid protein.

[0034] The VP1 capsid proteins of genogroup GII and / or GIV that may be included in the immunogenic composition may be as follows: (a) the amino acid sequence of the protein consists of or comprises at least 500 contiguous amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 22 to 53, or (b) the amino acid sequence of the protein consists of or comprises at least 500 amino acid residues and has at least 80%, preferably at least 85%, more preferably at least 90% sequence identity over this length to a sequence segment of at least 500 contiguous amino acid residues consisting of the amino acid sequence of any one of SEQ ID NOs: 22 to 53, or (c) The amino acid sequence of the protein has 1 to 50, preferably 1 to 40, and more preferably 1 to 30 deletions, substitutions, additions, or insertions compared to a sequence segment of at least 500 contiguous amino acid residues consisting of any one of the amino acid sequences of SEQ ID NOs: 22 to 53.

[0035] Other embodiments of the VP1 capsid protein of genogroup II or IV antigens are as follows: (a') the amino acid sequence of the protein consists of or includes any one of the amino acid sequences of SEQ ID NOs: 22 to 53, or (b') the amino acid sequence of the protein has at least 80%, preferably at least 85%, more preferably at least 90%, and most preferably at least 95% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 22 to 53; or (c') The amino acid sequence of the protein has 1 to 50, preferably 1 to 40, more preferably 1 to 30, and even more preferably 1 to 20 deletions, substitutions, additions, or insertions compared to the amino acid sequence of any one of SEQ ID NOs: 22 to 53.

[0036] These GII or GII capsid protein genotypes are shown in the section on amino acid sequences.

[0037] There are no particular limitations regarding the genotype of the NoV antigen used in the immunogenic compositions of the present invention. Preferred genogroup I genotypes are any of the genogroup I genotypes listed above, preferably genotypes I.1 and I.4, and most preferably genotype I.4. Genogroup II antigens may be any one or more of the following genotypes: II.1, II.2, II.3, II.4, II.5, II.6, II.7, II.8, II.12, II.13, II.14, II.17, II.21, II.22, II.24, or II.25, preferably II.4 and II.17, and more preferably II.4. Genogroup IV antigens may be any one or more of the following genotypes: IV.1 or IV.3. As with genogroup I antigens, antigens from other genogroups are preferably VP1 proteins.

[0038] With regard to embodiments in which antigens from NoV genogroup I are combined with antigens from NoV genogroup II, the following examples of immunogenic compositions may be mentioned: those containing genotype I.1 antigens and genotype II.1 antigens; those containing genotype I.1 antigens and genotype II.4 antigens; those containing genotype I.1 antigens and genotype II.6 antigens; those containing genotype I.4 antigens and genotype II.1 antigens; those containing genotype I.4 antigens and genotype II.4 antigens; those containing genotype I.4 antigens and genotype II.17 antigens; those containing genotype I.4 antigens and genotype II.2 antigens; those containing genotype I.1 antigens and genotype II.17 antigens; those containing genotype I.1 antigens and genotype II.2 antigens; and those containing genotype I.4 antigens and genotype II.6 antigens; In all of these immunogenic composition embodiments, the composition contains at least the VP1 capsid protein of the invention as the genogroup I antigen, and preferably the genogroup I antigen is the VP1 capsid protein of the invention. Genogroup I and II antigens may be those defined above with reference to SEQ ID NOs. Preferred embodiments are those in which the immunogenic composition contains an antigen of genotype I.1 or I.4 (GI.4) and an antigen of genotype II.4 (GII.4) or GII.17 (GII.17). More preferred are those in which the immunogenic composition contains an antigen of genotype I.1 or I.4 and an antigen of genotype II.4. In all of these embodiments, the immunogenic composition may further contain a pharmaceutically acceptable carrier or vaccine adjuvant, as further described below.

[0039] In further embodiments, the immunogenic composition may comprise two or more antigens from a single NoV genogroup, preferably genogroup II. The immunogenic composition may comprise, in addition to the genotype IVP1 capsid protein of the present invention, two different antigens of genogroup II norovirus, e.g., an antigen of a first genotype of genogroup II norovirus and an antigen of a second genotype of genogroup II norovirus. For example, the composition may comprise an antigen of genotype II.1 NoV (e.g., the VP1 protein) and an antigen of genotype II.4 NoV (e.g., the VP1 protein). Alternatively, the composition may comprise an antigen of genotype II.1 NoV (e.g., the VP1 protein) and an antigen of genotype II.17 NoV (e.g., the VP1 protein). Alternatively, the composition may comprise an antigen of genotype II.4 NoV (e.g., the VP1 protein) and an antigen of genotype II.17 NoV (e.g., the VP1 protein). These genogroup II antigens may be as defined above with reference to SEQ ID NOs.

[0040] Derivatives of the antigens defined above are considered to be antigens of the genogroup and / or genotype to which the native antigen belongs. If an antigen, such as the VP1 protein, can belong to two different genogroups or genotypes using this rule, the antigen or derivative will belong to the genogroup or genotype that is most similar in terms of amino acid sequence identity to the full-length amino acid sequence of the native VP1 protein, such as any one of SEQ ID NOS: 1-56.

[0041] The immunogenic composition of the present invention preferably contains an antigen in the form of a NoV VLP. Thus, the immunogenic composition of this embodiment may contain the VLP of the present invention as defined above. The immunogenic composition preferably contains the VLP of the present invention and a NoV VLP of a genogroup II and / or genogroup IV antigen, preferably a NoV VLP of a genogroup II antigen. The VLP of a genogroup II and / or genogroup IV antigen preferably contains the VP1 protein mentioned above and the VP1 protein of the genotype mentioned above.

[0042] The immunogenic compositions of the invention may contain VLPs comprising or consisting of NoV antigens of genogroup I (containing the VP1 capsid protein of the invention) and VLPs comprising or consisting of NoV antigens of a second genogroup (e.g., genogroup II). The following immunogenic compositions may be mentioned by way of example: A composition comprising a VLP consisting of or comprising an antigen of genotype I.1 and a VLP consisting of or comprising an antigen of genotype II.1; a composition comprising a VLP consisting of or comprising an antigen of genotype I.1 and a VLP consisting of or comprising an antigen of genotype II.4; a composition comprising a VLP consisting of or comprising an antigen of genotype I.1 and a VLP consisting of or comprising an antigen of genotype II.6; a composition comprising a VLP consisting of or comprising an antigen of genotype I.1 and a VLP consisting of or comprising an antigen of genotype II.2; A composition comprising a VLP consisting of or comprising an antigen of genotype I.1 and a VLP consisting of or comprising an antigen of genotype II.17; a composition comprising a VLP consisting of or comprising an antigen of genotype I.4 and a VLP consisting of or comprising an antigen of genotype II.1; VLPs consisting of or comprising antigens of genotype I.4 and compositions comprising VLPs consisting of or comprising antigens of genotype II.4, and A composition comprising a VLP consisting of or comprising an antigen of genotype I.4 and a VLP consisting of or comprising an antigen of genotype II.6. A composition comprising a VLP consisting of or comprising an antigen of genotype I.4 and a VLP consisting of or comprising an antigen of genotype II.2; A composition comprising a VLP consisting of or comprising an antigen of genotype I.4 and a VLP consisting of or comprising an antigen of genotype II.17. In all these embodiments, the VLP consisting of or comprising an antigen of genotype I is a VLP of the invention, wherein 100% of the VP1 protein molecules of said VLP may be a VP1 capsid protein of the invention.

[0043] The immunogenic compositions of the present invention may comprise a genogroup I norovirus antigen (preferably the VP1 protein) and a genogroup II norovirus antigen (also preferably the VP1 protein) at a mass ratio ranging from 1:1 to 1:6, preferably from 1:1.5 to 1:5, and more preferably from 1:2 to 1:4. In another embodiment, the immunogenic compositions of the present invention comprise a genogroup I norovirus antigen and a genogroup II norovirus antigen at a mass ratio ranging from 5:1 to 1:5, preferably from 3:1 to 1:3, more preferably from 2:1 to 1:2, and even more preferably from 1.5:1 to 1:1.5.

[0044] In a preferred embodiment, the immunogenic composition of the present invention comprises the genogroup I VP1 capsid protein of the present invention and the genogroup II norovirus antigen (preferably the VP1 protein) in a mass ratio ranging from 5:1 to 1:5, preferably 3:1 to 1:3, more preferably 2:1 to 1:2, and even more preferably 1.5:1 to 1:1.5.

[0045] In a further preferred embodiment, the immunogenic composition of the present invention comprises a VLP of the present invention and a VLP of NoV genogroup II at a mass ratio ranging from 5:1 to 1:5, preferably 3:1 to 1:3, more preferably 2:1 to 1:2, and even more preferably 1.5:1 to 1:1.5. The VLPs of the present invention are as defined above. The mass ratio may be measured, for example, by subjecting the VLPs to SDS-PAGE, staining them, and reading the staining intensity using a commercially available reader. This measurement may be performed before mixing the VLPs, or after mixing the desired VLPs at the desired ratio. Alternatively, VLPs may be quantified using mass spectrometry such as MALDI-TOF.

[0046] The immunogenic composition may further contain a suitable carrier in a desired amount and mixing ratio. In the case of an aqueous liquid composition, a suitable carrier may be water or an aqueous solution having an appropriate pH, for example, 6 to 8, preferably 6.7 to 7.5. In addition to water, the aqueous solution may contain a buffer, an isotonicity agent, and / or a preservative, as necessary. In the case of a solid composition, the liquid composition may be dried or lyophilized.

[0047] Examples of buffers are phosphate buffer, Tris buffer, acetate buffer, and citrate buffer. Examples of possible tonicity agents are sodium chloride, sucrose, glycerol, and trehalose. An example of a possible preservative is thimerosal. However, the immunogenic composition may be provided sterilized without the addition of preservatives.

[0048] The composition may be liquid or solid. If liquid, it may be an aqueous solution or aqueous buffer. If solid, it may be a mixture containing NoV genogroup I capsid proteins, preferably a mixture containing NoV VLPs of the present invention. A preferred solid form is a lyophilized form.

[0049] An immunogenic composition is immunogenic in that, when administered to a subject, such as a human, it generates an immune response against the antigen contained therein. To aid in the immune response in a subject, the composition may contain a vaccine adjuvant. An example of an adjuvant is aluminum hydroxide (alum) or other aluminum salts, which are commonly known adjuvants for vaccines. However, in one embodiment, the immunogenic composition (and vaccine) does not contain an adjuvant. In a preferred embodiment, the composition (and vaccine) does not contain alum or another aluminum salt as an adjuvant.

[0050] When preparing the immunogenic compositions of the present invention, one or more antigens, preferably in the form of VLPs, may be mixed in or with a suitable carrier or vehicle. The carrier or vehicle may be an aqueous medium such as water or a solution. The aqueous medium may contain a buffer to adjust the pH, saline, and / or other additives. Possible additives include, but are not limited to, sucrose, glycerol, and trehalose. The NoV antigen may be stored in the aqueous medium until the immunogenic compositions or vaccines of the present invention are prepared. For long-term storage, it may be frozen or lyophilized. After preparation of the immunogenic composition, it may be sterilized and stored, for example, by sterile filtration. It may be stored in liquid form or frozen. It may also be stored as a dry powder after lyophilization.

[0051] Freeze-drying of immunogenic compositions and vaccines is well known in the art. Typically, compositions are freeze-dried in the presence of agents to protect the antigens and / or adjuvants of the present invention during the freeze-drying process and to obtain powders with desirable properties. Sugars such as sucrose, mannitol, trehalose, or lactose (present at an initial concentration of 10-200 mg / mL) are typically used for cryoprotection and lyophilization of protein antigens and to obtain freeze-dried cakes or powders with desirable properties. Freeze-dried compositions may be more stable. Other drying techniques, such as spray drying or spray freeze drying, may also be used.

[0052] The vaccine of the present invention Vaccines of the present invention comprise the immunogenic composition of the present invention in a form suitable for administration to a subject, or in a form that can be readily converted prior to administration into a form suitable for administration to a subject. Preferably, the vaccine contains the immunogenic composition in a dosage form suitable for administration as a single or unit dose, preferably containing an amount of antigen to be administered to a subject in a single dose.

[0053] The form suitable for administration is related to the mode of administration. For example, the vaccine may be a solid formulation that can be reconstituted before administration by adding a predetermined amount of water or an aqueous solution, suspension, or emulsion. In this way, a solution for administration, for example, by injection, can be prepared immediately before administration. Alternatively, the vaccine may be a solid formulation for intranasal administration to a subject. Furthermore, the vaccine may be a liquid preparation, preferably an aqueous liquid formulation, for administration by injection. In the latter case, the vaccine may be an aqueous solution in a unit dosage form.

[0054] In addition to the immunogenic composition, the vaccine may contain one or more pharmaceutical additives or carriers. The additives may be liquid or solid. Liquid additives include, but are not limited to, water, alcohol, saline, and buffer solutions. Other possible additives include, but are not limited to, preservatives and other additives such as antimicrobial agents, antioxidants, chelating agents, buffer substances, etc. The immunogenic composition of the present invention may itself be a vaccine within the meaning of the present invention.

[0055] The vaccine is an anti-NoV vaccine. It is also a pharmaceutical composition. Vaccines are generally used to prevent or treat NoV infection or reduce the severity of NoV infection in a subject. The present invention also provides methods for preventing or treating Norovirus infection or reducing the severity of NoV infection, generally comprising administering the immunogenic composition or vaccine of the present invention to a subject. The subject in which NoV can be prevented or treated, or the severity of NoV infection can be reduced, is a mammal, preferably a human. Both children and adults may be subjects for preventing or treating NoV infection. Children are preferred among humans because immunization is achieved early in life. Human subjects up to 16 years of age are considered children. Preferably, the NoV vaccine is used in children between the ages of 1 and 16, preferably between the ages of 2 and 14, and more preferably between the ages of 3 and 12.

[0056] The present invention is not limited by the route of administration of the vaccine. The vaccine of the present invention is preferably administered to a subject parenterally, for example, by injection. For administration by injection, the vaccine may be formulated as a liquid or as a solid to be reconstituted into a liquid form. Parenteral administration by injection may be intravenous, intradermal, intramuscular, or subcutaneous. Intradermal, intramuscular, or subcutaneous administration is preferred, with intradermal and intramuscular administration being more preferred. In one embodiment, the vaccine is administered intradermally. In another embodiment, the vaccine is administered intramuscularly. The vaccine may also be administered intranasally. In this case, the composition or vaccine may be a liquid, preferably an aqueous solution. Alternatively, the composition or vaccine for intranasal administration may be in a solid form, such as a lyophilized form.

[0057] When administering a vaccine to a human subject or in a method of the present invention, the NoV antigen is administered in an amount of 10 to 1000 μg, preferably 30 to 300 μg, and more preferably 55 to 150 μg. If the vaccine contains more than one NoV antigen, these amounts refer to the sum of the amounts of the individual NoV antigens. If the vaccine contains a genogroup I antigen and a genogroup II antigen, the amount of the genogroup II antigen may be the same as or higher than the amount of the genogroup I antigen. The amount of the genogroup II antigen may be 1.5 to 6 times, preferably 2.0 to 5 times, more preferably 2.5 to 4.5 times, and even more preferably 3.0 to 4.0 times the amount of the genogroup I antigen, by mass.

[0058] The vaccine may be packaged in a single-dose or multi-dose form in a container containing a desired amount of vaccine suitable for administration. Single-dose forms are preferred, and a single dose contains the NoV antigen in the dosage amounts described above. A single-dose form may contain 10-1000 μg, preferably 30-300 μg, and more preferably 55-150 μg of NoV antigen. When the vaccine contains a genogroup I antigen and a genogroup II antigen, the ratio of these antigens may be as defined in the previous paragraph.

[0059] The vaccine may be administered to a subject once or twice to enhance immunity against NoV infection. If the vaccine is administered twice, the second administration may be administered within 2 to 8 weeks, preferably within 3 to 5 weeks, after the first administration of the vaccine.

[0060] To confer immune protection not only against NoV but also against other viruses, the vaccines of the invention may also contain antigens against other infectious diseases, for example, to confer protection against NoV and rotavirus, the vaccine may include a rotavirus antigen.

[0061] The present invention also provides a method for producing an immunogenic composition or vaccine against NoV infection, comprising expressing a VP1 capsid protein of the present invention in an expression host, assembling the expressed VP1 capsid protein to form a VLP, and formulating the VLP for administration to a subject.

[0062] NoV antigen production The NoV antigens mentioned above can be expressed in and purified from different production hosts, including mammalian cells, insect cells, and plants or plant cells (for review: Herbst-Kralovetz, M., Mason, HS & Chen, Q. 2010, Exp. Rev. Vaccines, 9:299-307). Reliable purification protocols for NoV antigens and NoV VLPs, and their improved versions, have been described for insect cells using baculovirus expression systems (Jiang, X. et al., 1992, J. Virol., 66:6527-6532; Prasad BVV, Hardy D, Estes M. 2000, J. Infect. Dis., 181:S317-S321; Huhti, L. et al., 2010, Arch. Virol., 155:1855-1858; Koho, T. et al., 2012, J. Virol. Methods, 181:6-11; Huhti, L. et al., 2013, Arch. Virol., 158:933-942; WO2013192604) and for plants (Santi L. et al., 2008, Vaccine, 26:1846-1854; Lai, H. & Chen, Q. 2012, Plant Cell Rep., 31:573-584). EP2601970 can also be considered as being related to the production of NoV VLPs.

[0063] Although there are no differences in the structural and immunogenic properties of VLPs isolated from insect cells and plant cells, the preferred VLP production system is plant-based because it is possible to avoid the impurities of baculovirus in antigens or VLPs isolated from plant tissue. Furthermore, plant-based transient expression systems, unlike baculovirus, are easily scalable. NoV antigen genes can be successfully expressed in plants using a plant virus-based expression system called magnICON® (Gleba et al., 2005, Vaccine, 23:17-18; Marillonnet et al., 2005, Nat. Biotechnol., 23:718-723; Gleba et al., Curr. Opin. Biotechnol., 2007, 18:134-141; Klimyuk, V. et al., 2014, Curr. Top. Microbiol. Immunol., 375:127-154), which allows for the easy expression of viral VLPs in Nicotiana benthamiana plants (Zahin, M. et al., 2016, PLoS One, 11(8):e0160995).

[0064] More specifically, the capsid protein and other antigens of the present invention to be included in the immunogenic composition or vaccine can be produced by known methods of protein expression in standard expression systems. When producing a capsid protein or antigen, the nucleotide sequence encoding it can be expressed in a suitable host organism. Methods that can be used to produce and purify proteins of interest have been described in the prior art, and any of these methods can be used. When using a eukaryotic expression system, one or more introns can be inserted into the coding sequence of the antigen.

[0065] A particularly effective expression method is a plant expression system, which is also known in the prior art. A possible method for achieving the expression of a desired nucleotide sequence encoding an antigen according to the present invention in plants is to use a self-replicating (viral) replicon containing a nucleotide sequence encoding the antigen. Plant viral expression systems are described in many publications, such as WO2012019660, WO2008028661, WO2006003018, WO2005071090, WO2005049839, WO2006012906, WO02101006, WO2007137788, or WO02068664, and many more publications are cited in these documents. Various methods are known for introducing nucleic acid molecules, such as DNA molecules, into plants or plant parts for transient expression. Agrobacterium may be used to transfect plants with nucleic acid molecules (vectors) or nucleic acid constructs, for example by agroinfiltration or by spraying with a suspension of Agrobacterium. See WO2012019660, WO2014187571 or WO2013149726.

[0066] In embodiments where strong expression of an antigen is desired, a nucleic acid construct containing a nucleotide sequence encoding a capsid protein may encode a viral vector capable of replicating in plant cells to form a viral vector replicon. To replicate, the viral vector and replicon may contain an origin of replication that can be recognized by a nucleic acid polymerase present in plant cells, such as a viral polymerase expressed from the replicon. In the case of an RNA viral vector (referred to as an "RNA replicon"), the replicon can be formed from a DNA construct after the latter is introduced into the nucleus of the plant cell by transcription under the control of a promoter active in plant cells. In the case of a DNA replicon, the replicon can be formed by recombination between two recombination sites flanking the viral replicon-encoding sequence in the DNA construct, as described, for example, in WO 00 / 17365 and WO 99 / 22003. When the replicon is encoded by a DNA construct, an RNA replicon is preferred. The use of DNA and RNA viral vectors (DNA or RNA replicons) has been widely described in the literature for many years. Some examples are the following patent publications: WO2008028661, WO2007137788, WO2006003018, WO2005071090, WO2005049839, WO02097080, WO02088369, and WO02068664. Examples of DNA viral vectors include those based on geminiviruses. In the present invention, plant RNA virus-based viral vectors or replicons, particularly those based on single-stranded positive-strand RNA viruses, are preferably used. Thus, the viral replicon may be a single-stranded positive-strand RNA replicon. Examples of such viral vectors include those based on tobacco mosaic virus (TMV) and portex virus X (PVX). By "based," we mean that the viral vector uses the replication systems, such as replicase and / or other proteins, involved in the replication of these viruses. Portexvirus-based viral vectors and expression systems are described in EP2061890 or WO2008 / 028661.

[0067] The capsid protein may be expressed in a multicellular plant or a portion thereof, particularly in a higher plant or a portion thereof. Both monocotyledonous and dicotyledonous (crop) plants can be used. Common plants that can be used to express the protein include Nicotiana tabacum and Nicotiana benthamiana. However, many others can be used as well.

[0068] Generally, capsid proteins can be expressed in the cytosol of cells of a plant or part of a plant. In this case, a signal peptide that directs the target protein to a specific compartment is not added to the enzyme. Alternatively, the capsid protein or antigen can be expressed in or targeted to the chloroplast of a plant, or secreted into the extracellular space. In these cases, an N-terminal presequence, such as a plastid transit peptide or a signal sequence that targets the extracellular space, is added to the N- or C-terminal end, preferably the C-terminal end, of the capsid protein as the target protein.

[0069] The next step is to recover plant material containing the expressed capsid protein from the antigen-expressing plant. The plant material may be, for example, leaves, roots, tubers, or seeds, or crushed, milled, or powdered leaf, root, tuber, or seed products. The capsid protein may then be extracted from the plant material using an aqueous buffer. This may involve homogenizing the plant material, and insoluble material may be removed by centrifugation or filtration. To produce an aqueous buffer solution of the capsid protein, the soluble components, including the capsid protein, are extracted into the aqueous buffer. The aqueous buffer may contain an inorganic or organic acid or a salt thereof and may have a pH as defined below for aqueous solutions of the present invention. Additionally, the aqueous buffer may contain salts and / or sulfhydryl compounds. The capsid protein in the obtained antigen preparation may then be further purified using standard protein purification methods, such as chromatography.

[0070] NoV VP1 protein or its derivative capsid protein can form VLPs. These VLPs usually form spontaneously in the aqueous buffer used in extraction and purification. The formation of VLPs can be confirmed, for example, by electron microscopy.

[0071] When the immunogenic composition or vaccine of the present invention contains two or more NoV antigens, the two or more antigens may be expressed and purified separately and then mixed in the desired ratio when preparing the composition or vaccine. Two or more capsid proteins or antigens may also be co-expressed in the same plant cell or plant and purified together as a mixture.

[0072] Construct engineering for the expression of antigens, including the VP1 antigen, and antigen expression and purification are described in Examples 1 and 2. Figure 6 shows the construction of an expression vector containing the coding sequence for the GI.4 antigen. A similar approach using type IIS restriction enzymes can be used to clone any sequence of interest into the expression vector. Figure 7 shows wild-type and mutant GI.4 VP1 protein expression on a Coomassie-stained gel. [Example]

[0073] Example 1 Construction and functional testing of expression vectors for norovirus VP1 wild-type and mutant versions A sequence corresponding to the VP1 capsid protein of norovirus GI.4 Chiba 407 (Japan, 1987) (GenBank accession no.: BAB18267, 544 amino acid residues, SEQ ID NO: 1, FIG. 1) was generated using gene synthesis, and flanking type IIS restriction enzyme BsaI sites were added for cloning. Norovirus GI.4 Chiba 407 modules were cloned into a TMV-based viral expression vector (magnICON® system, see below) using the type IIS restriction enzyme BsaI, which creates different, customized overhangs for each module, allowing for assembly of the final construct by removal of these restriction enzyme recognition sites (Engler, C., Kandzia, R. & Marillonnet, S. 2008, PLoS One, 3:e3647).

[0074] Analysis of the VP1 protein of GI.4 Chiba 407 revealed that the wild-type protein sequence lacks two methionine residues at the N-terminus and two arginine residues at the C-terminus, resulting in a discrepancy between the theoretical and measured protein masses. Therefore, to obtain a mutant with a consistent theoretical and measured mass, we created an N- and C-terminal truncated NC mutant (SEQ ID NO: 2) of GI.4 Chiba 407 VP1 lacking the two methionine residues at the N-terminus and the two arginine residues at the C-terminus. Each norovirus GI.4 Chiba 407 VP1 module was generated using PCR with flanking type IIS restriction enzyme BsaI sites and cloned into a TMV-based magnICON® viral expression vector using these BsaI sites. The NC version of SEQ ID NO: 2 (compared to the wild-type sequence: ΔMM at the N-terminus and ΔRR at the C-terminus) served as a basis for introducing additional mutations.

[0075] GI.4 VLPs exhibited lower homogeneity and stability compared with GII.4 VLPs. Furthermore, in the case of GI.4 Chiba 407 wild-type and NC versions of VP1, antigen-associated high-molecular-weight products were reproducibly co-purified and co-formulated with VLPs. This behavior was not observed in the GII.4 strain, so comparative sequence and structural analysis was performed. A single arginine amino acid residue was identified within a conserved but structurally flexible region of the P1 domain of genogroups II and IV strains, which may provide a salt bridge between the shell and protruding domains to improve VP1 conformation, multimerization, and assembly, thereby stabilizing the resulting VLPs. In genogroup I strains, the amino acid residue at this position is histidine. Therefore, this histidine residue in the VP1 sequence of GI.4 Chiba 407 was replaced with arginine (H474R in the wild-type and H472R for the NC mutant). Each norovirus GI.4 Chiba 407 VP1 NC version module was generated using PCR with flanking type IIS restriction enzyme BsaI sites and cloned into a TMV-based magnICON® viral expression vector using these BsaI sites, resulting in the NCHR version of GI.4 Chiba 407 VP1 (SEQ ID NO: 3) (compared to the wild-type sequence: ΔMM at the N-terminus, H474R, ΔRR at the C-terminus).

[0076] To further improve the stability and integrity of GI.4 Chiba 407 VLPs, the internal shell domain was modified with residue substitutions that allowed additional shell-stabilizing salt bridges to form on the internal surface of the VLP (i.e., the N-terminal STALATA motif was modified to SKALADA or SDALAKA). The NCHRKD (SEQ ID NO: 4) and NCHRDK (SEQ ID NO: 5) versions of each norovirus GI.4 Chiba 407 VP1 were generated using PCR with flanking type IIS restriction enzyme BsaI sites and cloned into a TMV-based magnICON® viral expression vector, resulting in the NCHRKD (SEQ ID NO: 4) and NCHRDK (SEQ ID NO: 5) versions of GI.4 Chiba 407 VP1 (compared to the wild-type sequence: ΔMM, T41K / D, T45D / K, H474R at the N-terminus, and ΔRR at the C-terminus).

[0077] Based on the magnICON® technology (Gleba, Y., Klimyuk, V. & Marillonnet, S., 2005, Vaccine, 2005, 23:2042-2048; Gleba, Y., Klimyuk, V. & Marillonnet, S. 2007, Curr. Opin. Biotechnol., 18:134-141), two closely related plant viruses from the genus Tobamovirus (tobacco mosaic virus, TMV), namely TVCV (turnip vein clearing virus); Lartey, R.T., Lane, L.C. & Melcher, U. 1994, Arch. Virol., 138:287-298; Lartey, R.T., Voss, T.C. & Elements from Melcher, U. 1995, Gene, 166:331-332) and crTMV (a crucifer-infecting tobamovirus; Dorokhov, YL, Ivanov, PA, Novikov, VK, et al. 1994, FEBS Lett., 350:5-8) were used to develop viral binary expression vectors. The resulting vectors are called "TMV-based" because the parent viruses are members of the Tobamovirus genus and are related to the well-known tobacco mosaic virus (TMV). All three viruses (TVCV, crTMV, and TMV) are positive-strand RNA viruses and share the same overall structure and replication mode. Essentially, the viruses encode an RNA-dependent RNA polymerase (RdRP), a movement protein (MP), and a coat protein (CP). The RdRP replicates the complete viral RNA transcript (genomic RNA) as well as two subgenomic RNAs (sgRNAs) required for expression of two other viral proteins, MP and CP. MP is required for short-distance cell-to-cell movement of viral genomic RNA within infiltrated leaves. CP is required for viral particle formation and long-distance systemic movement from leaf to leaf via the vascular system. Viral particle formation is not required for cell-to-cell movement. Therefore, the CP was deleted from the viral vector and replaced with the gene of interest.Therefore, viral vectors cannot produce viral particles and express the target gene at a higher level. In addition to the viral protein gene and the target gene, viral vectors also contain 5' and 3' untranslated (5'ntr and 3'ntr) viral sequences that are essential for replication (Marillonnet, S., Giritch, A., Gils, M. et al., 2004, Proc. Natl. Acad. Sci. USA, 101:6852-7).

[0078] To efficiently express TMV-based viral vectors in plant cells, we cloned the viral vector cDNA between a plant promoter and a plant terminator (Act2 and nos) (Marillonnet, S., Giritch, A., Gils, M. et al., 2004, Proc. Natl. Acad. Sci. USA., 101:6852-6857), and added plant introns within the RdRP and MP sequences (Marillonnet, S., Thoeringer, C., Kandzia, R. et al., 2005, Nat. Biotechnol., 23:718-723). To efficiently deliver TMV-based viral vectors into plant cells, we used Agrobacterium tumefaciens. Therefore, the complete viral vector (a plant promoter, a TMV-based viral vector sequence carrying the gene of interest, and a plant terminator) was cloned between the left and right border regions of the T-DNA of the binary vector. The elements of a binary vector are the pVS1 origin for plasmid replication in Agrobacterium (Hajdukiewicz, P., Svab, Z. & Maliga, P., 1994, Plant Mol. Biol., 25:989-994), the co / E1 origin for plasmid replication in Escherichia coli, the nptIII kanamycin antibiotic resistance gene (Frisch, DA, Harris-Haller, LW, Yokubaitis, NT et al., 1995, Plant Mol. Biol., 27:405-409), and the T-DNA left and right borders to demarcate the ends of the DNA to be transferred into the plant cell (Frisch, DA, Harris-Haller, LW, Yokubaitis, NT et al., 1995, Plant Mol. Biol., 27:405-409). A lacZα cassette amplified from pUC19 to facilitate blue-white selection was inserted between two BsaI restriction enzyme recognition sites, allowing seamless in-frame cloning of the gene of interest.Therefore, during the initial construction of the viral vector, all naturally occurring BsaI recognition sites were removed to allow for easy and robust cloning of the gene of interest.

[0079] For functional testing of recombinant protein expression, selected Agrobacterium strains carrying TMV-based expression vectors were cultured in liquid LBS medium in which tryptone was replaced with soybean peptone (Duchefa Biochemie, Haarlem, The Netherlands) and supplemented with 50 mg / mL rifampicin and 50 mg / mL kanamycin. Agrobacterium cultures were grown at 28°C until an OD600 of 2 to 4 was reached. Infiltration solutions were prepared by culturing Agrobacterium cultures in infiltration buffer (10 mM MES, pH 5.5, 10 mM MgSO4) to a defined cell density (OD 600 The culture is prepared by diluting the culture to a concentration of 0.1% (corresponding to a 1000-fold dilution of a culture with a pH of 2.0).

[0080] Leaves of Nicotiana benthamiana plants grown under controlled and standardized conditions for 6–8 weeks were infiltrated with the Agrobacterium infiltration solution using a needleless syringe and then placed in a greenhouse for approximately 7 days for recombinant protein expression and accumulation. The plant leaf material was then harvested, ground into a fine powder in liquid nitrogen, and proteins were extracted using Laemmli buffer. Protein extracts were analyzed by SDS-polyacrylamide gel electrophoresis and proteins visualized by Coomassie staining.

[0081] Example 2 Purification of norovirus VLPs from plant material Norovirus VP1 VLPs were purified as described below, allowing for the facile expression of viral VLPs in Nicotiana benthamiana plants (Zahin, M. et al., 2016, PLoS One, 11(8):e0160995), Five-week-old Nicotiana benthamiana plants were vacuum-infiltrated (80-100 mbar for 3-4 min) with diluted Agrobacterium tumefaciens cultures harboring assembled TMV-based magnICON® vectors (Gleba et al., 2005, Vaccine, 23:17-18; Marillonnet et al., 2005, Nat. Biotechnol., 23:718-723; Gleba et al., Curr. Opin. Biotechnol., 2007, 18:134-141; Klimyuk, V. et al., 2014, Curr. Top. Microbiol. Immunol., 375:127-154). Plant material was harvested 6-14 days after infiltration. Harvesting at 7-8 days post-infiltration yields the highest expression levels.

[0082] The green biomass was homogenized in the presence of two volumes of neutral buffer (i.e., 15 g of biomass and 30 mL of 100 mM Tris, 5 mM NaSO, pH 7.5). For clarification, the plant homogenate was centrifuged at 15,000 × g for 20 min. The resulting extract was further clarified by filtration using Millipore® glass fiber filters (AP25).

[0083] High molecular weight components were sedimented by ultracentrifugation (150,000 × g for 90 minutes). The precipitate was suspended in 1 mL of 20 mM histidine, 137 mM NaCl, pH 6.0, and clarified by centrifugation at 15,000 × g for 20 minutes. The VLP-containing supernatant was placed on top of a 30% sucrose cushion (in 20 mM histidine, 137 mM NaCl, pH 6.5). Ultracentrifugation was carried out at 150,000 × g for 90 minutes. The resulting precipitate was resuspended in 20 mM histidine, 137 mM NaCl, pH 6.5.

[0084] Example 3 Characterization of purified VP1 VLPs Transmission electron microscope (TEM) The presence of assembled VLPs was monitored by transmission electron microscopy. TEM micrographs were taken to visualize the size, dispersity, and icosahedral morphology of the purified VLPs.

[0085] Samples were prepared using the single droplet negative staining method (J. Robbin Harris, Methods in Molecular Biology 117: Electron Microscopy Methods and Protocols, chapters S.13-30). Precoated grids (Formvar-Carbon, Cu 200 mesh, FCF200-Cu-25, Science Services GmbH, Munich, Germany) were used as support membranes, and UranyLess (E22409, Science Services GmbH, Munich, Germany) was used as contrast solution. 10 μl of each sample was added to the grid and incubated for 10 min. The grid surface was washed by placing the coated side on a droplet of ultrapure water for 5 s. Excess water was removed with filter paper. VLPs were stained twice with ready-to-use UranyLess for 1 min each time. After drying overnight, the grids were viewed using an EM900 transmission electron microscope (Carl Zeiss Microscopy, Oberkochen, Germany) operating at 80 kV. Micrographs were acquired using a Variospeed SSCCD camera SM-1k-120 (Trondle, Moorenweis, Germany) with iTEM imaging software (EMSIS GmbH, Muenster, Germany). [Ref.] J.Robbin Harris: Negative staining of thinly spread biological particulates, Methods in Molecular Biology 117: Electron Microscopy Methods and Protocols chapter S.13~30

[0086] Size-exclusion high-performance liquid chromatography (SE-HPLC) VLP formation, relative content and size (molar mass and radius) were confirmed by size-exclusion high-performance liquid chromatography (SE-HPLC) with ultraviolet (UV), light scattering (LS) and refractive index (RI) detection.

[0087] SE-HPLC analysis was performed on an Agilent 1200 Series HPLC system (Agilent Technologies Deutschland GmbH, Waldbronn, Germany). The HPLC consisted of a G1312A binary pump, a G1379B micro vacuum degasser, a G1329A automatic liquid sampler, a G1330B automatic liquid sampler thermostat, a G1316A thermostated column compartment, and a G1314C variable wavelength detector. A miniDAWN TREOS laser photometer and an Optilab rEX refractometer with a quasi-elastic dynamic light scattering (QELS-DLS) detector from Wyatt Technology Europe GmbH were connected in-line to the SE-HPLC system.

[0088] The maximum sample injection volume was 100 μl, and samples were thermostated at 23°C in the autosampler before injection. Runs were performed at 25°C and in triplicate. VLPs were separated using a TSKGel G6000 PWxl analytical column (300 × 7.8 mm, 13 μm particle size, >1000 Å pore size, Tosoh Bioscience, Stuttgart, Germany) with a TSKgel PWxl guard column (40 × 6 mm, 12 μm particle size, mixed pore size, Tosoh Bioscience) as the stationary phase, and 25 mM disodium hydrogen phosphate / 125 mM sodium chloride / 1 mM sodium chloride (pH 7.4) as the SE-HPLC eluent (mobile phase) at a flow rate of 0.8 ml / min.

[0089] Control of the SE-HPLC system and peak integration from the UV signal to determine VLP content were performed using ChemStation software (version B.04.03, Agilent). The downstream Wyatt detector array was controlled by the program ASTRA (version 5, Wyatt) and used to characterize VLPs by measuring their size using multi-angle light scattering (MALS), dynamic light scattering (DLS), and refractive index (RI) detection. Data analysis and calculation of VLP molar mass and radius were also performed using ASTRA program tools and models.

[0090] Capillary gel electrophoresis (CGE) To test the purity of VP1, CGE-on-a-chip analysis was performed on an Agilent 2100 Bioanalyzer (Agilent Technologies Deutschland GmbH; Waldbronn, Germany) using the Agilent Protein 230 kit (sizing range: 14–230 kDa) and 2100 Expert software (Kuschel, M. et al. 2002, J Biomol Tech 13(3):172–178). All reagents and chips were prepared according to the manufacturer's instructions. The gel-dye mixture for protein separation was pipetted into the designated reservoir on the chip and forced into the microfluidic channels using the chip priming station.

[0091] Four microliters of each VLP sample and 2 μl of sample buffer were mixed and heated at 95°C for 5 minutes. The sample buffer for reducing conditions contained lithium dodecyl sulfate, two internal standards, and 3.5% (v / v) 1 M DTT as a reducing agent. After adding 84 μl of water to each sample-buffer mixture, 6 μl of each sample was loaded onto the chip along with a protein ladder. Chip run results were displayed as gel-like images, electropherograms, and in tabular format. Baseline correction and peak integration of electropherogram peaks were performed automatically, with manual baseline correction of peaks performed on a case-by-case basis if necessary. Protein peaks for the desired product (intact VP1 coat protein) and product-related material (N-terminally truncated VP1) could be identified and were clearly distinguishable from product- or process-related impurities by comparing migration times in seconds or protein sizes in kDa, respectively. [Ref.] Kuschel, M., T. Neumann, et al. (2002). "Use of lab-on-a-chip technology for protein sizing and quantitation." J Biomol Tech 13(3):172~178.

[0092] result The H472R amino acid substitution significantly alters VLP assembly and improves VLP homogeneity. A single, highly homogeneous VLP product was detected in test batches produced on a pilot scale. SE-HPLC:Chi_NCHR showed much higher VLP content and purity (95.0%) compared to previous Chi and Chi_NC preparations (75-85%). CGE, reduction: Degradation of VP1 in Chi_NCHR remained at the same level (80–85%) compared to the Chi_NC preparation and showed no improvement. TEM: No significant changes, but perhaps the protruding domains of Chi_NCHR are more pronounced than those of Chi_NC-VLP or Chi-VLP.

[0093] Example 4 Relative immunogenicity of purified VP1 VLPs of GI.4 Chiba NC (wild-type) and GI.4 Chiba NCHR mutant versions in mice using the intramuscular (IM) delivery route. Recombinant norovirus VLPs were administered twice IM to BALB / C mice in PBS (pH 7.3) at weeks 0 and 3. Groups were immunized with GI.4 Chiba VLPs at a 10 μg VLP dose of either GI.4 Chiba NC (Group I) or GI.4 Chiba NCHR (Group II). All mice were terminated at week 5 of the study. Humoral (antibody) immune responses were analyzed by an ELISA-based assay.

[0094] Test animals BALB / c Ola / Hsd female mice (Envigo, Netherlands) were transported to the animal facility at room temperature. Animals were acclimatized for one week before immunization and were immunized at 7 weeks of age. A health monitoring data summary form was provided with the mice during transport. Animal health (clinical signs of illness) and welfare were monitored daily by animal facility staff. All procedures were approved, and all procedures were performed in accordance with the guidelines of the Finnish National Board of Animal Experimentation.

[0095] Immunization Procedure During immunization and related procedures, mice were anesthetized with inhaled isoflurane. At the beginning of the study, animals were weighed and marked by group tattoo and individual ear piercing. Test articles (50 μl volume) were administered IM into the caudal tentacle muscle using a 0.5 mL insulin syringe (29 G × ½”-0.33 × 12 mm).

[0096] Termination Procedures and Sampling Animal weights were recorded at termination. Mice were anesthetized with 1 mg / kg medetomidine (Dorbene® 1 mg / mL, Laboratorios Syva) and 75 mg / kg ketamine (Ketalar® 50 mg / mL, Pfizer) and terminated by terminal whole blood collection from the axillary (underarm) region. Serum was separated from each individually collected whole blood sample and stored at -20°C until use.

[0097] Humoral immune response assays Antigen-specific IgG titers in serum were tested by enzyme-linked immunosorbent assay (ELISA) as previously described (Blazevic et al., 2011, Vaccine, 29:812-8133; Tamminen et al., 2012, Immunology, 135:89-99). A porcine gastric mucin (PGM)-based homologous blocking assay (Lindesmith et al., 2012, J. Virol., 86:873-883) was used to determine the ability of immune sera to block binding of NoV VLPs to human histo-blood group antigens (HBGAs), the putative NoV receptors, as previously described (Uusi-Kerttula et al., 2014, Microbes Infect., 16:472-480).

[0098] When administered parenterally via the IM route at a dose of 10 μg, both GI.4 Chiba VLPs induced substantial genotype-specific serum IgG responses in BALB / c mice ( FIG. 11 ). No significant differences were observed between individual mice or between the two experimental groups ( FIG. 11 ). Furthermore, pooled sera from both groups immunized twice with 10 μg of GI.4 Chiba VLP had equally high blocking activity of homologous GI.4 Chiba VLP binding to the PGM HBGA receptor ( FIG. 11 ). In conclusion, no differences were observed in the immunogenicity of GI.4 Chiba NC (group I) or GI.4 Chiba NCHR (group II) VLPs when comparing the induced immune responses. <Sequence Listing> SEQUENCE LISTING <110> Icon Genetics GmbH <120> Norovirus-like particles with improved stability <130> PCT-17702 <160> 61 <170> PatentIn version 3.5 <210> 1 <211> 544 <212> PRT <213> Norovirus <400> 1 Met Met Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro 20 25 30 Ile Asp Pro Val Ala Gly Ser Ser Thr Ala Leu Ala Thr Ala Gly Gln 35 40 45 Val Asn Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Ala Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys 225 230 235 240 Tyr Leu Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu 245 250 255 Ser Pro Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Ile Asp Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu 275 280 285 Cys Lys Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu 290 295 300 Thr Glu Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro 305 310 315 320 Ala Gly Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser 325 330 335 Lys Ile Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser 340 345 350 Val Lys Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr 355 360 365 Leu Asp Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln 370 375 380 Trp Thr Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp 385 390 395 400 Lys Ile Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala 405 410 415 Pro Ala Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met 420 425 430 Ala Ser Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro 435 440 445 Cys Leu Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala 450 455 460 Pro Ile Gln Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 Asn Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr 485 490 495 Cys Val Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp 500 505 510 Gly Val Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val Arg Arg 530 535 540 <210> 2 <211> 540 <212> PRT <213> Norovirus <400> 2 Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr Gly Ala 1 5 10 15 Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro Ile Asp 20 25 30 Pro Val Ala Gly Ser Ser Thr Ala Leu Ala Thr Ala Gly Gln Val Asn 35 40 45 Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro Gln Gly 50 55 60 Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu Phe Asp 65 70 75 80 Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu Ser Gln 85 90 95 Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val Leu Ala 100 105 110 Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val Pro Pro 115 120 125 Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu Phe Pro 130 135 140 His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val Pro Leu 145 150 155 160 Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln Pro Thr 165 170 175 Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly Gly Ala 180 185 190 Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu Thr Cys 195 200 205 Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr Val Glu 210 215 220 Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys Tyr Leu 225 230 235 240 Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu Ser Pro 245 250 255 Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr Ile Asp 260 265 270 Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu Cys Lys 275 280 285 Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu Thr Glu 290 295 300 Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro Ala Gly 305 310 315 320 Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser Lys Ile 325 330 335 Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser Val Lys 340 345 350 Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr Leu Asp 355 360 365 Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln Trp Thr 370 375 380 Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp Lys Ile 385 390 395 400 Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala Pro Ala 405 410 415 Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met Ala Ser 420 425 430 Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro Cys Leu 435 440 445 Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala Pro Ile 450 455 460 Gln Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr Asn Arg 465 470 475 480 Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr Cys Val 485 490 495 Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp Gly Val 500 505 510 Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val 515 520 525 Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val 530 535 540 <210> 3 <211> 540 <212> PRT <213> artificial <220> <223> H472R MUTATION <400> 3 Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr Gly Ala 1 5 10 15 Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro Ile Asp 20 25 30 Pro Val Ala Gly Ser Ser Thr Ala Leu Ala Thr Ala Gly Gln Val Asn 35 40 45 Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro Gln Gly 50 55 60 Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu Phe Asp 65 70 75 80 Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu Ser Gln 85 90 95 Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val Leu Ala 100 105 110 Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val Pro Pro 115 120 125 Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu Phe Pro 130 135 140 His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val Pro Leu 145 150 155 160 Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln Pro Thr 165 170 175 Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly Gly Ala 180 185 190 Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu Thr Cys 195 200 205 Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr Val Glu 210 215 220 Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys Tyr Leu 225 230 235 240 Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu Ser Pro 245 250 255 Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr Ile Asp 260 265 270 Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu Cys Lys 275 280 285 Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu Thr Glu 290 295 300 Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro Ala Gly 305 310 315 320 Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser Lys Ile 325 330 335 Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser Val Lys 340 345 350 Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr Leu Asp 355 360 365 Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln Trp Thr 370 375 380 Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp Lys Ile 385 390 395 400 Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala Pro Ala 405 410 415 Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met Ala Ser 420 425 430 Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro Cys Leu 435 440 445 Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala Pro Ile 450 455 460 Gln Gly Glu Ala Ala Leu Leu Arg Tyr Val Asp Pro Asp Thr Asn Arg 465 470 475 480 Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr Cys Val 485 490 495 Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp Gly Val 500 505 510 Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val 515 520 525 Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val 530 535 540 <210> 4 <211> 540 <212> PRT <213> Artificial Sequence <220> <223> T39K, T43D, H472R MUTATIONS <400> 4 Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr Gly Ala 1 5 10 15 Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro Ile Asp 20 25 30 Pro Val Ala Gly Ser Ser Lys Ala Leu Ala Asp Ala Gly Gln Val Asn 35 40 45 Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro Gln Gly 50 55 60 Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu Phe Asp 65 70 75 80 Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu Ser Gln 85 90 95 Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val Leu Ala 100 105 110 Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val Pro Pro 115 120 125 Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu Phe Pro 130 135 140 His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val Pro Leu 145 150 155 160 Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln Pro Thr 165 170 175 Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly Gly Ala 180 185 190 Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu Thr Cys 195 200 205 Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr Val Glu 210 215 220 Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys Tyr Leu 225 230 235 240 Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu Ser Pro 245 250 255 Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr Ile Asp 260 265 270 Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu Cys Lys 275 280 285 Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu Thr Glu 290 295 300 Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro Ala Gly 305 310 315 320 Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser Lys Ile 325 330 335 Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser Val Lys 340 345 350 Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr Leu Asp 355 360 365 Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln Trp Thr 370 375 380 Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp Lys Ile 385 390 395 400 Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala Pro Ala 405 410 415 Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met Ala Ser 420 425 430 Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro Cys Leu 435 440 445 Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala Pro Ile 450 455 460 Gln Gly Glu Ala Ala Leu Leu Arg Tyr Val Asp Pro Asp Thr Asn Arg 465 470 475 480 Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr Cys Val 485 490 495 Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp Gly Val 500 505 510 Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val 515 520 525 Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val 530 535 540 <210> 5 <211> 540 <212> PRT <213> Artificial Sequence <220> <223> T39D, T43K, H472R MUTATIONS <400> 5 Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr Gly Ala 1 5 10 15 Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro Ile Asp 20 25 30 Pro Val Ala Gly Ser Ser Asp Ala Leu Ala Lys Ala Gly Gln Val Asn 35 40 45 Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro Gln Gly 50 55 60 Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu Phe Asp 65 70 75 80 Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu Ser Gln 85 90 95 Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val Leu Ala 100 105 110 Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val Pro Pro 115 120 125 Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu Phe Pro 130 135 140 His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val Pro Leu 145 150 155 160 Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln Pro Thr 165 170 175 Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly Gly Ala 180 185 190 Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu Thr Cys 195 200 205 Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr Val Glu 210 215 220 Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys Tyr Leu 225 230 235 240 Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu Ser Pro 245 250 255 Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr Ile Asp 260 265 270 Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu Cys Lys 275 280 285 Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu Thr Glu 290 295 300 Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro Ala Gly 305 310 315 320 Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser Lys Ile 325 330 335 Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser Val Lys 340 345 350 Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr Leu Asp 355 360 365 Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln Trp Thr 370 375 380 Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp Lys Ile 385 390 395 400 Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala Pro Ala 405 410 415 Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met Ala Ser 420 425 430 Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro Cys Leu 435 440 445 Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala Pro Ile 450 455 460 Gln Gly Glu Ala Ala Leu Leu Arg Tyr Val Asp Pro Asp Thr Asn Arg 465 470 475 480 Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr Cys Val 485 490 495 Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp Gly Val 500 505 510 Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val 515 520 525 Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val 530 535 540 <210> 6 <211> 539 <212> PRT <213> Norovirus <400> 6 Met Met Met Ala Ser Lys Asp Ala Pro Thr Ser Pro Asp Gly Ala Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Gln Ile Ser 20 25 30 Met Asp Pro Val Ala Gly Ala Ser Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Phe Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Ile Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Asp Ala Arg Ile Leu Thr Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Leu Ile Ala Asp Val Arg Thr Leu Glu Pro Val Glu Leu 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Asn Ser Ser Gln Pro 165 170 175 Gln Pro Thr Met Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Thr 180 185 190 Gly Gly Gly Ser Gly Gly Thr Asp Ala Phe Val Val Ala Gly Arg Val 195 200 205 Leu Thr Cys Pro Ala Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro 210 215 220 Ser Val Glu Gln Lys Thr Arg Val Phe Ser Val Pro Asn Ile Pro Leu 225 230 235 240 Lys Asp Leu Ser Asn Ser Arg Val Pro Val Pro Ile Gln Gly Met Phe 245 250 255 Met Ser Pro Asp Val Asn Gln Ser Val Gln Phe Gln Asn Gly Arg Cys 260 265 270 Gln Ile Asp Gly Gln Leu Gln Gly Thr Thr Pro Val Ser Leu Ser Gln 275 280 285 Leu Cys Lys Ile Arg Gly Lys Thr Ser Ser Asn Ala Arg Val Leu Asn 290 295 300 Leu Ser Glu Val Asp Gly Thr Pro Phe Ile Pro Leu Glu Ser Pro Ala 305 310 315 320 Pro Val Gly Phe Pro Asp Leu Gly Gly Cys Asp Trp His Val Asn Phe 325 330 335 Ser Phe Gln Thr Gln Asp Arg Asp Pro Ser Gln Ser Val Thr Phe Ala 340 345 350 Thr Asn Asp Ala Ser Phe Val Pro Tyr Leu Gly Ser Val Ser Pro His 355 360 365 Asn Gly Glu Gly Phe Gln Ala Gly Asp Ile Ile Gly Ser Leu Gly Trp 370 375 380 Ile Ser Ala Pro Ser Asp Asn Ser Gln Phe Asn Val Trp Ala Ile Pro 385 390 395 400 Lys Tyr Gly Ser Ser Leu Gln Met Ser Pro Ile Leu Leu Leu Leu Cys 405 410 415 Ser Pro Arg Leu Trp Glu Val Ile Leu Tyr Phe Tyr Ser Thr Phe Pro 420 425 430 Gly Ser Gly Gln Pro Ser Gln Leu Gln Val Pro Cys Leu Leu Pro Gln 435 440 445 Glu Phe Ile Thr His Phe Cys Asn Glu Gln Ala Pro Ile Ala Gly Glu 450 455 460 Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr Gly Arg Asn Leu Gly 465 470 475 480 Glu Phe Lys Leu Tyr Pro Asp Gly Phe Met Thr Cys Val Pro Asn Ser 485 490 495 Val Ser Ser Gly Pro Gln Thr Leu Pro Ile Asn Gly Val Phe Val Phe 500 505 510 Val Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val Gly Thr Ala 515 520 525 Ser Ala Ala Arg Arg Leu Gly Leu Arg Arg Ile 530 535 <210> 7 <211> 544 <212> PRT <213> Norovirus <400> 7 Met Met Met Ala Ser Lys Asp Ala Pro Thr Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Ile Ser 20 25 30 Met Asp Pro Val Ala Gly Ala Ala Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Ile Asn Met Ile Asp Pro Trp Ile Met Ser Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Val Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro Gln Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ala Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Lys Val Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Ser Cys Ile 115 120 125 Pro Pro Gly Phe Thr Ser Gln Asn Ile Ser Ile Ala Gln Met Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Glu Ile 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Phe His Thr Asn Asp Asn Arg 165 170 175 Pro Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Ala Asn 180 185 190 Gly Ser Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Asp Ser Asn Phe Ser Phe Leu Phe Leu Val Pro Pro Asn 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Ser Val Pro Asn Ile Pro Leu Asn 225 230 235 240 Thr Leu Ser Asn Ser Arg Val Pro Ser Leu Ile Lys Ser Met Thr Ile 245 250 255 Ser Arg Asp Gln Asn Gln Ile Ile Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Pro Thr Ser Val Ser Gln Leu 275 280 285 Cys Lys Ile Arg Gly Thr Thr Tyr His Ala Thr Gly Gly Asn Gly Ile 290 295 300 Asn Leu Thr Glu Leu Asn Gly Glu Pro Tyr His Ala Phe Glu Ser Pro 305 310 315 320 Ala Pro Ile Gly Phe Pro Asp Leu Gly Gly Cys Asp Trp His Leu Thr 325 330 335 Ala Thr Pro Thr Gln Ala Phe Asn Asp Gly Ala Lys Val Val Arg Leu 340 345 350 Ser Val Thr Gln Gly Ala Ala Phe Ala Pro His Leu Gly Thr Ile His 355 360 365 Tyr Thr Thr Thr Asp His Asp Tyr Asp Pro Asn Thr Ser Ile Ile Cys 370 375 380 Thr Leu Asp Trp Leu Ser Gln Thr Thr Gly Gln Asn Asn Val Asp Pro 385 390 395 400 Trp Gln Ile Pro Thr Tyr Gly Ser Thr Leu Thr Glu Ala Ala Gln Leu 405 410 415 Ala Pro Pro Ile Phe Pro Pro Gly Phe Gly Glu Thr Leu Val Phe Phe 420 425 430 Leu Ser Asp Phe Pro Ile Ser Asn Gly Lys Asn Gly Leu Ser Val Pro 435 440 445 Cys Thr Leu Pro Gln Glu Phe Val Thr His Phe Val Asn Glu Gln Ala 450 455 460 Pro Ile Arg Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 His Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Glu Gly Phe Met Thr 485 490 495 Cys Val Pro Asn Thr Ser Gly Gly Gly Pro Gln Thr Leu Pro Ile Asn 500 505 510 Gly Val Phe Val Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Ala Gly Ala Ala Arg Arg Leu Gly Ile Arg Arg Ser 530 535 540 <210> 8 <211> 545 <212> PRT <213> Norovirus <400> 8 Met Met Met Ala Ser Lys Asp Ala Pro Thr Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Ile Ser 20 25 30 Met Glu Pro Val Ala Gly Ala Ala Thr Ala Ala Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Met Asn Asn Tyr Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ala Gln Met Tyr Asn Gly Trp Val Gly Asn Met Lys Val Lys Val Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Ser Cys Ile 115 120 125 Pro Pro Gly Phe Ala Ala Gln Asn Ile Ser Ile Ala Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Glu Ile 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn Thr 165 170 175 Pro Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Ala Ser 180 185 190 Gly Ser Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Ser Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro Asn 210 215 220 Val Glu Gln Lys Thr Lys Pro Phe Ser Val Pro Asn Leu Pro Leu Asn 225 230 235 240 Ile Leu Ser Ser Ser Arg Val Pro Ser Leu Ile Lys Ser Met Met Ile 245 250 255 Ser Arg Asp His Gly Gln Met Val Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Pro Thr Ser Ala Ser Gln Leu 275 280 285 Cys Lys Ile Arg Gly Ser Val Phe His Ala Asn Gly Gly Asn Gly Tyr 290 295 300 Asn Leu Thr Glu Leu Asp Gly Ser Pro Tyr His Ala Phe Glu Ser Pro 305 310 315 320 Ala Pro Ile Gly Phe Pro Asp Leu Gly Glu Cys Asp Trp His Met Glu 325 330 335 Ala Ser Pro Thr Ile Gln Phe Asp Thr Gly Asp Val Ile Lys Gln Ile 340 345 350 Asn Val Lys Gln Glu Ser Ala Phe Ala Pro His Leu Gly Thr Val Gln 355 360 365 Ala Asp Gly Leu Asp Gly Val Ser Ala Asn Thr Asn Met Ile Ala Lys 370 375 380 Leu Gly Trp Val Ser Pro Val Ser Asp Gly His Arg Arg Asp Val Asp 385 390 395 400 Pro Trp Val Ile Pro Arg Tyr Gly Ser Thr Leu Thr Glu Ala Ala Gln 405 410 415 Leu Ala Pro Pro Ile Tyr Pro Pro Gly Phe Gly Glu Ala Ile Val Phe 420 425 430 Phe Met Ser Asp Phe Pro Ile Ala His Gly Thr Asn Gly Leu Ser Val 435 440 445 Pro Cys Thr Ile Pro Gln Glu Phe Val Thr His Phe Val Asn Glu Gln 450 455 460 Ala Pro Thr Arg Gly Glu Ala Ala Leu Leu His Tyr Leu Asp Pro Asp 465 470 475 480 Thr His Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Asp Gly Phe Met 485 490 495 Thr Cys Val Pro Asn Ser Ser Gly Ser Gly Pro Gln Thr Leu Pro Ile 500 505 510 Asn Gly Val Phe Val Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu 515 520 525 Lys Pro Val Gly Thr Ala Gly Pro Ala Arg Arg Leu Gly Ile Arg Arg 530 535 540 Ser 545 <210> 9 <211> 545 <212> PRT <213> Norovirus <400> 9 Met Met Met Ala Ser Lys Asp Ala Pro Ser Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Ile Asn 20 25 30 Met Glu Ser Val Val Gly Ala Ala Thr Ala Thr Ala Thr Ala Gly Gln 35 40 45 Val Asn Leu Ile Asp Pro Trp Ile Met Asn Asn Tyr Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ser Arg Met Tyr Asn Gly Trp Val Gly Asn Met Lys Val Arg Val Met 100 105 110 Leu Ala Gly Asn Ala Phe Ser Ala Gly Lys Ile Ile Ile Cys Cys Ile 115 120 125 Pro Pro Gly Phe Thr Ser Gln Ser Ile Ser Ile Ala Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Asp Val 145 150 155 160 Pro Leu Asp Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn Ala 165 170 175 Gln Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Ala Ser Ser Ser Gly Ser Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Thr Gln Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Asp 210 215 220 Val Glu Gln Lys Thr Lys Pro Phe Ser Val Pro Asn Ile Pro Leu Asn 225 230 235 240 Leu Met Ser Asn Ser Arg Val Pro Ala Leu Ile Asp Gly Met Thr Val 245 250 255 Ser Ser Asp Gln Asn Gln Val Val Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Ala Val Ser Ala Ser Cys Val 275 280 285 Ala Lys Ile Arg Gly Arg Ile Phe Ser Asn Ala Ser His Tyr Gly Ile 290 295 300 Asn Leu Thr Glu Val Asp Gly Thr Gln Tyr His Ala Phe Asp Ser Pro 305 310 315 320 Ala Pro Leu Gly Phe Pro Asp Phe Gly Asn Cys Asp Trp His Val Thr 325 330 335 Gly Thr Lys Ala Ser Gln Gly Asp Leu Gln Thr Asp Asn Pro Thr Ile 340 345 350 Ser Gly Thr Ile Lys Ser Tyr Glu Ser Ser Phe Ala Pro His Leu Gly 355 360 365 Thr Val Arg Ile Glu Gly Asp Asp Asn Glu Leu Ala Arg Phe Asn Gly 370 375 380 Lys Asp Val Leu Leu Asn Leu Thr Trp Phe Ser Gln Arg Asn Gly Ser 385 390 395 400 Gln Leu Asn Leu Trp Thr Ile Pro Ser Tyr Gly Ser Asn Leu Thr Glu 405 410 415 Ala Ser Gln Leu Ala Pro Pro Ile Tyr Pro Pro Gly Phe Gly Glu Ala 420 425 430 Ile Val Tyr Phe Thr Ser Thr Phe Pro Ala Ile Ser Arg Pro Ser Val 435 440 445 Pro Cys Thr Met Pro Gln Glu Phe Val Ser His Phe Val Asn Glu Gln 450 455 460 Ala Pro Thr Arg Gly Glu Ala Ala Leu Leu His Tyr Leu Asp Pro Asp 465 470 475 480 Thr His Arg Asn Leu Gly Glu Phe Lys Met Tyr Pro Glu Gly Phe Phe 485 490 495 Thr Cys Val Pro Asn Ala Gly Gly Ser Gly Pro Gln Thr Leu Pro Ile 500 505 510 Asn Gly Val Phe Val Phe Val Ser Trp Val Ser Arg Tyr Tyr Gln Leu 515 520 525 Lys Pro Val Gly Thr Val Gly Met Thr Arg Arg Leu Gly Leu Met Lys 530 535 540 Gln 545 <210> 10 <211> 530 <212> PRT <213> Norovirus <400> 10 Met Met Met Ala Ser Lys Asp Ala Thr Ser Ser Val Asp Gly Ala Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Ala Ser Asp Pro Leu Ala 20 25 30 Met Asp Pro Val Ala Gly Ser Ser Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Pro Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Ser Leu Gly Pro His Leu Asn Pro Phe Leu Leu His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Ile Met 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Val Ser Cys Ile 115 120 125 Pro Pro Gly Phe Gly Ser His Asn Leu Thr Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Ile Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Arg Asn 165 170 175 Gln Gln Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Thr 180 185 190 Gly Gly Gly Thr Gly Asp Ser Phe Val Val Ala Gly Arg Val Met Thr 195 200 205 Cys Pro Ser Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr Val 210 215 220 Glu Gln Lys Thr Arg Pro Phe Thr Leu Pro Asn Leu Pro Leu Ser Ser 225 230 235 240 Leu Ser Asn Ser Arg Ala Pro Leu Pro Ile Ser Ser Met Gly Ile Ser 245 250 255 Pro Asp Asn Val Gln Ser Val Gln Phe Gln Asn Gly Arg Cys Thr Leu 260 265 270 Asp Gly Arg Leu Val Gly Thr Thr Pro Val Ser Leu Ser His Val Ala 275 280 285 Lys Ile Arg Gly Thr Ser Asn Gly Thr Val Ile Asn Leu Thr Glu Leu 290 295 300 Asp Gly Thr Pro Phe His Pro Phe Glu Gly Pro Ala Pro Ile Gly Phe 305 310 315 320 Pro Asp Leu Gly Gly Cys Asp Trp His Ile Asn Met Thr Gln Phe Gly 325 330 335 His Ser Ser Gln Thr Gln Tyr Asp Val Asp Thr Thr Pro Asp Thr Phe 340 345 350 Val Pro His Leu Gly Ser Ile Gln Ala Asn Gly Ile Gly Ser Gly Asn 355 360 365 Tyr Val Gly Val Leu Ser Trp Ile Ser Pro Pro Ser His Pro Ser Gly 370 375 380 Ser Gln Val Asp Leu Trp Lys Ile Pro Asn Tyr Gly Ser Ser Ile Thr 385 390 395 400 Glu Ala Thr His Leu Ala Pro Ser Val Tyr Pro Pro Gly Phe Gly Glu 405 410 415 Val Leu Val Phe Phe Met Ser Lys Met Pro Gly Pro Gly Ala Tyr Asn 420 425 430 Leu Pro Cys Leu Leu Pro Gln Glu Tyr Ile Ser His Leu Ala Ser Glu 435 440 445 Gln Ala Pro Thr Val Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro 450 455 460 Asp Thr Gly Arg Asn Leu Gly Glu Phe Lys Ala Tyr Pro Asp Gly Phe 465 470 475 480 Leu Thr Cys Val Pro Asn Gly Ala Ser Ser Gly Pro Gln Gln Leu Pro 485 490 495 Ile Asn Gly Val Phe Val Phe Val Ser Trp Val Ser Arg Phe Tyr Gln 500 505 510 Leu Lys Pro Val Gly Thr Ala Ser Ser Ala Arg Gly Arg Leu Gly Leu 515 520 525 Arg Arg 530 <210> 11 <211> 546 <212> PRT <213> Norovirus <400> 11 Met Met Met Ala Ser Lys Asp Ala Pro Gln Ser Ala Asp Gly Ala Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Leu Pro 20 25 30 Met Glu Pro Val Ala Gly Pro Thr Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Val Asn Asn Phe Val Gln Ser Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Ile Leu 100 105 110 Leu Ala Gly Asn Ala Phe Ser Ala Gly Lys Ile Ile Val Cys Cys Val 115 120 125 Pro Pro Gly Phe Thr Ser Ser Ser Leu Thr Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Glu Pro Ile Glu Met 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Thr Asn Asp Asn Gln 165 170 175 Pro Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Gly Ser Gly Ser Ser Asp Ser Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Ala Pro Ser Ser Asp Phe Ser Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Ile Glu Gln Lys Thr Arg Ala Phe Thr Val Pro Asn Ile Pro Leu Gln 225 230 235 240 Thr Leu Ser Asn Ser Arg Phe Pro Ser Leu Ile Gln Gly Met Ile Leu 245 250 255 Ser Pro Asp Ala Ser Gln Val Val Gln Phe Gln Asn Gly Arg Cys Leu 260 265 270 Ile Asp Gly Gln Leu Leu Gly Thr Thr Pro Ala Thr Ser Gly Gln Leu 275 280 285 Phe Arg Val Arg Gly Lys Ile Asn Gln Gly Ala Arg Thr Leu Asn Leu 290 295 300 Thr Glu Val Asp Gly Lys Pro Phe Met Ala Phe Asp Ser Pro Ala Pro 305 310 315 320 Val Gly Phe Pro Asp Phe Gly Lys Cys Asp Trp His Met Arg Ile Ser 325 330 335 Lys Thr Pro Asn Asn Thr Ser Ser Gly Asp Pro Met Arg Ser Val Ser 340 345 350 Val Gln Thr Asn Val Gln Gly Phe Val Pro His Leu Gly Ser Ile Gln 355 360 365 Phe Asp Glu Val Phe Asn His Pro Thr Gly Asp Tyr Ile Gly Thr Ile 370 375 380 Glu Trp Ile Ser Gln Pro Ser Thr Pro Pro Gly Thr Asp Ile Asn Leu 385 390 395 400 Trp Glu Ile Pro Asp Tyr Gly Ser Ser Leu Ser Gln Ala Ala Asn Leu 405 410 415 Ala Pro Pro Val Phe Pro Pro Gly Phe Gly Glu Ala Leu Val Tyr Phe 420 425 430 Val Ser Ala Phe Pro Gly Pro Asn Asn Arg Ser Ala Pro Asn Asp Val 435 440 445 Pro Cys Leu Leu Pro Gln Glu Tyr Ile Thr His Phe Val Ser Glu Gln 450 455 460 Ala Pro Thr Met Gly Asp Ala Ala Leu Leu His Tyr Val Asp Pro Asp 465 470 475 480 Thr Asn Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu 485 490 495 Thr Cys Val Pro Asn Gly Val Gly Ala Gly Pro Gln Gln Leu Pro Leu 500 505 510 Asn Gly Val Phe Leu Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu 515 520 525 Lys Pro Val Gly Thr Ala Ser Thr Ala Arg Gly Arg Leu Gly Val Arg 530 535 540 Arg Ile 545 <210> 12 <211> 544 <212> PRT <213> Norovirus <400> 12 Met Met Met Ala Ser Lys Asp Ala Pro Thr Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Ile Ser 20 25 30 Met Glu Pro Val Ala Gly Ala Ala Thr Ala Ala Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Met Asn Asn Tyr Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ala Gln Met Tyr Asn Gly Trp Val Gly Asn Met Lys Val Lys Val Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Ser Cys Ile 115 120 125 Pro Pro Gly Phe Ala Ser Gln Asn Ile Ser Ile Ala Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn Thr 165 170 175 Pro Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Ala Ser 180 185 190 Gly Ser Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Ser Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro Asn 210 215 220 Val Glu Gln Lys Thr Lys Pro Phe Ser Val Pro Asn Leu Pro Leu Asn 225 230 235 240 Val Leu Ser Asn Ser Arg Val Pro Ser Leu Ile Lys Ser Met Met Val 245 250 255 Ser Gln Asp His Gly Gln Met Val Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Pro Thr Ser Ala Ser Gln Leu 275 280 285 Cys Lys Met Arg Gly Thr Val Tyr His Ala Ser Gly Gly Gln Gly Leu 290 295 300 Asn Leu Thr Glu Ile Asp Gly Thr Pro Tyr His Ala Phe Glu Ser Pro 305 310 315 320 Ala Pro Ile Gly Phe Pro Asp Ile Gly Asp Ser Asp Trp His Ile Asn 325 330 335 Ala Ser Pro Ala Thr Thr Phe Asp Ser Gly Glu Ser Ile Lys Arg Leu 340 345 350 Asp Met Glu Gln Gly Ser Ser Phe Ala Pro His Leu Gly Thr Val His 355 360 365 Tyr Thr Asn Ala Asp Tyr Pro Ala Asn Thr Asp Leu Ile Cys Ser Leu 370 375 380 Glu Trp Leu Ser Pro Pro Ser Gly Gly Thr Pro Asn Lys Val Asn Pro 385 390 395 400 Trp Thr Ile Pro Arg Tyr Gly Ser Thr Leu Thr Glu Ala Ala Gln Leu 405 410 415 Ala Pro Pro Ile Tyr Pro Pro Gly Phe Gly Glu Ala Ile Val Phe Phe 420 425 430 Met Ser Asp Phe Pro Ile Ala Asn Gly Gln Asp Gly Leu Lys Val Pro 435 440 445 Cys Thr Ile Pro Gln Glu Phe Val Thr His Phe Val Asn Glu Gln Ala 450 455 460 Pro Thr Arg Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 His Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Glu Gly Phe Met Thr 485 490 495 Cys Val Pro Asn Ser Ser Gly Ser Gly Pro Gln Thr Leu Pro Ile Asn 500 505 510 Gly Val Phe Thr Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Thr Gly Pro Val Arg Arg Leu Gly Ile Arg Arg Ser 530 535 540 <210> 13 <211> 544 <212> PRT <213> Norovirus <400> 13 Met Met Met Ala Ser Lys Asp Ala Pro Thr Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Ile Ser 20 25 30 Met Glu Pro Val Ala Gly Ala Ala Thr Ala Ala Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Met Asn Asn Tyr Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ala Gln Met Tyr Asn Gly Trp Val Gly Asn Met Lys Val Lys Val Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Ser Cys Ile 115 120 125 Pro Pro Gly Phe Ala Ser Gln Asn Ile Ser Ile Ala Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn Ser 165 170 175 Pro Thr Met Arg Leu Val Cys Met Leu Tyr Thr Pro Leu Arg Ala Ser 180 185 190 Gly Ser Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Ser Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro Asn 210 215 220 Val Glu Gln Lys Thr Lys Pro Phe Ser Val Pro Asn Leu Pro Leu Asn 225 230 235 240 Thr Leu Ser Asn Ser Arg Val Pro Ser Leu Ile Asn Ala Met Met Ile 245 250 255 Ser Arg Asp His Gly Gln Met Val Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Pro Thr Ser Leu Ser Gln Leu 275 280 285 Cys Lys Ile Arg Gly Lys Val Phe Leu Ala Ser Gly Gly Asn Gly Leu 290 295 300 Asn Leu Thr Glu Leu Asp Gly Ser Ala Tyr His Ala Phe Glu Ser Pro 305 310 315 320 Ala Pro Ile Gly Phe Pro Asp Ile Gly Asp Cys Asp Trp His Met Asn 325 330 335 Ala Thr Ala Thr Ser Asn Phe Thr Gly Ser Asn Asp Glu His Gln Ile 340 345 350 Leu Val Lys Gln Glu Ser Thr Phe Ala Pro His Leu Gly His Val Gln 355 360 365 Ala Asp His Leu Pro Glu Val Ala Asn Thr Asp Leu Met Val Ser Leu 370 375 380 Ser Trp Ile Ser Pro Val Ser Asp Gln His Arg Arg Asp Val Asp Pro 385 390 395 400 Trp Val Ile Pro Arg Tyr Gly Ser Thr Leu Thr Glu Ala Ala Gln Leu 405 410 415 Ala Pro Pro Ile Tyr Pro Pro Gly Phe Gly Glu Ala Ile Val Phe Phe 420 425 430 Met Ser Asp Phe Pro Val Val Ser Gly Val Asn Gly Met Arg Ile Pro 435 440 445 Cys Thr Leu Pro Gln Glu Tyr Val Ala His Phe Val Asn Glu Gln Ala 450 455 460 Pro Thr Arg Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 His Arg Asn Leu Gly Glu Phe Lys Ile Tyr Pro Glu Gly Phe Met Thr 485 490 495 Cys Val Pro Asn Ser Ser Gly Thr Gly Pro Gln Thr Leu Pro Ile Asn 500 505 510 Gly Val Phe Thr Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Ala Gly Pro Ala Arg Arg Leu Gly Ile Arg Arg Ser 530 535 540 <210> 14 <211> 533 <212> PRT <213> Norovirus <400> 14 Met Met Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro 20 25 30 Ile Asp Pro Val Ala Gly Ser Ser Thr Ala Leu Ala Thr Ala Gly Gln 35 40 45 Val Asn Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Ala Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys 225 230 235 240 Tyr Leu Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu 245 250 255 Ser Pro Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Ile Asp Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu 275 280 285 Cys Lys Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu 290 295 300 Thr Glu Leu Asp Gly Ser Pro Phe Met Ala Phe Ala Ala Pro Ala Pro 305 310 315 320 Ala Gly Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser 325 330 335 Lys Ile Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Val Asn Ser 340 345 350 Val Lys Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr 355 360 365 Leu Asp Asp Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln 370 375 380 Trp Thr Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp 385 390 395 400 Lys Ile Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala 405 410 415 Pro Ala Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met 420 425 430 Ala Ser Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro 435 440 445 Cys Leu Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala 450 455 460 Pro Ile Gln Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 Asn Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr 485 490 495 Cys Val Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp 500 505 510 Gly Val Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Ala 530 <210> 15 <211> 544 <212> PRT <213> Norovirus <400> 15 Met Met Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Thr 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Pro Ile Pro 20 25 30 Ile Asp Pro Val Ala Gly Ser Ser Thr Ala Leu Ala Thr Ala Gly Gln 35 40 45 Val Asn Leu Ile Asp Pro Trp Ile Ile Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Val Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ser His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Val 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Asp Pro Val Glu Val 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Asn Asn Asp Thr Gln 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Ala Ser Gly Gly Thr Asp Ser Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Gly Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Thr Val Pro Asn Ile Pro Leu Lys 225 230 235 240 Tyr Leu Ser Asn Ser Arg Ile Pro Asn Pro Ile Glu Gly Met Ser Leu 245 250 255 Ser Pro Asp Gln Thr Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Ile Asp Gly Gln Pro Leu Gly Thr Thr Pro Val Ser Val Ser Gln Leu 275 280 285 Cys Lys Phe Arg Gly Arg Ile Thr Ser Gly Gln Arg Val Leu Asn Leu 290 295 300 Thr Glu Leu Asp Gly Ser Pro Phe Met Gly Phe Gly Ala Pro Ala Pro 305 310 315 320 Ala Gly Phe Pro Asp Leu Gly Ser Cys Asp Trp His Ile Glu Met Ser 325 330 335 Lys Ile Pro Asn Ser Ser Thr Gln Asn Asn Pro Ile Val Thr Asn Ser 340 345 350 Val Lys Pro Asn Ser Gln Gln Phe Val Pro His Leu Ser Ser Ile Thr 355 360 365 Leu Asp Glu Asn Val Ser Ser Gly Gly Asp Tyr Ile Gly Thr Ile Gln 370 375 380 Trp Thr Ser Pro Pro Ser Asp Ser Gly Gly Ala Asn Thr Asn Phe Trp 385 390 395 400 Lys Ile Pro Asp Tyr Gly Ser Ser Leu Ala Glu Ala Ser Gln Leu Ala 405 410 415 Pro Ala Val Tyr Pro Pro Gly Phe Asn Glu Val Ile Val Tyr Phe Met 420 425 430 Ala Ser Ile Pro Gly Pro Asn Gln Ser Gly Ser Pro Asn Leu Val Pro 435 440 445 Cys Leu Leu Pro Gln Glu Tyr Ile Thr His Phe Ile Ser Glu Gln Ala 450 455 460 Pro Ile Gln Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 Asn Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Gly Gly Tyr Leu Thr 485 490 495 Cys Val Pro Asn Ser Ser Ser Thr Gly Pro Gln Gln Leu Pro Leu Asp 500 505 510 Gly Val Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys 515 520 525 Pro Val Gly Thr Ala Gly Pro Ala Arg Gly Arg Leu Gly Val Arg Arg 530 535 540 <210> 16 <211> 543 <212> PRT <213> Norovirus <400> 16 Met Met Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Asn 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Asn Ala Glu Pro Leu Pro 20 25 30 Leu Asp Pro Val Ala Gly Ala Ser Thr Ala Leu Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Phe Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Ile 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Ile Ile Ala Asp Val Arg Thr Leu Glu Pro Ile Glu Ile 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Thr Leu Tyr His Thr Asn Asp Asn Gln 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Gly Ser Gly Gly Thr Asp Ala Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Ser Pro Ser Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Ser Val Pro Asn Ile Pro Leu Gln 225 230 235 240 Leu Leu Ser Asn Ser Arg Val Pro Asn Leu Ile Gln Ser Met Val Pro 245 250 255 Ser Pro Asp Gln Ala Gln Asn Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Thr Asp Gly Gln Leu Leu Gly Thr Thr Pro Val Ser Val Ser Gln Ile 275 280 285 Leu Lys Phe Arg Gly Lys Val Ser Ala Gly Ser Lys Val Ile Asn Leu 290 295 300 Thr Glu Leu Asp Gly Ser Pro Phe Leu Ala Phe Glu Ala Pro Ala Pro 305 310 315 320 Thr Gly Phe Pro Asp Leu Gly Thr Ser Asp Trp His Ile Glu Met Ser 325 330 335 Leu Asn Ser Asn Ser Gln Ser Ser Gly Asn Pro Ile Leu Leu Arg Asp 340 345 350 Ile Gln Pro Asn Ser Ser Asp Phe Val Pro His Leu Gly Ser Val Ala 355 360 365 Val Thr Thr Ala Ile Asp Thr Ala Gly Asp Tyr Thr Gly Thr Ile Gln 370 375 380 Trp Thr Ser Gln Pro Ser Asn Val Thr Pro Val Pro Asp Val Asn Phe 385 390 395 400 Trp Thr Ile Pro Gln Tyr Gly Ser Asn Leu Ala Glu Ala Ser Gln Leu 405 410 415 Ala Pro Val Val Tyr Pro Pro Gly Phe Gly Glu Ala Ile Val Tyr Phe 420 425 430 Met Ser Pro Ile Pro Gly Pro Asn Thr Ala His Lys Pro Asn Leu Val 435 440 445 Pro Cys Leu Leu Pro Gln Glu Phe Val Thr His Phe Val Ser Glu Gln 450 455 460 Ala Pro Ser Met Gly Glu Ala Ala Leu Val His Tyr Val Asp Pro Asp 465 470 475 480 Thr Asn Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Glu Gly Phe Ile 485 490 495 Thr Cys Val Pro Asn Gly Thr Gly Pro Gln Gln Leu Pro Leu Asn Gly 500 505 510 Val Phe Val Phe Ala Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro 515 520 525 Val Gly Thr Ala Asn Ser Ala Arg Gly Arg Leu Gly Val Arg Arg 530 535 540 <210> 17 <211> 541 <212> PRT <213> Norovirus <400> 17 Met Met Met Ala Ser Lys Asp Ala Thr Pro Ser Ala Asp Gly Ala Asn 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Asn Ala Glu Pro Leu Pro 20 25 30 Leu Asp Pro Val Ala Gly Ala Ser Thr Ala Leu Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Phe Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Ile 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Val Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Gln Ser Arg Thr Leu Ser Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Thr Leu Glu Pro Leu Glu Ile 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Thr Leu Tyr His Asn Asn Asp Ser Gln 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Thr Gly 180 185 190 Gly Gly Ser Gly Gly Thr Asp Ala Phe Val Val Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Ser Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Thr 210 215 220 Val Glu Gln Lys Thr Arg Pro Phe Ser Val Pro Asn Ile Pro Leu Gln 225 230 235 240 Asn Leu Ser Asn Ser Arg Val Pro Ser Leu Ile Gln Ser Met Val Leu 245 250 255 Ser Ser Asp His Ala Gln Thr Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Thr Asp Gly His Leu Leu Gly Thr Thr Pro Val Ser Ser Gly Gln Leu 275 280 285 Met Lys Phe Arg Gly Lys Val Thr Pro Gly Ser Lys Val Leu Asn Leu 290 295 300 Thr Glu Leu Asp Gly Ser Pro Phe Leu Ala Phe Glu Pro Pro Ala Pro 305 310 315 320 Ala Gly Phe Pro Asp Leu Gly Lys Cys Asp Trp His Ile Glu Met Ser 325 330 335 Leu Tyr Gln Val Asn Asn Gln Asp Asn Pro Ile Val Leu Arg Ala Ile 340 345 350 Glu Pro Asn Ser Ser Ser Phe Val Pro His Leu Gly Ser Val Ser Phe 355 360 365 Asn Gln Asn Val Asp Ala Ala Gly Asp Tyr Val Cys Thr Ile Gln Tyr 370 375 380 Thr Ser Pro Pro Ser Asn Ser His Asp Ala Asp Val Asp Phe Trp Ser 385 390 395 400 Ile Pro Asp Tyr Gly Ser Asn Leu Ala Glu Ala Ser Gln Leu Ala Pro 405 410 415 Val Val Tyr Pro Pro Gly Phe Gly Glu Ala Ile Val Tyr Phe Met Ser 420 425 430 Arg Val Pro Gly Trp Asn Arg Thr Asn Arg Leu Asn Leu Val Pro Cys 435 440 445 Leu Leu Pro Gln Glu Phe Ile Gly His Phe Val Ser Glu Gln Ala Pro 450 455 460 Ala Ile Gly Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr Asn 465 470 475 480 Arg Asn Leu Gly Glu Phe Lys Leu Tyr Pro Glu Gly Phe Ile Thr Cys 485 490 495 Val Pro Asn Gly Thr Gly Pro Gln Gln Leu Pro Leu Asn Gly Val Phe 500 505 510 Val Phe Ser Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val Gly 515 520 525 Thr Ala Ser Ser Ala Arg Gly Arg Leu Gly Ile Arg Arg 530 535 540 <210> 18 <211> 540 <212> PRT <213> Norovirus <400> 18 Met Met Met Ala Ser Lys Asp Val Pro Thr Ser Pro Asp Gly Ala Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Thr Ala Asp Gln Ile Ser 20 25 30 Met Asp Pro Val Ala Gly Ala Ser Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Phe Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Ile Leu 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Asp Ala Arg Ile Leu Thr Ile Ala Gln Ala Thr Leu 130 135 140 Phe Pro His Leu Ile Ala Asp Val Arg Thr Leu Glu Pro Val Glu Leu 145 150 155 160 Pro Leu Glu Asp Val Arg Asn Val Leu Tyr His Asn Ser Ser Gln Pro 165 170 175 Gln Pro Thr Met Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Thr 180 185 190 Gly Gly Gly Ser Gly Gly Thr Asp Ala Phe Val Val Ala Gly Arg Val 195 200 205 Leu Thr Cys Pro Ala Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro 210 215 220 Ser Val Glu Gln Lys Thr Arg Val Phe Ser Val Pro Asn Ile Pro Leu 225 230 235 240 Lys Asp Leu Ser Asn Ser Arg Val Pro Thr Leu Ile Gln Gly Met Phe 245 250 255 Val Ser Pro Asp Val Asn Gln Ser Val Gln Phe Gln Asn Gly Arg Cys 260 265 270 Gln Ile Asp Gly Gln Leu Gln Gly Thr Thr Pro Val Ser Leu Ser Gln 275 280 285 Leu Cys Lys Ile Arg Gly Lys Thr Ser Ser Asn Thr Arg Val Leu Asn 290 295 300 Leu Ser Glu Val Asp Gly Thr Pro Phe Val Pro Leu Glu Ser Pro Ala 305 310 315 320 Pro Val Gly Phe Pro Asp Ile Gly Gly Cys Asp Trp His Val Gly Phe 325 330 335 Thr Phe Glu Ala Arg Asp Gln Gly Pro Ser Gln Asn Val Thr Phe Ala 340 345 350 Thr Asn Asp Ser Ser Phe Val Pro Tyr Leu Gly Ser Ile Ser Pro His 355 360 365 Asn Gly Asp Gly Phe His Ser Gly Asp Ile Ile Gly Ser Leu Asp Trp 370 375 380 Ile Ser Ala Pro Ser Asp Gly Ser Ala Leu Asp Val Trp Ser Ile Pro 385 390 395 400 Lys Tyr Gly Ser Ser Leu Pro Asp Val Thr His Leu Ala Pro Ala Val 405 410 415 Phe Pro Pro Gly Phe Gly Glu Val Ile Leu Tyr Phe His Ser Lys Phe 420 425 430 Pro Gly Ser Gly Pro Thr Asp Lys Leu Arg Val Pro Cys Leu Met Pro 435 440 445 Gln Glu Phe Ile Thr His Phe Cys Asp Glu Gln Ala Pro Ile Ala Gly 450 455 460 Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Ala Gly Arg Asn Leu 465 470 475 480 Gly Glu Phe Lys Leu Tyr Pro Asp Gly Phe Met Thr Cys Val Pro Asn 485 490 495 Ser Ile Ser Ser Gly Pro Gln Thr Leu Pro Ile Asn Gly Val Phe Val 500 505 510 Phe Val Ser Trp Val Ser Arg Phe Tyr Gln Leu Lys Pro Val Gly Thr 515 520 525 Ala Ser Met Ala Arg Arg Leu Gly Leu Arg Arg Ile 530 535 540 <210> 19 <211> 539 <212> PRT <213> Norovirus <400> 19 Met Met Met Ala Ser Lys Asp Ala Pro Ser Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Val Asn Ala Ala Glu Pro Leu Pro 20 25 30 Leu Glu Pro Val Val Gly Ala Ala Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Leu Ile Asp Pro Trp Ile Met Asn Asn Phe Val Gln Ala Pro 50 55 60 Glu Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Gln His Leu 85 90 95 Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Arg Val Arg Val Met 100 105 110 Leu Ala Gly Asn Ala Phe Thr Ala Gly Lys Ile Ile Ile Cys Cys Val 115 120 125 Pro Pro Gly Phe Ala Ser Gln Asn Ile Ser Ile Gly Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Glu Ile 145 150 155 160 Pro Leu Asp Asp Val Arg Asn Val Leu Phe His Thr Asn Glu Ser Arg 165 170 175 Pro Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Ala Gly 180 185 190 Gly Ala Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Ser Pro Asp Phe Asn Phe Leu Phe Leu Val Pro Pro Ser 210 215 220 Val Glu Gln Lys Thr Arg Gln Leu Thr Val Pro Asn Ile Pro Leu Asn 225 230 235 240 Asn Leu Ala Asn Ser Arg Val Pro Ala Met Ile Asn Lys Met Thr Val 245 250 255 Ser Thr Asp Gln Ser Gln Val Val Gln Phe Gln Asn Gly Arg Cys Thr 260 265 270 Leu Glu Gly Gln Leu Leu Gly Thr Thr Pro Val Ser Ala Ser Gln Val 275 280 285 Ala Arg Ile Arg Gly Lys Val Phe Ser Thr Ala Ser Gly Lys Gly Leu 290 295 300 Asn Leu Thr Glu Leu Asp Gly Thr Pro Tyr His Ala Phe Glu Ser Pro 305 310 315 320 Ala Pro Leu Gly Phe Pro Asp Ile Gly Ala Cys Asp Trp His Val Ser 325 330 335 Thr Phe Lys Val Asp Gln Asn Leu Ser Gly Asp Pro Met Ser Arg Leu 340 345 350 Asp Ile Lys Gln Asn Ala Pro Phe Ala Pro His Leu Gly Ser Ile Glu 355 360 365 Phe Thr Ser Asp Gln Glu Pro Thr Gly Asp Gln Leu Gly Thr Leu Ala 370 375 380 Trp Val Ser Pro Ser Thr Ser Gly Ala Arg Val Asp Pro Trp Lys Ile 385 390 395 400 Pro Ser Tyr Gly Ser Thr Val Thr Glu Ser Thr His Leu Ala Pro Pro 405 410 415 Ile Phe Pro Pro Gly Phe Gly Glu Ala Ile Val Tyr Phe Met Ser Asp 420 425 430 Phe Pro Ile Val Ser Gly Asn Thr Ala Gln Val Pro Cys Thr Leu Pro 435 440 445 Gln Glu Phe Val Ser His Phe Val Glu Gln Gln Ala Pro Ile Arg Gly 450 455 460 Glu Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr His Arg Asn Leu 465 470 475 480 Gly Glu Phe Lys Leu Tyr Pro Asp Gly Phe Ile Thr Cys Val Pro Asn 485 490 495 Thr Gly Gly Gly Pro Gln Asn Leu Pro Ile Asn Gly Val Phe Val Phe 500 505 510 Ser Ser Trp Val Ser Arg Tyr Tyr Gln Leu Lys Pro Val Gly Thr Ala 515 520 525 Gly Pro Ala Arg Arg Leu Gly Val Arg Arg Val 530 535 <210> 20 <211> 543 <212> PRT <213> Norovirus <400> 20 Met Met Met Ala Ser Lys Asp Ala Pro Thr Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Ala Asn Thr Ala Glu Pro Leu Pro 20 25 30 Ile Lys Pro Val Ala Gly Ala Ala Thr Ala Val Ala Thr Ala Gly Gln 35 40 45 Val Asn Met Ile Asp Pro Trp Ile Met Asn Asn Phe Val Gln Ala Pro 50 55 60 Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile Leu 65 70 75 80 Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His Leu 85 90 95 Ser Arg Met Tyr Asn Gly Trp Val Gly Asn Met Gln Val Arg Ile Met 100 105 110 Leu Ala Gly Asn Ala Phe Ser Ala Gly Lys Ile Ile Val Cys Cys Ile 115 120 125 Pro Pro Gly Phe Ser Ser Gln Ser Ile Ser Ile Ala Gln Ala Thr Met 130 135 140 Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Asp Val 145 150 155 160 Pro Leu Asp Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn Pro 165 170 175 Gln Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg Ser Gly 180 185 190 Gly Thr Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg Val Leu 195 200 205 Thr Cys Pro Thr Pro Asp Phe Ser Phe Leu Phe Leu Val Pro Pro Asp 210 215 220 Ile Glu Gln Arg Thr Lys Pro Phe Ser Val Pro Asn Ile Pro Met Asn 225 230 235 240 Leu Met Ser Asn Ser Arg Val Ser Met Leu Ile Asp Gly Met Met Val 245 250 255 Ser Asn Asp Gln Asn Gln Val Pro Gln Phe Gln Asn Gly Arg Val Thr 260 265 270 Leu Asp Gly Gln Leu Gln Gly Thr Thr Thr Val Ser Ala Ala Cys Val 275 280 285 Ala Arg Met Arg Gly Arg Ile Phe Asn Asn Asn Gly Asn Tyr Gly Val 290 295 300 Asn Leu Thr Glu Leu Asp Gly Asn Pro Tyr His Ala Phe Asp Ser Pro 305 310 315 320 Ala Pro Leu Gly Phe Pro Asp Phe Gly Asn Cys Asp Leu His Met Thr 325 330 335 Phe Val Lys Ile Asn Pro Asn Glu Leu Ser Ser Gly Asp Pro Ser Gly 340 345 350 Lys Val Val Ile Arg Ser Tyr Asp Ala Thr Phe Ala Pro His Leu Gly 355 360 365 Thr Val Lys Leu Glu Asn Asp Asp Glu Leu Ala Arg Phe Val Gly Lys 370 375 380 Glu Val Val Leu Glu Leu Thr Trp Val Ser Asn Arg Glu Gly Ala Thr 385 390 395 400 Leu Asn Leu Trp Ala Val Pro Asn Tyr Gly Ser Ser Leu Thr Gln Ala 405 410 415 Ser Gln Leu Ala Pro Pro Ile Tyr Pro Pro Gly Phe Gly Glu Ala Ile 420 425 430 Val Tyr Phe Thr Ser Thr Phe Pro Thr Val Ser Asn Pro Lys Val Pro 435 440 445 Cys Thr Leu Pro Gln Glu Phe Val Ser His Phe Val Asn Glu Gln Ala 450 455 460 Pro Thr Arg Gly Asp Ala Ala Leu Leu His Tyr Val Asp Pro Asp Thr 465 470 475 480 His Arg Asn Leu Gly Glu Phe Lys Met Tyr Pro Glu Gly Tyr Met Thr 485 490 495 Cys Val Pro Asn Ala Gly Gly Gly Pro Gln Thr Leu Pro Ile Asn Gly 500 505 510 Val Phe Val Phe Ile Ser Trp Val Ser Arg Tyr Tyr Gln Leu Lys Pro 515 520 525 Val Gly Thr Ala Gly Ala Ala Arg Arg Leu Gly Leu Arg Arg Ser 530 535 540 <210> 21 <211> 550 <212> PRT <213> Norovirus <400> 21 Met Met Met Ala Ser Lys Asp Ala Thr Ser Asn Met Asp Gly Thr Ser 1 5 10 15 Gly Ala Gly Gln Leu Val Pro Glu Asn Asn Asn Thr Ser Glu Pro Ile 20 25 30 Asn Met Glu Pro Val Ala Gly Ala Val Thr Ala Ala Ala Thr Ala Gly 35 40 45 Gln Val Asn Met Ile Asp Pro Trp Ile Met Asn Asn Tyr Val Gln Ala 50 55 60 Pro Gln Gly Glu Phe Thr Ile Ser Pro Asn Asn Thr Pro Gly Asp Ile 65 70 75 80 Leu Phe Asp Leu Gln Leu Gly Pro His Leu Asn Pro Phe Leu Ala His 85 90 95 Leu Ser Gln Met Tyr Asn Gly Trp Val Gly Asn Met Lys Val Arg Val 100 105 110 Val Leu Ala Gly Asn Ala Phe Ser Ala Gly Lys Ile Ile Val Cys Cys 115 120 125 Ile Pro Pro Gly Phe Ser Ala Pro Asn Ile Ser Ile Ala Gln Ala Thr 130 135 140 Met Phe Pro His Val Ile Ala Asp Val Arg Val Leu Glu Pro Ile Asp 145 150 155 160 Ile Pro Leu Asp Asp Val Arg Asn Val Leu Phe His Asn Asn Asp Asn 165 170 175 Gly Asn Gln Thr Met Arg Leu Leu Cys Met Leu Tyr Thr Pro Leu Arg 180 185 190 Ser Gly Gly Thr Ser Ser Gly Thr Asp Pro Phe Val Ile Ala Gly Arg 195 200 205 Val Leu Thr Cys Pro Thr Pro Asp Phe Asn Phe Leu Phe Leu Val Pro 210 215 220 Pro Thr Val Glu Gln Lys Thr Lys Gln Phe Ser Val Pro Asn Leu Pro 225 230 235 240 Leu Asn Val Met Ser Asn Ser Arg Val Pro Ser Leu Leu Asn Ala Met 245 250 255 Val Val Ser Pro Asp Gln Ala Gln Val Val Gln Phe Gln Asn Gly Arg 260 265 270 Cys Thr Leu Asp Gly Gln Met Leu Gly Thr Thr Thr Val Ser Ala Ser 275 280 285 Cys Val Ala Arg Phe Arg Gly Lys Thr Phe Gln Ala Pro Asp Asn Arg 290 295 300 Leu Gly Ile Asn Leu Ala Glu Ile Ser Gly Glu Pro Tyr His Ala Phe 305 310 315 320 Glu Ser Pro Ala Pro Leu Gly Phe Pro Asp Phe Gly Asp Gly Asp Trp 325 330 335 His Val Thr Ala Thr Lys Val Thr Pro Ser Gln Leu Glu Ala Asn Asp 340 345 350 Pro Val Val Met Gly Asn Val Gln Pro Tyr Asn Pro Gln Phe Ala Pro 355 360 365 His Leu Gly Thr Leu Val Val Glu Asn Pro Thr Pro Asp Asn Val Thr 370 375 380 Thr Gly Thr Asp Leu Leu Phe Asn Ile Thr Trp Leu Ser Asn Arg Ala 385 390 395 400 Asn Asn Arg Phe Asn Pro Trp Val Ile Pro Asn Tyr Gly Ser Thr Leu 405 410 415 Thr Glu Ala Ala Gln Leu Ala Pro Ser Ile Phe Pro Pro Gly Phe Gly 420 425 430 Glu Thr Ile Val Tyr Phe Asn Ser Thr Phe Pro Ala Val Gly Ala Thr 435 440 445 Thr His Ala Ala Ile Pro Cys Leu Leu Pro Gln Glu Phe Val Ala His 450 455 460 Phe Val Asn Glu Gln Ala Pro Ile Arg Gly Glu Ala Ala Leu Leu His 465 470 475 480 Tyr Ile Asp Pro Asp Thr His Arg Asn Leu Gly Glu Phe Lys Ile Tyr 485 490 495 Pro Glu Gly Phe Val Thr Cys Val Pro Asn Val Gly Gly Thr Gly Pro 500 505 510 Gln Ser Leu Pro Thr Asn Gly Ile Phe Val Phe Val Ser Trp Val Ser 515 520 525 Arg Tyr Tyr Gln Leu Lys Pro Val Gly Thr Ala Gly Gln Ala Arg Arg 530 535 540 Leu Gly Phe Arg Arg Val 545 550 <210> 22 <211> 538 <212> PRT <213> Norovirus <400> 22 Met Lys Met Ala Ser Asn Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Met Pro 65 70 75 80 Leu Ser Pro Glu Leu Asn Pro Tyr Leu Ser His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Ile Pro Pro Asn Phe 115 120 125 Pro Thr Asp Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ala Asn Asp Ser Thr Leu 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Val Asp Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Thr Pro Leu Glu Lys Leu His Thr Gly Pro Asn Asn Ser 245 250 255 Ile Val Val Gln Pro Gln Asn Gly Arg Cys Thr Ile Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Thr Val Asn Ile Cys Asn Phe Arg Gly 275 280 285 Ser Thr Thr Arg Ala Gly Gln Ser His Ala Tyr Thr Met Asn Leu Val 290 295 300 Ser Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Val Gly Met Leu Ser Gln 325 330 335 Thr Thr Arg Glu Asn Ser Ser Thr Arg Ala His Lys Ala Thr Val Ser 340 345 350 Thr Gly Asp Ala His Phe Thr Pro Lys Ser Gly Ser Val Leu Phe Thr 355 360 365 Thr Asp Thr Asp Asp Leu Gln Asn Gly Gln Asn Thr Arg Phe Thr Pro 370 375 380 Val Gly Val Ala Gln Asp Gly Glu Pro His Gln Asn Glu Pro Gln Gln 385 390 395 400 Trp Arg Leu Pro Asn Tyr Ser Gly Thr Pro Gly His Asn Val His Leu 405 410 415 Ala Pro Pro Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe Phe 420 425 430 Arg Ser Thr Met Pro Gly Cys Gly Gly Tyr Pro Asn Met Asp Leu Asp 435 440 445 Cys Leu Leu Pro Gln Glu Trp Val Arg His Phe Tyr Gln Glu Ala Ala 450 455 460 Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp Thr 465 470 475 480 Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ala Gly Tyr Ile Thr 485 490 495 Val Ser His Thr Gly Pro Tyr Asp Leu Val Ile Pro Pro Asn Gly Tyr 500 505 510 Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ala Leu Ala Pro Met 515 520 525 Gly Thr Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 23 <211> 543 <212> PRT <213> Norovirus <400> 23 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Thr Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Gly Ala Ile Ala Ala Pro Leu Thr Gly Gln Thr Asn Phe Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Tyr Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Phe Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Ile Asp Val Gln Val Ile Met Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Ile Asp Asn Ile Ser Pro Pro Gln Ile Thr Met Phe Pro His Ile 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Asn Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Ser Phe Phe His Tyr Ser Gln Asn Asn Glu Pro Arg Met 165 170 175 Arg Leu Leu Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Ala 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Lys Pro Ser Ala 195 200 205 Asp Phe Glu Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Ile Pro Ile Leu Thr Ile Gly Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Val Ala Ile Asp Met Leu His Thr Ser Pro Thr Asp Asn 245 250 255 Phe Ile Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Val Thr Ser Asn Ile Cys Ala Phe Arg Gly 275 280 285 Ser Ile Ser Gly His Glu Asn Asn Gly Asp Gln His Gln Trp His Phe 290 295 300 Ser Ile Thr Asn Pro Asn Gly Thr Pro Phe Asp Pro Thr Glu Asp Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Lys Gly Gln Leu Tyr Gly Val 325 330 335 Ile Ser Gln Arg Asn Arg Glu Gly Ser Pro Gly Asn Gly Asn Gln Lys 340 345 350 Ala Asn Arg Ser His Glu Gly Val Ile Ser Thr Val Ala Pro Arg Phe 355 360 365 Thr Pro Lys Leu Gly Ser Val Met Ile Gly Thr Trp Thr Thr Asp Asp 370 375 380 Ile Gln Asp Gln Pro Ser Arg Phe Thr Pro Val Gly Leu Asn Asp Asp 385 390 395 400 Asp Asn Tyr Lys Gln Trp Glu Leu Pro Asn Tyr Ser Gly Ala Leu Thr 405 410 415 Leu Asn Met Gly Leu Ala Pro Ser Val Phe Pro Thr Tyr Pro Gly Glu 420 425 430 Gln Leu Leu Phe Phe Arg Ser Tyr Ile Pro Met Lys Gly Gly Tyr Gly 435 440 445 Ser Pro Tyr Ile Asp Cys Leu Ile Pro Gln Glu Trp Ile Ser His Phe 450 455 460 Tyr Gln Glu Ser Ala Pro Ser Gln Thr Asp Val Ala Leu Ile Arg Tyr 465 470 475 480 Val Asn Pro Asp Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Arg 485 490 495 Gln Gly Tyr Ile Thr Val Ala Lys Thr Gly Asp Ser Pro Ile Asn Val 500 505 510 Pro Ala Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Ser Gln Phe Tyr 515 520 525 Ser Leu Ala Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Ile Gln 530 535 540 <210> 24 <211> 555 <212> PRT <213> Norovirus <400> 24 Met Arg Met Ala Ser Ser Asp Ala Pro Val Ser Gly Thr Asp Gly Ala 1 5 10 15 Ala Gly Leu Val Pro Glu Ser Gln Gln Glu Val Leu Pro Leu Glu Pro 20 25 30 Val Ala Gly Val Gln Leu Ala Ala Pro Val Ala Gly Gln Ser Asn Ile 35 40 45 Ile Asp Pro Trp Ile Arg Met Asn Phe Val Gln Ala Pro Ala Gly Glu 50 55 60 Phe Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Val Leu Ile Asp Leu 65 70 75 80 Glu Leu Gly Pro Glu Leu Asn Pro Tyr Leu Asn His Leu Ala Arg Met 85 90 95 Tyr Asn Gly Tyr Val Gly Gly Met Glu Val Glu Val Val Leu Ala Gly 100 105 110 Asn Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Val Pro Pro Ser 115 120 125 Phe Pro Thr His Gly Ile Ser Ala Ala Gln Ala Thr Met Leu Pro His 130 135 140 Val Ile Val Asp Val Arg Gln Leu Glu Pro Val Arg Leu Pro Leu Pro 145 150 155 160 Asp Val Arg Asn Val Met Phe His Phe Cys Gln Glu Asn Lys Glu Pro 165 170 175 Arg Met Arg Ile Val Ala Ile Leu Tyr Thr Pro Leu Arg Ala Asn Gly 180 185 190 Ala Gly Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro 195 200 205 Ser Pro Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Ser Val Glu Ser 210 215 220 Lys Leu Lys Gln Phe Thr Leu Pro Asn Leu Gln Pro Asn Glu Met Thr 225 230 235 240 Asn Ser Arg Phe Pro Thr Gly Ile Thr Gln Leu Tyr Thr Ser Pro Asn 245 250 255 Thr Asn Leu Val Val Gln Phe Gln Asn Gly Arg Cys Leu Leu Asp Gly 260 265 270 Thr Leu Leu Gly Thr Thr Pro Val Arg Ala Ala Asp Ile Cys Ser Phe 275 280 285 Arg Gly Val Thr Ser Thr Glu Val Asp Ala Thr Asp Ser Pro Arg Val 290 295 300 Ala Gly Ser His Arg Ile Met Val Gln Leu Lys Glu Pro Asp Gly Glu 305 310 315 320 Glu Phe Ser Pro Thr Gly Pro Asn Pro Ala Pro Val Gly Thr Pro Asp 325 330 335 Phe Gln Ala Ala Ile Phe Gly Thr Leu Ser Gln Arg Asn Thr Gly Gly 340 345 350 Thr Gly Gln Asn Ser Asn Arg Ala His Phe Ala Tyr Phe Tyr Thr Arg 355 360 365 Asn Pro Thr Phe Ala Pro Gly Ile Gly Thr Val Val Phe Ser Phe Asp 370 375 380 Thr Thr Asp Phe Gln Asn Arg Gln Pro Thr Lys Phe Ser Pro Ser Gly 385 390 395 400 Val Phe Asp Asp Asp Ser Ser Glu Pro Phe Asn Gln Phe Ser Leu Pro 405 410 415 Tyr Tyr Asn Gly Ser Leu Gly Ala Val Asp Ala Gly Lys Leu Ala Pro 420 425 430 Pro Val Ala Pro Asn Tyr Pro Gly Glu Gln Ile Leu Tyr Phe Arg Gly 435 440 445 Asn Ile Pro Phe Lys Gly Gly Tyr Gly Glu Gly Glu Ile Asp Ser Leu 450 455 460 Leu Pro Gln Glu Trp Ile Thr His Phe Tyr Ala Glu Gln Ala Pro Thr 465 470 475 480 Gln Gly Asp Ala Ala Leu Leu Arg Tyr Tyr Asn Pro Asp Thr Gly Arg 485 490 495 Val Leu Phe Glu Cys Lys Leu His Arg Glu Gly Phe Ile Thr Ile Asn 500 505 510 Tyr Thr Gly Ser Asn Ala Leu Ala Val Pro Val Asn Gly Val Phe Arg 515 520 525 Phe Glu Gly Trp Val Asn Lys Phe Tyr Thr Leu Thr Pro Met Gly Asn 530 535 540 Gly Asn Gly Arg Arg Gly Arg Arg Arg Glu Leu 545 550 555 <210> 25 <211> 535 <212> PRT <213> Norovirus <400> 25 Met Lys Met Ala Ser Asn Asp Ala Asn Pro Ser Ser Asp Gly Ser Ala 1 5 10 15 Asn Leu Val Pro Glu Ile Ser Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Val Leu Leu Asn Leu Pro 65 70 75 80 Leu Ser Pro Asp Ile Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Glu Val Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Pro Glu Asn Leu Ser Pro Ser Gln Ile Thr Met Leu Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Arg Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Ser Arg Glu Asn Asp Ser Thr Leu 165 170 175 Arg Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Lys Ser 210 215 220 Lys Pro Phe Thr Ile Pro Met Leu Thr Ile Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ala Pro Leu Glu Leu Met Thr Thr Gly Pro Ser His Asp 245 250 255 Ile Val Val Gln Pro Gln Asn Gly Arg Cys Thr Ile Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Ser Leu Arg Gly 275 280 285 Val Pro Thr Lys Arg Thr Asn Gly Asn Asp Asn Cys Phe Val Gln Leu 290 295 300 Glu Asn Pro Asn Gly Ser Ala Tyr Asp Pro Thr Glu Asp Ile Pro Ala 305 310 315 320 Val Leu Gly Ser Pro Asp Phe Val Gly Glu Leu Tyr Gly Thr Ile Thr 325 330 335 Gln Arg Ser Ser Asp Asn Ser Thr Arg Ala His Pro Phe Thr Leu Asn 340 345 350 Thr Gly Ser Pro Arg Tyr Thr Pro Lys Ile Gly Ser Val Asp Ile Arg 355 360 365 Val Thr Asp Val Ser Asp Leu Gln Asp His Asp Pro Val Lys Leu Thr 370 375 380 Pro Val Gly Leu Ser Gly Asp Arg Gly Ser Ile His Gln Trp Gln Leu 385 390 395 400 Pro Asn Tyr Ser Gly Val Ala Thr His Asn Met His Leu Ala Pro Ser 405 410 415 Val Ala Pro Leu Phe Pro Gly Glu Gln Ile Leu Phe Phe Arg Ser Thr 420 425 430 Val Pro Gly Cys Gly Gly Tyr Pro Asn Ser Asn Ile Asp Cys Leu Ile 435 440 445 Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Gly Ala Pro Ala Arg 450 455 460 Thr Asp Val Ala Leu Leu Arg Phe Ile Asn Pro Asp Thr Gly Arg Val 465 470 475 480 Leu Phe Glu Cys Lys Leu His Lys His Gly Phe Ile Thr Val Ala Tyr 485 490 495 Ser Gly Asn His Asp Leu Val Met Pro Pro Asn Gly Tyr Phe Arg Phe 500 505 510 Glu Ser Trp Val Asn Gln Phe His Thr Leu Ala Pro Met Gly Thr Gly 515 520 525 Ser Gly Arg Arg Arg Ile Gln 530 535 <210> 26 <211> 555 <212> PRT <213> Norovirus <400> 26 Met Lys Met Ala Ser Lys Asp Ala Ser Pro Ser Thr Asp Gly Thr Ala 1 5 10 15 Asn Leu Val Pro Glu Ser Gln Gln Glu Val Leu Ala Leu Gln Pro Val 20 25 30 Ala Gly Ala Gln Ile Ala Ala Pro Val Ala Gly Gln Phe Asn Val Ile 35 40 45 Asp Pro Trp Ile Tyr Gln Asn Phe Val Gln Ala Pro Glu Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Thr Gly Glu Ile Leu Met Asn Leu Glu 65 70 75 80 Leu Gly Pro Gln Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Ala Tyr Ala Gly Gly Phe Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Val Cys Ala Val Pro Pro Asn Phe 115 120 125 Pro Leu Gln Asn Ile Ser Ala Ala Gln Ala Thr Gln Leu Pro His Val 130 135 140 Val Val Asp Val Arg Gln Leu Glu Pro Val Val Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Ala Gly Phe Tyr His Tyr Asn Gln Val Glu Glu Ser Arg Met 165 170 175 Arg Leu Val Ala Ile Leu Tyr Thr Pro Leu Arg Thr Asn Ser Ala Gly 180 185 190 Asp Asp Ala Phe Thr Val Ser Cys Arg Ile Leu Thr Arg Pro Ala Pro 195 200 205 Asp Phe Ser Phe Phe Phe Leu Ile Pro Pro Thr Ile Glu Ser Lys Thr 210 215 220 Thr Pro Phe Thr Leu Pro Arg Leu Pro Ile Ser Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Leu Val Ile Lys Gly Met Val Val Asp Pro Asn Leu Pro 245 250 255 Leu Gln Ala Asn Phe Gln Asn Gly Arg Ile Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Leu Pro Thr Ser Thr Ser Ile Gly Arg Ile Ser Gly 275 280 285 Thr His Met Ser Ser Thr Pro Ser Arg Ile Ile Gln His Glu Asp Ser 290 295 300 Gly Asp Ser Thr Gln Pro Arg Val Phe Asn Pro Val Trp Met Asp Leu 305 310 315 320 Thr Glu Asn Asn Trp Thr Glu Phe Gln Pro Phe Asn Asp Gln Pro Ala 325 330 335 Pro Leu Gly Cys Pro Asp Phe Lys Ala Lys Ile Leu Gly Thr Leu Ile 340 345 350 Arg Gln Pro Asn Asn Gly Ser Tyr Tyr Phe Asp Ala Tyr Leu Asp Thr 355 360 365 Arg Gln His Gly Thr Phe Ala Pro Tyr Thr Gly His Ala Ala Val His 370 375 380 Ser Asp Gln Gln Ala Gly His Leu Ala Gln Gly Tyr Lys Ile Gln Phe 385 390 395 400 Ser Pro Thr Gly Ile Glu Ser Asp Gln Asn Thr Asp Leu Asn Gln Leu 405 410 415 Pro Asp Tyr Gly Gly Ala Met Thr Val Ser Lys Gly Leu Ala Pro Ala 420 425 430 Ala Ala Pro Asp Phe Pro Gly Glu Met Ile Leu Tyr Phe Val Ser Asp 435 440 445 Met Pro Val Arg Asn Pro Asn Gly Glu Arg Arg Asp Thr Glu Ile Leu 450 455 460 Cys Leu Leu Pro Gln Glu Met Val Thr His Phe Tyr Glu Gln Gln Ala 465 470 475 480 Pro Ser Gln Gly Asp Val Ala Leu Val Arg Tyr Ile Asn Ala Glu Thr 485 490 495 Gly Arg Val Met Phe Glu Gly Lys Leu His Arg Asn Gly Phe Phe Thr 500 505 510 Val Ser Ala Thr Ala Arg Thr Leu Ile Val Pro Asp Gly Tyr Phe Arg 515 520 525 Phe Asp Ser Trp Val Asn Arg Phe Tyr Thr Leu Ser Pro Met Gly Thr 530 535 540 Gly Asn Gly Arg Arg Arg Ala Arg Met Leu Glu 545 550 555 <210> 27 <211> 535 <212> PRT <213> Norovirus <400> 27 Met Lys Met Ala Ser Asn Asp Val Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Val Ser Asn Glu Thr Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Ile Ala Ala Pro Leu Thr Gly Gln Asn Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Met Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Val Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Phe Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Leu Val Phe Ala Ala Ile Pro Pro His Phe 115 120 125 Pro Leu Glu Asn Leu Ser Pro Gly Gln Ile Thr Met Phe Pro His Val 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Leu Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Phe His Tyr Asn Gln Gln Pro Glu Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Gly Glu Leu Ser Asn Ser 225 230 235 240 Arg Phe Pro Val Pro Ile Asp Glu Leu Tyr Thr Ser Pro Asn Glu Gly 245 250 255 Val Val Val Gln Pro Gln Asn Gly Arg Ser Thr Leu Asp Gly Glu Leu 260 265 270 Leu Gly Thr Thr Gln Leu Val Pro Ser Asn Ile Cys Ala Leu Arg Gly 275 280 285 Arg Ile Asn Ala Gln Val Pro Asp Asp His His Gln Trp Asn Leu Gln 290 295 300 Val Thr Asn Ala Asn Gly Thr Ser Phe Asp Pro Thr Glu Asp Val Pro 305 310 315 320 Ala Pro Leu Gly Thr Pro Asp Phe Leu Ala Asn Ile Tyr Gly Val Thr 325 330 335 Ser Gln Arg Asn Pro Asp Asn Thr Cys Arg Ala His Asp Gly Val Leu 340 345 350 Ala Thr Trp Ser Pro Lys Phe Thr Pro Lys Leu Gly Ser Val Val Leu 355 360 365 Gly Thr Trp Glu Glu Ser Asp Leu Asp Leu Asn Gln Pro Thr Arg Phe 370 375 380 Thr Pro Val Gly Leu Tyr Asp Thr Asn His Phe Asp Gln Trp Ile Leu 385 390 395 400 Pro Asn Tyr Ser Gly Arg Leu Thr Leu Asn Met Asn Leu Ala Pro Ser 405 410 415 Val Ala Pro Leu Phe Pro Gly Glu Gln Ile Leu Phe Phe Arg Ser His 420 425 430 Ile Pro Leu Lys Gly Gly Thr Ser Asn Gly Ala Ile Asp Cys Leu Leu 435 440 445 Pro Gln Glu Trp Ile Gln His Phe Tyr Gln Glu Ser Ala Pro Ser Pro 450 455 460 Thr Asp Val Ala Leu Ile Arg Tyr Thr Asn Pro Asp Thr Gly Arg Val 465 470 475 480 Leu Phe Glu Ala Lys Leu His Arg Gln Gly Phe Ile Thr Val Ala Asn 485 490 495 Ser Gly Ser Arg Pro Ile Val Val Pro Pro Asn Gly Tyr Phe Arg Phe 500 505 510 Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu Ala Pro Met Gly Thr Gly 515 520 525 Asn Gly Arg Arg Arg Val Gln 530 535 <210> 28 <211> 542 <212> PRT <213> Norovirus <400> 28 Met Lys Met Ala Ser Ile Asp Ala Ala Pro Ser Thr Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ser Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Leu Ala Ala Pro Val Thr Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Ala Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Val Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Met Glu Val Gln Val Met Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Leu Val Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Val Glu Asn Leu Ser Pro Gln Gln Ile Thr Met Phe Pro His Val 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Leu Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Phe His Tyr Asn Gln Lys Asp Asp Pro Lys Met 165 170 175 Arg Ile Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Thr Tyr Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Leu Gly Glu Leu Ser Asn Ser 225 230 235 240 Arg Phe Pro Val Ser Ile Asp Gln Met Tyr Thr Ser Pro Asn Glu Val 245 250 255 Ile Ser Val Gln Cys Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Gln Val Ser Gly Ile Cys Ala Phe Lys Gly 275 280 285 Glu Val Thr Ala His Leu His Asp Asn Asp His Leu Tyr Asn Val Thr 290 295 300 Ile Thr Asn Leu Asn Gly Ser Pro Phe Asp Pro Ser Glu Asp Ile Pro 305 310 315 320 Ala Pro Leu Gly Val Pro Asp Phe Gln Gly Arg Val Phe Gly Val Ile 325 330 335 Ser Gln Arg Asp Lys His Asn Ser Pro Gly His Asn Glu Pro Ala Asn 340 345 350 Arg Gly His Asp Ala Val Val Pro Thr Tyr Thr Ser Gln Tyr Thr Pro 355 360 365 Lys Leu Gly Gln Ile Gln Ile Gly Thr Trp Gln Thr Asp Asp Leu Thr 370 375 380 Val Asn Gln Pro Val Lys Phe Thr Pro Val Gly Leu Asn Asp Thr Glu 385 390 395 400 His Phe Asn Gln Trp Val Val Pro Arg Tyr Ala Gly Ala Leu Asn Leu 405 410 415 Asn Thr Asn Leu Ala Pro Ser Val Ala Pro Val Phe Pro Gly Glu Arg 420 425 430 Leu Leu Phe Phe Arg Ser Tyr Ile Pro Leu Lys Gly Gly Tyr Gly Asn 435 440 445 Pro Ala Ile Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr 450 455 460 Gln Glu Ala Ala Pro Ser Met Ser Glu Val Ala Leu Val Arg Tyr Ile 465 470 475 480 Asn Pro Asp Thr Gly Arg Ala Leu Phe Glu Ala Lys Leu His Arg Ala 485 490 495 Gly Phe Met Thr Val Ser Ser Asn Thr Ser Ala Pro Val Val Val Pro 500 505 510 Ala Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser 515 520 525 Leu Ala Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Val Gln 530 535 540 <210> 29 <211> 542 <212> PRT <213> Norovirus <400> 29 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Thr Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Gly Ala Ile Ala Ala Pro Leu Thr Gly Gln Thr Asn Phe Ile 35 40 45 Asp Pro Trp Ile Arg Gly Asn Tyr Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Phe Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Ile Asp Val Gln Val Ile Met Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Val Glu Asn Ile Ser Pro Pro Gln Ile Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Asn Ile Pro Val Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Phe His Tyr Asn Gln Asp Arg Asp Ser Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Thr 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Lys Pro Ser Ala 195 200 205 Asp Phe Glu Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Ile Pro Ile Leu Thr Ile Gly Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Leu Pro Ile Asp Met Leu Tyr Thr Ser Pro Thr Glu Asn 245 250 255 Leu Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Glu Gly Glu Leu 260 265 270 Leu Gly Thr Thr Gln Leu Val Thr Pro Ser Ile Cys Ser Leu Arg Gly 275 280 285 Ala Ile Thr Gly His Glu Gly Asn Asp Asp Asp His Lys Trp His Met 290 295 300 Thr Val Thr Ser Pro Asn Gly Ala Ala Phe Asp Pro Thr Glu Asp Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Thr Gly Asp Ile Tyr Gly Val 325 330 335 Leu Ser Gln Arg Asp Arg Asn Ile Asn Pro Gly Gln Thr Ala Pro Ala 340 345 350 Asn Arg Ala His Glu Ala Val Val Ser Thr Arg Ser Asn Lys Phe Thr 355 360 365 Pro Lys Leu Gly Ser Val Met Ile Ala Thr Trp Glu Thr Thr Asp Val 370 375 380 Leu Gln Gln Pro Thr Lys Phe Thr Pro Val Gly Leu Glu Ser Pro Asn 385 390 395 400 His Tyr Asn Gln Trp Gln Leu Pro Asn Tyr Ser Gly Ala Leu Thr Leu 405 410 415 Asn Met Gly Leu Ala Pro Ser Val Phe Pro Thr Tyr Pro Gly Glu Gln 420 425 430 Ile Leu Phe Phe Arg Ser Phe Ile Pro Leu Lys Gly Gly Tyr Gly Asn 435 440 445 Ser Ala Ile Asp Cys Leu Val Pro Gln Glu Trp Ile Gln His Phe Tyr 450 455 460 Gln Glu Ser Ala Pro Ser Gln Thr Asp Val Ala Leu Ile Arg Tyr Val 465 470 475 480 Asn Pro Glu Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Arg Gln 485 490 495 Gly Phe Ile Thr Val Ala Lys Thr Gly Asp Ser Pro Ile Asn Val Pro 500 505 510 Ala Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Pro Phe Tyr Ser 515 520 525 Leu Ala Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Asn Gln 530 535 540 <210> 30 <211> 548 <212> PRT <213> Norovirus <400> 30 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Ala Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Ile Ala Ala Pro Leu Thr Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Met Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Val Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Ile Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Ile Pro Pro Asn Phe 115 120 125 Pro Ile Asp Asn Leu Ser Ala Ala Gln Ile Thr Met Cys Pro His Val 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Asn Leu Pro Met Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Phe His Tyr Asn Gln Gly Ser Asp Ser Arg Leu 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Ser Phe Asn Phe Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Ser Glu Met Ser Asn Ser 225 230 235 240 Arg Phe Pro Val Pro Ile Asp Ser Leu His Thr Ser Pro Thr Glu Asn 245 250 255 Ile Val Val Gln Cys Gln Asn Gly Arg Val Thr Leu Asp Gly Glu Leu 260 265 270 Met Gly Thr Thr Gln Leu Leu Pro Ser Gln Ile Cys Ala Phe Arg Gly 275 280 285 Val Leu Thr Arg Ser Thr Ser Arg Ala Ser Asp Gln Ala Asp Thr Ala 290 295 300 Thr Pro Arg Leu Phe Asn Tyr Tyr Trp His Ile Gln Leu Ala Asn Leu 305 310 315 320 Asn Gly Thr Pro Tyr Asp Pro Ala Glu Asp Ile Pro Gly Pro Leu Gly 325 330 335 Thr Pro Asp Phe Arg Gly Lys Val Phe Gly Val Ala Cys Gln Arg Asn 340 345 350 Pro Asp Cys Thr Thr Arg Ala His Glu Ala Lys Val Asp Thr Thr Ala 355 360 365 Gly Arg Phe Thr Pro Lys Leu Gly Ser Leu Glu Ile Ser Thr Glu Ser 370 375 380 Gly Asp Phe Asp Gln Asn Gln Pro Thr Arg Phe Thr Pro Val Gly Ile 385 390 395 400 Gly Val Asp His Glu Ala Asp Phe Gln Gln Trp Ser Leu Pro Asp Tyr 405 410 415 Ser Gly Gln Phe Thr His Asn Met Asn Leu Ala Pro Ala Val Ala Pro 420 425 430 Asn Phe Pro Gly Glu Gln Leu Leu Phe Phe Arg Ser Gln Leu Pro Ser 435 440 445 Ser Gly Gly Arg Ser Asn Gly Ile Leu Asp Cys Leu Val Pro Gln Glu 450 455 460 Trp Val Gln His Phe Tyr Gln Glu Ser Ala Pro Ala Gln Thr Gln Val 465 470 475 480 Ala Leu Val Arg Tyr Val Asn Pro Asp Thr Gly Arg Val Leu Phe Glu 485 490 495 Ala Lys Leu His Lys Leu Gly Phe Met Thr Ile Ala Lys Asn Gly Asp 500 505 510 Ser Pro Ile Thr Val Pro Pro Asn Gly Tyr Phe Arg Phe Glu Ser Trp 515 520 525 Val Asn Pro Phe Tyr Thr Leu Ala Pro Met Gly Thr Gly Asn Gly Arg 530 535 540 Arg Arg Ile Gln 545 <210> 31 <211> 540 <212> PRT <213> Norovirus <400> 31 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Thr Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Ser Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Pro Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Ser Ala 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Ile Ala Gly Thr Gln Glu Tyr Thr Met Asn Leu Ala 290 295 300 Ser Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Val Leu Thr Gln 325 330 335 Thr Thr Arg Arg Asp Gly Ser Thr Arg Gly His Lys Ala Thr Val Ser 340 345 350 Thr Gly Ser Val His Phe Thr Pro Lys Leu Gly Arg Ile Gln Phe Ser 355 360 365 Thr Asp Thr Ser Asn Asp Phe Glu Thr Gly Gln Asn Thr Arg Phe Thr 370 375 380 Pro Val Gly Val Val Gln Asp Gly Ser Thr Thr His Gln Asn Glu Pro 385 390 395 400 Gln Gln Trp Val Leu Pro Asn Tyr Ser Gly Arg Asp Ser His Asn Val 405 410 415 His Leu Ala Pro Ala Val Ala Pro Ser Phe Pro Gly Glu Gln Leu Leu 420 425 430 Phe Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asn 435 440 445 Leu Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu 450 455 460 Ala Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro 465 470 475 480 Asp Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr 485 490 495 Val Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala 515 520 525 Pro Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 540 <210> 32 <211> 537 <212> PRT <213> Norovirus <400> 32 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Thr Ala 1 5 10 15 Ser Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Ser Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Ser Thr 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Gly Ile Thr Arg Ile Gly Gln Ser Glu Ser Tyr Lys Met Asn Leu Ala 290 295 300 Ser Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Lys Gly Arg Ile Arg Gly Leu Leu Thr Gln 325 330 335 Thr Thr Lys Gly Ala Gly Ser Thr Arg Gly His Lys Ala Thr Val Leu 340 345 350 Thr Gly Gly Ser Asp Phe Thr Pro Lys Leu Gly Thr Val Arg Phe Asp 355 360 365 Thr Lys Ser Ile Asp Phe Glu Asn Asn Gln Asn Thr Lys Phe Thr Pro 370 375 380 Val Gly Val Val Gln Asp Gly Asn Asn His Asp Glu Pro Thr Gln Trp 385 390 395 400 Val Leu Pro Asn Tyr Ser Gly Pro Asp Thr His Asn Val His Leu Ala 405 410 415 Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe Phe Arg 420 425 430 Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Lys Met Glu Leu Asp Cys 435 440 445 Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Ala Ala Pro 450 455 460 Ala Gln Thr Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp Thr Gly 465 470 475 480 Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Val Thr Val 485 490 495 Ala His Thr Gly Asp His Asp Leu Val Ile Pro Pro Asn Gly Tyr Phe 500 505 510 Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro Met Gly 515 520 525 Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 33 <211> 540 <212> PRT <213> Norovirus <400> 33 Met Lys Met Ala Ser Asn Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Leu Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Ser Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Ser Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Ile Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Thr Asn Glu Pro Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Glu Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Ser Ser 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Ile Ala Gly Ser Arg Asn Tyr Thr Met Asn Leu Ala 290 295 300 Ser Ile Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Met Leu Thr Gln 325 330 335 Thr Thr Arg Gly Glu Gly Ser Thr Arg Ala His Arg Ala Thr Val Tyr 340 345 350 Thr Gly Ser Ala Pro Phe Thr Pro Lys Leu Gly Ser Val Gln Phe Thr 355 360 365 Thr Asp Thr Asp Asn Asp Phe Asp Ala Asn Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Ile Gln Asp Gly Asp Thr Ala His Arg Asn Glu Pro 385 390 395 400 Gln Gln Trp Val Leu Pro Ser Tyr Ser Gly Arg Asn Val Gln Asn Val 405 410 415 His Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu 420 425 430 Phe Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asp 435 440 445 Leu Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu 450 455 460 Ala Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro 465 470 475 480 Asp Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr 485 490 495 Val Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala 515 520 525 Pro Met Gly Asn Gly Ala Gly Arg Arg Arg Ala Leu 530 535 540 <210> 34 <211> 540 <212> PRT <213> Norovirus <400> 34 Met Lys Met Ala Ser Asn Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Ser Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Ser 210 215 220 Lys Pro Phe Ser Val Pro Val Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ala Thr Leu Asp Lys Leu Phe Thr Gly Pro Ser Ser Thr 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Met Ile Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Leu Arg Asp Ser Pro Ile Tyr Thr Met Asn Leu Ala 290 295 300 Ser Pro Asn Trp Asn Asn Tyr Asp Ser Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Val Leu Thr Gln 325 330 335 Thr Thr Lys Gly Glu Gly Ser Thr Arg Gly His Arg Ala Thr Val Tyr 340 345 350 Val Gly Ser Ala Asn Tyr Thr Pro Lys Leu Gly Lys Val Gln Phe Glu 355 360 365 Thr Asn Thr Thr Asn Asp Leu Tyr Ala His Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Val Gln Gly Gly Glu Ser Ala His Arg Ser Glu Pro 385 390 395 400 Gln Gln Trp Val Leu Pro Gly Tyr Ser Gly Arg Asp Thr Pro Asn Val 405 410 415 His Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu 420 425 430 Phe Phe Arg Ser Thr Ile Pro Gly Cys Gly Gly His Pro Asn Met Asp 435 440 445 Leu Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu 450 455 460 Ala Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro 465 470 475 480 Asp Thr Ser Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr 485 490 495 Val Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala 515 520 525 Pro Met Gly Asn Gly Thr Gly Arg Lys Arg Ala Ile 530 535 540 <210> 35 <211> 539 <212> PRT <213> Norovirus <400> 35 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Thr Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Ser Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Pro Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Val Pro Ile Leu Thr Val Gly Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Asn Leu Glu Arg Leu Phe Thr Gly Pro Ser Ser Ala 245 250 255 Asn Val Val Gln Pro Gln Asn Gly Arg Cys Thr Ile Asp Gly Glu Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Ser Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Ile Gly Ser Thr His His Trp Thr Met Asn Leu Ala 290 295 300 Ser Pro Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Thr Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile His Gly Met Leu Thr Gln 325 330 335 Thr Thr Gln Gly Asn Gly Ser Thr Arg Gly His Arg Ala Thr Val Tyr 340 345 350 Val Gly Ser Ala Glu Phe Thr Pro Lys Leu Gly Lys Val Gln Phe Lys 355 360 365 Thr Glu Thr Asp His Asp Leu Ala Ile Arg Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Ile Gln Glu Ser Asp His His Arg Asp Glu Pro Gln 385 390 395 400 Gln Trp Arg Leu Pro Asn Tyr Ser Gly Ala Asn Thr Phe Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Asn Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Leu Pro Gly Cys Gly Gly His Pro Asn Met Asp Leu 435 440 445 Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Ser Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Val 485 490 495 Thr Val Ala His Thr Gly Gln Tyr Asp Leu Val Leu Pro Ser Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 36 <211> 539 <212> PRT <213> Norovirus <400> 36 Met Lys Met Ala Ser Asn Asp Ala Ser Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Val Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Lys Asp Pro Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Glu Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Ser 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Gly Ala 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Leu Thr His Phe Thr Gly Thr Ser Glu Tyr Ala Met Asn Leu Ala 290 295 300 Ser Gln Asn Trp Asp Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Ala Pro Asp Phe Val Gly Lys Ile Arg Gly Met Leu Thr Gln 325 330 335 Thr Thr Arg Arg Asp Gly Ser Thr Arg Gly His Arg Ala Thr Leu Ser 340 345 350 Thr Gly Ser Ala His Phe Thr Pro Lys Leu Gly Asn Ile Arg Phe Ser 355 360 365 Thr Asp Thr Asn Asn Asp Phe Glu Ala Gly Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Phe Gln Glu Gly Asp Asn His Gln Asn Glu Pro Gln 385 390 395 400 Gln Trp Val Leu Pro Asn Tyr Ser Gly Ala Thr Ala His Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Ala Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Met Pro Gly Cys Gly Gly Tyr Pro Asn Met Asn Leu 435 440 445 Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Ser Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Val 485 490 495 Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 37 <211> 539 <212> PRT <213> Norovirus <400> 37 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Thr Ala 1 5 10 15 Asn Leu Val Pro Glu Ala Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Ala Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Leu 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Met Ile Pro Leu Pro Asp 145 150 155 160 Ile Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Pro Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Val Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Asn Pro Phe Ser Val Pro Ile Leu Thr Ile Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Ser Ala 245 250 255 Leu Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Thr Thr Lys Thr His Thr Tyr Gln Met Asn Leu Ala 290 295 300 Ala Gln Asn Trp Asn Ser Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Val Leu Thr Gln 325 330 335 Thr Thr Lys Gly Asn Gly Ser Thr Arg Ala His Lys Ala Thr Val Tyr 340 345 350 Thr Gly Ser Ala Glu Phe Thr Pro Lys Leu Gly Arg Ile Gln Leu Phe 355 360 365 Thr Asp Thr Asp Asn Asp Leu Glu Ala Asn Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Ile Gln Asp Gly Asp Thr His Gln Asn Glu Pro Gln 385 390 395 400 Gln Trp Val Leu Pro Ser Tyr Ser Gly Arg Asn Asn His Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asn Leu 435 440 445 Asp Cys Leu Leu Pro Gln Glu Trp Val Gln Tyr Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Val 485 490 495 Thr Val Ala His Thr Gly His His Asp Leu Phe Ile Pro Pro Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Ser Pro Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 38 <211> 538 <212> PRT <213> Norovirus <400> 38 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Ile Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Lys Asp Ser Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Val Pro Val Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Phe Thr Gly Pro Ser Ser Ala 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Ala Val Asn Ile Cys Thr Phe Arg Gly 275 280 285 Asp Val Thr His Val Ala Gly Asp Thr Phe Ala Met Asn Leu Ala Ser 290 295 300 Leu Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Thr Pro Ala Pro Leu 305 310 315 320 Gly Thr Pro Asp Phe Val Gly Arg Ile His Gly Met Leu Thr Gln Thr 325 330 335 Thr Arg Ser Asp Gly Ala Thr Arg Ala His Lys Ala Thr Val Ser Thr 340 345 350 Gly Gly Ala Asp Phe Thr Pro Lys Leu Gly Ser Val Arg Tyr Ser Thr 355 360 365 Asp Thr Ser Ser Asp Leu Glu Val Arg Glu Asn Thr Lys Phe Thr Pro 370 375 380 Ile Gly Val Leu His Ser Ser Gly Gly His Arg Ala Glu Pro Asp Gln 385 390 395 400 Trp Arg Leu Pro Glu Tyr Ser Gly Arg Asn Val His Asn Val His Leu 405 410 415 Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe Phe 420 425 430 Arg Ser Thr Met Pro Gly Cys Gly Gly Tyr Pro Asn Met Asp Leu Asp 435 440 445 Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Ala Ala 450 455 460 Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp Thr 465 470 475 480 Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Val Thr 485 490 495 Val Ala His Thr Gly Pro His Asp Leu Val Ile Pro Pro Asn Gly Tyr 500 505 510 Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro Met 515 520 525 Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 39 <211> 539 <212> PRT <213> Norovirus <400> 39 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Val Ile Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser His Asp Ser Thr Leu 165 170 175 Lys Leu Ile Ala Val Leu Tyr Thr Pro Leu Arg Thr Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Val Glu Glu Met Ser Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Lys Leu Tyr Thr Gly Pro Ser Ser Ala 245 250 255 Phe Val Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Val Leu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Ala Val Asn Ile Cys Asn Phe Arg Gly 275 280 285 Asp Val Thr His Ile Val Gly Ser His Glu Thr Thr Met Asn Leu Ala 290 295 300 Ser Gln Asn Trp Ser Asn Tyr Asp Pro Thr Gln Lys Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro His Phe Val Gly Lys Ile Gln Gly Leu Leu Thr Gln 325 330 335 Thr Thr Arg Ala His Gly Ser Thr Arg Ala His Lys Ala Thr Val Ser 340 345 350 Thr Gly Ser Val His Phe Thr Pro Lys Leu Gly Ser Val Gln Phe Thr 355 360 365 Thr Asp Thr Asn Asn Asp Phe Gln Thr Gly Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Ile Gln Asp Gly Asp His His Gln Asn Glu Pro Gln 385 390 395 400 Gln Trp Val Leu Pro Asn Tyr Ser Gly Arg Thr Gly His Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asn Leu 435 440 445 Asp Cys Leu Leu Pro His Glu Trp Val Leu His Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ser Gly Tyr Ile 485 490 495 Thr Val Ala His Thr Gly Pro Phe Asp Leu Gly Ile Pro Pro Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Thr Gly Arg Arg Arg Ala Leu 530 535 <210> 40 <211> 539 <212> PRT <213> Norovirus <400> 40 Met Lys Met Ala Ser Asn Asp Ala Ser Pro Ser Asp Gly Ser Thr Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Asn Ser Ser Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asp Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Ala Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Gly Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ser Asn Asp Ser Thr Ile 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Asn Cys Ser Arg Val Pro Ala Val Pro 245 250 255 Leu Ser Ser Asn His Lys Met Gln Cys Thr Thr Asp Gly Val Leu Leu 260 265 270 Gly Thr Thr Gln Leu Ser Pro Val Asn Ile Cys Thr Phe Arg Gly Asp 275 280 285 Val Thr His Ile Pro Gly Thr Arg Thr Tyr Arg Met Asn Leu Ala Ser 290 295 300 Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro Leu 305 310 315 320 Gly Thr Pro Asp Phe Val Gly Lys Ile Gln Gly Met Leu Thr Gln Thr 325 330 335 Thr Lys Gly Asp Gly Ser Thr Arg Gly His Lys Ala Thr Val Ser Thr 340 345 350 Gly Ser Val Asp Phe Thr Pro Lys Leu Gly Ser Val Gln Phe Ala Thr 355 360 365 Asp Thr Asp Asn Asp Phe Glu Thr Gly Gln Asn Thr Arg Phe Thr Pro 370 375 380 Val Gly Val Ile Gln Asp Gly Ser Ser Thr His Arg Asn Glu Pro Gln 385 390 395 400 Gln Trp Val Leu Pro Asp Tyr Ser Gly Arg Thr Val His Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Met Pro Gly Cys Ser Gly Tyr Pro Asn Met Asp Leu 435 440 445 Asp Cys Leu Leu Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ser Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Lys Ala Gly Tyr Val 485 490 495 Thr Val Ala His Thr Gly Gln His Asp Leu Val Ile Pro Pro Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Ala Gly Arg Arg Arg Ala Leu 530 535 <210> 41 <211> 539 <212> PRT <213> Norovirus <400> 41 Met Lys Met Ala Ser Ser Asp Ala Asn Pro Ser Asp Gly Ser Ser Ala 1 5 10 15 Asn Leu Val Pro Glu Val Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ala Ile Ala Ala Pro Val Ala Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Gly Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Ile Leu Trp Ser Ala Pro 65 70 75 80 Leu Ser Pro Asp Leu Asn Pro Tyr Leu Ser His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Phe Glu Val Gln Val Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Val Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Thr Glu Gly Leu Ser Pro Ser Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Tyr His Tyr Asn Gln Ala Asn Asp Ser Thr Leu 165 170 175 Lys Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Ile Phe Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Val Leu Thr Val Glu Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Leu Glu Arg Leu Phe Thr Gly Pro Ser Thr Ala 245 250 255 PheValValGlnProGlnAsnGlyArgCysThrThrAspGlyValLeu 260 265 270 Leu Gly Thr Thr Gln Leu Ser Ala Val Asn Ile Cys Asn Phe Arg Gly 275 280 285 Glu Val Asn His Ile Ala Gly Thr His Asp Tyr Thr Met Arg Leu Thr 290 295 300 Ser Gln Asn Trp Asn Asn Tyr Asp Pro Thr Glu Glu Ile Pro Ala Pro 305 310 315 320 Leu Gly Thr Pro Asp Phe Val Gly Arg Ile Gln Gly Val Leu Thr Gln 325 330 335 Thr Thr Arg Ser Asp Gly Ser Thr Arg Ser His Lys Ala Thr Val Ser 340 345 350 Thr Gly Ser Val His Phe Thr Pro Lys Leu Gly Ser Val Gln Phe Thr 355 360 365 Thr Asp Thr Thr Asn Asp Leu Asn Ala Gly Gln Asn Thr Lys Phe Thr 370 375 380 Pro Val Gly Val Glu Gln Thr Ser Gly Asp His Gln Ser Glu Pro Gln 385 390 395 400 Gln Trp Thr Leu Pro Asn Tyr Ser Gly Thr Pro Asn His Asn Val His 405 410 415 Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu Phe 420 425 430 Phe Arg Ser Thr Leu Pro Gly Cys Gly Gly Tyr Pro Asn Met Asn Leu 435 440 445 Asp Cys Leu Leu Pro Gln Glu Trp Val Leu His Phe Tyr Gln Glu Ala 450 455 460 Ala Pro Ala Gln Ser Asp Val Ala Leu Leu Arg Phe Val Asn Pro Asp 465 470 475 480 Thr Gly Arg Val Leu Phe Glu Cys Lys Leu His Arg Ser Gly Phe Ile 485 490 495 Thr Val Ala His Ser Gly Ser His Asp Leu Val Ile Pro Pro Asn Gly 500 505 510 Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Thr Leu Ala Pro 515 520 525 Met Gly Asn Gly Ser Gly Arg Arg Arg Val Val 530 535 <210> 42 <211> 540 <212> PRT <213> Norovirus <400> 42 Met Lys Met Ala Ser Asn Asp Ala Thr Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ser Asn Asn Glu Ala Met Ala Leu Glu Pro Val 20 25 30 Val Gly Ala Ser Leu Ala Ala Pro Val Thr Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Thr Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Val Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Met Glu Val Gln Val Met Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro Tyr Phe 115 120 125 Pro Val Glu Asn Leu Ser Pro Ser Gln Ile Thr Met Phe Pro His Val 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Leu Leu Pro Met Pro Asp 145 150 155 160 Val Arg Ser Thr Leu Phe His Phe Asn Gln Lys Asp Glu Pro Lys Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Ile Leu Thr Arg Pro Ser Pro 195 200 205 Glu Phe Asp Phe Thr Tyr Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Val Leu Thr Leu Gly Glu Leu Ser Asn Ser 225 230 235 240 Arg Phe Pro Leu Ser Ile Asp Glu Met Val Thr Ser Pro Asn Glu Ser 245 250 255 Ile Val Val Gln Pro Gln Asn Gly Arg Val Thr Leu Asp Gly Glu Leu 260 265 270 Leu Gly Thr Thr Gln Leu Gln Ala Cys Asn Ile Cys Ser Ile Arg Gly 275 280 285 Lys Val Thr Gly Gln Val Pro Asn Glu Gln His Met Trp Asn Leu Gln 290 295 300 Ile Thr Asn Leu Asn Gly Thr Gln Phe Asp Pro Thr Asp Asp Val Pro 305 310 315 320 Ala Pro Leu Gly Val Pro Asp Phe Ala Gly Glu Val Phe Gly Val Leu 325 330 335 Ser Gln Arg Asn Arg Gly Glu Ser Asn Pro Ala Asn Arg Ala His Asp 340 345 350 Ala Val Val Ala Thr Tyr Ser Asp Lys Tyr Thr Pro Lys Leu Gly Leu 355 360 365 Val Gln Ile Gly Thr Trp Asn Thr Asn Asp Val Glu Asn Gln Pro Thr 370 375 380 Lys Phe Thr Pro Ile Gly Leu Asn Glu Val Ala Asn Gly His Arg Phe 385 390 395 400 Glu Gln Trp Thr Leu Pro Arg Tyr Ser Gly Ala Leu Thr Leu Asn Met 405 410 415 Asn Leu Ala Pro Ala Val Ala Pro Leu Phe Pro Gly Glu Arg Leu Leu 420 425 430 Phe Phe Arg Ser Tyr Val Pro Leu Lys Gly Gly Phe Gly Asn Pro Ala 435 440 445 Ile Asp Cys Leu Val Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu 450 455 460 Ser Ala Pro Ser Leu Gly Asp Val Ala Leu Val Arg Tyr Val Asn Pro 465 470 475 480 Asp Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Lys Gly Gly Phe 485 490 495 Leu Thr Val Ser Ser Thr Ser Thr Gly Pro Val Val Val Pro Ala Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu Ala 515 520 525 Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Phe Gln 530 535 540 <210> 43 <211> 547 <212> PRT <213> Norovirus <400> 43 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Ala Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Ile Ala Ala Pro Val Val Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Glu Asn Phe Val Gln Ala Pro Gln Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Met Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ser His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Met Gln Val Gln Val Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Val Lys Asn Ile Ser Ala Ala Gln Ile Thr Met Cys Pro His Val 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Leu Pro Leu Pro Asp 145 150 155 160 Ile Arg Asn Arg Phe Phe His Tyr Asn Gln Glu Asn Thr Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Ser Gly Glu 180 185 190 Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ala Pro Asp 195 200 205 Phe Glu Phe Thr Phe Leu Val Pro Pro Thr Val Glu Ser Lys Thr Lys 210 215 220 Pro Phe Thr Leu Pro Ile Leu Thr Leu Gly Glu Leu Ser Asn Ser Arg 225 230 235 240 Phe Pro Ala Pro Ile Asp Met Leu Tyr Thr Asp Pro Asn Glu Gly Ile 245 250 255 Val Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Asp Gly Thr Leu Gln 260 265 270 Gly Thr Thr Gln Leu Val Pro Thr Gln Ile Cys Ala Phe Arg Gly Thr 275 280 285 Leu Ile Gly Gln Thr Ser Arg Ser Ser Asp Ser Thr Asp Ser Ala Pro 290 295 300 Arg Arg Arg Asp His Pro Leu His Val Gln Leu Lys Asn Leu Asp Gly 305 310 315 320 Thr Gln Tyr Asp Pro Thr Asp Glu Val Pro Ala Val Leu Gly Ala Ile 325 330 335 Asp Phe Lys Gly Thr Val Phe Gly Val Ala Ser Gln Arg Asp Val Ser 340 345 350 Gly Gln Gln Val Gly Ala Thr Arg Ala His Glu Val His Ile Asn Thr 355 360 365 Thr Asp Pro Arg Tyr Thr Pro Lys Leu Gly Ser Ile Leu Ile His Ser 370 375 380 Glu Ser Asp Asp Phe Val Thr Gly Gln Pro Val Arg Phe Thr Pro Ile 385 390 395 400 Gly Met Gly Asp Asn Asp Trp His Gln Trp Glu Leu Pro Asp Tyr Ser 405 410 415 Gly His Leu Thr Leu Asn Met Asn Leu Ala Pro Ala Val Ala Pro Ala 420 425 430 Phe Pro Gly Glu Arg Ile Leu Phe Phe Arg Ser Met Val Pro Ser Ala 435 440 445 Gly Gly Tyr Gly Ser Gly Gln Ile Asp Cys Leu Ile Pro Gln Glu Trp 450 455 460 Val Gln His Phe Tyr Gln Glu Ala Ala Pro Ser Gln Ser Ala Val Ala 465 470 475 480 Leu Ile Arg Tyr Val Asn Pro Asp Thr Gly Arg Asn Ile Phe Glu Ala 485 490 495 Lys Leu His Arg Glu Gly Phe Ile Thr Val Ala Asn Ser Gly Asn Asn 500 505 510 Pro Ile Val Val Pro His Asn Gly Tyr Phe Arg Phe Glu Ala Trp Val 515 520 525 Asn Gln Phe Tyr Thr Leu Thr Pro Met Gly Thr Gly Gln Gly Arg Arg 530 535 540 Arg Asn Gln 545 <210> 44 <211> 540 <212> PRT <213> Norovirus <400> 44 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Val Met Pro Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Leu Ala Thr Pro Val Val Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Ala Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asp Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly His Ala Gly Gly Met Glu Val Gln Ile Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Ile Phe Ala Ala Ile Pro Pro Gly Phe 115 120 125 Pro Tyr Glu Asn Leu Ser Pro Ser Gln Ile Thr Met Cys Pro His Val 130 135 140 Ile Ile Asp Val Arg Gln Leu Glu Pro Val Leu Leu Pro Met Pro Asp 145 150 155 160 Ile Arg Asn Asn Phe Phe His Tyr Asn Gln Gly Asn Asp Pro Lys Leu 165 170 175 Arg Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Lys Pro Ser Pro 195 200 205 Asp Phe Glu Phe Thr Phe Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Gln Phe Thr Leu Pro Ile Leu Lys Ile Ser Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Val Pro Val Glu Met Met Tyr Thr Ala Arg Asn Glu Asn 245 250 255 Gln Val Val Gln Pro Gln Asn Gly Arg Val Thr Leu Asp Gly Glu Leu 260 265 270 Leu Gly Thr Thr Pro Leu Leu Ala Val Asn Ile Cys Lys Phe Lys Gly 275 280 285 Glu Val Ile Ala Lys Asn Gly Asp Val Arg Ser Tyr Arg Met Asp Met 290 295 300 Glu Ile Thr Asn Thr Asp Gly Thr Pro Ile Asp Pro Thr Glu Asp Thr 305 310 315 320 Pro Gly Pro Ile Gly Ser Pro Asp Phe Gln Gly Ile Leu Phe Gly Val 325 330 335 Ala Ser Gln Arg Asn Lys Asn Glu Gln Asn Pro Ala Thr Arg Ala His 340 345 350 Glu Ala Asn Ile Asn Thr Gly Gly Asp Gln Tyr Ala Pro Lys Leu Ala 355 360 365 Gln Val Lys Phe Phe Ser Glu Ser Gln Asp Phe Glu Val His Gln Pro 370 375 380 Thr Val Phe Thr Pro Val Gly Val Ala Gly Asp Thr Ser His Pro Phe 385 390 395 400 Arg Gln Trp Val Leu Pro Arg Tyr Gly Gly His Leu Thr Asn Asn Thr 405 410 415 His Leu Ala Pro Ala Val Ala Pro Leu Phe Pro Gly Glu Gln Ile Leu 420 425 430 Phe Phe Arg Ser Gln Ile Pro Ser Ser Gly Gly His Glu Leu Gly Tyr 435 440 445 Met Asp Cys Leu Val Pro Gln Glu Trp Val Gln His Phe Tyr Gln Glu 450 455 460 Ala Ala Thr Ala Gln Ser Glu Val Ala Leu Ile Arg Phe Ile Asn Pro 465 470 475 480 Asp Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Lys Gln Gly Phe 485 490 495 Ile Thr Val Ala His Thr Gly Asp Asn Pro Ile Val Met Pro Pro Asn 500 505 510 Gly Tyr Phe Arg Phe Glu Ala Trp Val Asn Gln Phe Tyr Ser Leu Ala 515 520 525 Pro Val Gly Thr Gly Asn Gly Arg Arg Arg Ile Gln 530 535 540 <210> 45 <211> 537 <212> PRT <213> Norovirus <400> 45 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn His Glu Val Met Ala Ile Glu Pro Val 20 25 30 Ala Gly Ala Ser Leu Ala Ala Pro Val Val Gly Gln Leu Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Ala Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ala Pro Gly Glu Phe Leu Leu Asp Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly His Ala Gly Gly Met Glu Val Gln Ile Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Val Ile Pro Pro Gly Phe 115 120 125 Pro Tyr Glu Asn Leu Ser Pro Ala Gln Leu Thr Met Cys Pro His Val 130 135 140 Val Val Asp Val Arg Gln Leu Glu Pro Ile Leu Leu Pro Met Pro Asp 145 150 155 160 Ile Arg Asn Thr Phe Phe His Tyr Asn Gln Ser Asn Gly Pro Lys Leu 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ala Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Glu Phe Asn Phe Leu Val Pro Pro Ser Val Glu Ser Lys Thr 210 215 220 Lys Ala Phe Thr Leu Pro Ile Leu Lys Ile Ser Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Val Asp Gln Met Tyr Thr Ser Arg Asn Glu Asn 245 250 255 Val Val Val Gln Pro Gln Asn Gly Arg Val Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Leu Gln Pro Val Ser Ile Cys Gly Phe Arg Gly 275 280 285 Thr Leu Gln Thr Arg Leu Ala Asp Gln Pro Asn Tyr Thr Tyr Gln Val 290 295 300 His Leu Glu Asn Leu Asp Gly Ser Pro Val Asp Pro Thr Asp Glu Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Gln Ala Gln Leu Phe Gly Val 325 330 335 Val Ser Gln Arg Ser Ser Asp Asn Ala Thr Arg Ala His Glu Ala Arg 340 345 350 Val Asn Thr Asn Asp Pro Thr Phe Ala Pro Gln Ile Ala Gln Val Arg 355 360 365 Phe Lys Ser Pro Ser His Asp Phe Phe Asp Asn Glu Pro Ile Lys Phe 370 375 380 Thr Pro Val Gly Ile Ser Val Asp Ser Glu Asn Ser Tyr Asn Gln Trp 385 390 395 400 Leu Leu Pro Arg Tyr Gly Gly His Leu Thr Asn Asn Thr His Leu Ala 405 410 415 Pro Ser Val Ser Pro Met Phe Pro Gly Glu Gln Ile Leu Phe Phe Arg 420 425 430 Ser Phe Met Pro Gly Ala Ser Gly His Thr Asp Gly Ala Ile Asp Cys 435 440 445 Leu Leu Pro Gln Glu Trp Val Ala His Phe Tyr Gln Glu Ala Ala Thr 450 455 460 Ala Gln Thr Asp Val Ala Leu Ile Arg Phe Val Asn Pro Asp Thr Gly 465 470 475 480 Arg Val Leu Phe Glu Gly Lys Leu His Lys Gln Gly Phe Ile Thr Ile 485 490 495 Ser Asn Ser Gly Asp His Pro Ile Val Met Pro Ala Asn Gly Tyr Phe 500 505 510 Arg Phe Glu Ala Trp Val Asn Gln Phe Tyr Ser Leu Ala Pro Val Gly 515 520 525 Thr Gly Ser Gly Arg Arg Arg Ile Gln 530 535 <210> 46 <211> 535 <212> PRT <213> Norovirus <400> 46 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Val Asn Asn Glu Thr Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Ile Ala Ala Pro Leu Thr Gly Gln Asn Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Leu Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Val Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Leu Val Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Leu Glu Asn Ile Ser Pro Gly Gln Ile Thr Met Phe Pro His Val 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Leu Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Asn Phe Phe His Tyr Asn Gln Gln Asn Glu Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Asp Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Gly Glu Leu Thr Asn Ser 225 230 235 240 Arg Phe Pro Val Pro Ile Asp Glu Leu Tyr Thr Ser Pro Asn Glu Ser 245 250 255 Leu Val Val Gln Pro Gln Asn Gly Arg Cys Ala Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Leu Pro Thr Ala Ile Cys Ser Phe Arg Gly 275 280 285 Arg Ile Asn Gln Lys Val Ser Gly Glu Asn His Val Trp Asn Met Gln 290 295 300 Ile Thr Asn Ile Asn Gly Thr Pro Phe Asp Pro Thr Glu Asp Val Pro 305 310 315 320 Ala Pro Leu Gly Thr Pro Asp Phe Ser Gly Lys Leu Phe Gly Val Leu 325 330 335 Ser Gln Arg Asp His Asp Asn Ala Cys Arg Ser His Asp Ala Val Ile 340 345 350 Ala Thr Asn Ser Ala Lys Phe Thr Pro Lys Leu Gly Ala Ile Gln Ile 355 360 365 Gly Thr Trp Glu Gln Asp Asp Val His Ile Asn Gln Pro Thr Lys Phe 370 375 380 Thr Pro Val Gly Leu Phe Glu Ser Glu Gly Phe Asn Gln Trp Thr Leu 385 390 395 400 Pro Asn Tyr Ser Gly Ala Leu Thr Leu Asn Met Gly Leu Ala Pro Pro 405 410 415 Val Ala Pro Thr Phe Pro Gly Glu Gln Ile Leu Phe Phe Arg Ser His 420 425 430 Ile Pro Leu Lys Gly Gly Val Ala Asp Pro Val Ile Asp Cys Leu Leu 435 440 445 Pro Gln Glu Trp Ile Gln His Leu Tyr Gln Glu Ser Ala Pro Ser Gln 450 455 460 Thr Asp Val Ala Leu Ile Arg Phe Thr Asn Pro Asp Thr Gly Arg Val 465 470 475 480 Leu Phe Glu Ala Lys Leu His Arg Ser Gly Tyr Ile Thr Val Ala Asn 485 490 495 Thr Gly Ser Arg Pro Ile Val Val Pro Ala Asn Gly Tyr Phe Arg Phe 500 505 510 Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu Ala Pro Met Gly Thr Gly 515 520 525 Asn Gly Arg Arg Arg Val Gln 530 535 <210> 47 <211> 528 <212> PRT <213> Norovirus <400> 47 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Ser Leu Val Pro Glu Ala Ile Asn Glu Thr Met Pro Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Ile Ala Ala Pro Val Ala Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Thr Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Ile Pro Pro Asn Phe 115 120 125 Pro Val Asp Met Ile Ser Pro Ala Gln Ile Thr Met Leu Pro His Leu 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Met Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Val Phe Tyr His Phe Asn Asn Gln Pro Gln Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Thr Pro 195 200 205 Asp Phe Glu Phe Ile Tyr Leu Val Pro Pro Ser Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Ser Glu Leu Thr Asn Ser 225 230 235 240 Arg Phe Pro Ile Pro Ile Glu Gln Leu Tyr Thr Ala Pro Asn Glu Asn 245 250 255 Asn Val Val Gln Cys Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Leu Ser Ser Ala Val Cys Ser Tyr Arg Gly 275 280 285 Arg Thr Val Ala Asn Arg Gly Asp Asn Trp Asp Gln Asn Leu Leu Gln 290 295 300 Leu Thr Tyr Pro Ser Gly Ala Ser Tyr Asp Pro Thr Asp Glu Val Pro 305 310 315 320 Ala Pro Leu Gly Thr Gln Asp Phe Ser Gly Ile Leu Tyr Gly Val Leu 325 330 335 Thr Gln Asp Asn Val Ser Glu Gly Thr Gly Glu Ala Lys Asn Ala Lys 340 345 350 Gly Val Tyr Ile Ser Thr Thr Ser Gly Lys Phe Thr Pro Lys Ile Gly 355 360 365 Ser Ile Gly Leu His Ser Ile Thr Glu Asn Val His Pro Asn Gln Gln 370 375 380 Ser Arg Phe Thr Pro Val Gly Val Ala Gln Asn Glu Asn Thr Pro Phe 385 390 395 400 Gln Gln Trp Val Leu Pro His Tyr Ala Gly Ala Leu Ala Leu Asn Thr 405 410 415 Asn Leu Ala Pro Ala Val Ala Pro Thr Phe Pro Gly Glu Gln Leu Leu 420 425 430 Phe Phe Arg Ser Arg Val Pro Cys Val Gln Gly Leu Arg Gly Gln Asp 435 440 445 Ala Phe Ile Asp Cys Leu Leu Pro Gln Glu Trp Val Asn His Phe Tyr 450 455 460 Gln Glu Ala Ala Pro Ser Gln Ala Asp Val Ala Leu Ile Arg Tyr Val 465 470 475 480 Asn Pro Asp Thr Gly Arg Thr Leu Phe Glu Ala Lys Leu His Arg Ser 485 490 495 Gly Phe Ile Thr Val Ser His Thr Gly Ala Tyr Pro Leu Val Val Pro 500 505 510 Pro Asn Gly His Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser 515 520 525 <210> 48 <211> 536 <212> PRT <213> Norovirus <400> 48 Met Lys Met Ala Ser Asn Asp Ala Thr Pro Ser Asp Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Ala Ser Ile Ala Ala Pro Val Val Gly Gln Gln Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Ala Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Leu Leu Leu Asp Leu Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Tyr Leu Ala His Leu Ala Arg Met Tyr 85 90 95 Asn Gly His Ala Gly Gly Met Glu Val Gln Ile Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Ile Pro Pro Ser Phe 115 120 125 Pro Tyr Glu Asn Leu Ser Pro Ala Gln Leu Thr Met Cys Pro His Val 130 135 140 Ile Val Asp Val Arg Gln Leu Glu Pro Val Leu Leu Pro Met Pro Asp 145 150 155 160 Ile Arg Asn Val Phe Tyr His Tyr Asn Gln Asn Asn Ser Pro Lys Leu 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ala Asn Asn Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Gln Phe Thr Phe Leu Val Pro Pro Thr Val Glu Ser Lys Thr 210 215 220 Lys Asn Phe Thr Leu Pro Val Leu Arg Val Ser Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Val Val Leu Asp Gln Met Tyr Thr Ser Arg Asn Glu Asn 245 250 255 Ile Ile Val Gln Pro Gln Asn Gly Arg Cys Thr Thr Asp Gly Glu Leu 260 265 270 Leu Gly Thr Thr Thr Leu Gln Ser Val Ser Ile Cys Asn Phe Arg Gly 275 280 285 Thr Met Gln Ala Lys Leu Asn Glu Gln Pro Arg Tyr Gln Leu Gln Leu 290 295 300 Thr Asn Leu Asp Gly Ser Pro Ile Asp Pro Thr Asp Asp Met Pro Ala 305 310 315 320 Pro Leu Gly Thr Pro Asp Phe Gln Ala Met Leu Tyr Gly Val Ala Ser 325 330 335 Gln Arg Ser Ser Arg Asp Asn Ala Thr Arg Ala His Asp Ala Gln Ile 340 345 350 Asp Thr Ala Gly Asp Thr Phe Ala Pro Lys Ile Gly Gln Val Arg Phe 355 360 365 Lys Ser Ser Ser Asp Asp Phe Asp Leu His Asp Pro Thr Lys Phe Thr 370 375 380 Pro Ile Gly Val Asn Val Asp Asp Gln His Pro Phe Arg Gln Trp Ser 385 390 395 400 Leu Pro Asn Tyr Gly Gly His Leu Ala Leu Asn Asn His Leu Ala Pro 405 410 415 Ala Val Thr Pro Leu Phe Pro Gly Glu Gln Ile Leu Phe Phe Arg Ser 420 425 430 His Ile Pro Ser Ala Gly Gly His Thr Asp Gly Ala Ile Asp Cys Leu 435 440 445 Leu Pro Gln Glu Trp Ile Glu His Phe Tyr Gln Glu Ala Ala Pro Ser 450 455 460 Gln Ser Asp Ile Ala Leu Val Arg Phe Ile Asn Pro Asp Thr Gly Arg 465 470 475 480 Val Leu Leu Glu Ala Lys Leu His Lys Gln Gly Phe Leu Thr Val Ala 485 490 495 Ala Ser Gly Asp His Pro Ile Val Met Pro Thr Asn Gly Tyr Phe Arg 500 505 510 Phe Glu Ala Trp Val Asn Pro Phe Tyr Thr Leu Ala Pro Val Gly Thr 515 520 525 Gly Ser Gly Arg Arg Arg Ile Gln 530 535 <210> 49 <211> 538 <212> PRT <213> Norovirus <400> 49 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Gly Asn Asn Glu Thr Leu Pro Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Ile Ala Ala Pro Val Thr Gly Gln Asn Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Thr Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Val Glu Phe Leu Ser Pro Ala Gln Ile Thr Met Leu Pro His Ile 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Met Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Thr Phe Phe His Tyr Asn Asn Gln Pro Asn Ser Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Thr Pro 195 200 205 Asp Phe Glu Phe Thr Tyr Leu Val Pro Pro Ser Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Ser Leu Pro Ile Leu Thr Leu Ser Glu Leu Thr Asn Ser 225 230 235 240 Arg Phe Pro Val Pro Ile Asp Ser Leu Phe Thr Ala Gln Asn Asn Val 245 250 255 Leu Gln Val Gln Cys Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Leu Pro Ser Gly Ile Cys Ala Phe Arg Gly 275 280 285 Arg Val Thr Ala Glu Thr Asp Asn Pro Asp Lys Trp His Met Gln Leu 290 295 300 Gln Asn Leu Asn Gly Thr Thr Tyr Asp Pro Thr Asp Asp Val Pro Ala 305 310 315 320 Pro Leu Gly Thr Pro Asp Phe Lys Gly Val Val Phe Gly Val Ala Ser 325 330 335 Gln Arg Asn Val Gly Asn Asp Ala Pro Gly Ser Thr Arg Ala His Glu 340 345 350 Ala Val Ile Ser Thr Tyr Ser Pro Lys Phe Val Pro Lys Leu Gly Ser 355 360 365 Val Asn Phe Arg Ser Asn Asp Asp Asp Phe Gln Leu Gln Pro Thr Arg 370 375 380 Phe Thr Pro Val Gly Ile Asn Asp Asp Gly Asn His Pro Phe Arg Gln 385 390 395 400 Trp Glu Leu Pro Asp Tyr Ser Gly Val Leu Thr Leu Asn Met Asn Leu 405 410 415 Ala Pro Pro Val Ala Pro Asn Phe Pro Gly Glu Gln Leu Leu Leu Phe 420 425 430 Arg Ser Phe Val Pro Cys Ser Gly Gly Tyr Asn Gln Gly Ile Ile Asp 435 440 445 Cys Leu Ile Pro Gln Glu Trp Ile Gln His Phe Tyr Gln Glu Ser Ala 450 455 460 Pro Ser Gln Ser Asp Val Ala Leu Ile Arg Tyr Val Asn Pro Asp Thr 465 470 475 480 Gly Arg Thr Leu Phe Glu Ala Lys Leu His Arg Ser Gly Tyr Ile Thr 485 490 495 Val Ala His Ser Gly Asp Tyr Pro Leu Val Val Pro Ala Asn Gly Tyr 500 505 510 Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu Ala Pro Met 515 520 525 Gly Thr Gly Asn Gly Arg Arg Arg Ala Gln 530 535 <210> 50 <211> 540 <212> PRT <213> Norovirus <400> 50 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Thr 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Thr Leu Pro Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Ile Ala Ala Pro Val Thr Gly Gln Asn Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Thr Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Val Glu Phe Leu Ser Pro Ala Gln Ile Thr Met Leu Pro His Leu 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Met Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Thr Phe Phe His Tyr Asn Asn Gln Pro Ala Asn Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Thr Pro 195 200 205 Asp Phe Glu Phe Thr Tyr Leu Val Pro Pro Ser Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Ser Leu Pro Ile Leu Thr Ile Ser Glu Leu Thr Asn Ser 225 230 235 240 Arg Phe Pro Ala Pro Ile Asp Ser Leu Phe Thr Ala Gln Asn Asn Asn 245 250 255 Leu Asn Val Gln Cys Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Leu Pro Ser Gly Ile Cys Ala Phe Arg Gly 275 280 285 Arg Leu Thr Ala Asp Val Asp Gly Ser His Asp Asp Arg Trp His Met 290 295 300 Gln Leu Thr Asn Leu Asn Gly Thr Pro Phe Asp Pro Thr Glu Asp Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Thr Gly Leu Leu Phe Gly Val 325 330 335 Ala Ser Gln Arg Asn Val Gly Ser Asn Pro Asn Thr Thr Arg Ala His 340 345 350 Glu Ala Val Ile Ser Thr Thr Ser Ser Gln Phe Val Pro Lys Leu Gly 355 360 365 Ser Val Asn Phe Gly Ser Thr Ser Thr Asp Phe Gln Leu Gln Gln Pro 370 375 380 Thr Lys Phe Thr Pro Val Gly Ile Lys Ile Glu Ser Gly His Glu Phe 385 390 395 400 Asp Gln Trp Ala Leu Pro Arg Tyr Ser Gly His Leu Thr Leu Asn Met 405 410 415 Asn Leu Ala Pro Pro Ile Ala Pro Asn Phe Pro Gly Glu Gln Leu Leu 420 425 430 Phe Phe Arg Ser Asn Val Pro Cys Ala Gly Gly Val Ser Asp Gly Val 435 440 445 Ile Asp Cys Leu Leu Pro Gln Glu Trp Ile Gln His Phe Tyr Gln Glu 450 455 460 Ser Ala Pro Ser Gln Ser Asp Val Ala Leu Ile Arg Tyr Val Asn Pro 465 470 475 480 Asp Thr Gly Arg Thr Leu Phe Glu Ala Lys Leu His Arg Thr Gly Tyr 485 490 495 Ile Thr Val Ala His Ser Gly Asp Tyr Pro Leu Val Val Pro Ser Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu Ala 515 520 525 Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Val Gln 530 535 540 <210> 51 <211> 540 <212> PRT <213> Norovirus <400> 51 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Thr Glu Thr Leu Pro Leu Glu Pro Val 20 25 30 Ala Gly Ala Ala Ile Ala Ala Pro Val Thr Gly Gln Asn Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Val Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Met Asn Leu Glu 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Tyr Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Leu Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Phe Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Val Asp Met Leu Ser Pro Ala Gln Ile Thr Met Leu Pro His Leu 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Met Ile Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Val Phe Tyr His Phe Asn Asn Gln Pro Ala Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Gly 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Thr Pro 195 200 205 Asp Phe Glu Phe Thr Tyr Leu Val Pro Pro Ser Val Glu Ser Lys Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Gly Glu Leu Thr Asn Ser 225 230 235 240 Arg Phe Pro Ala Pro Ile Asp Gln Leu Tyr Thr Ser Pro Asn Ala Asp 245 250 255 Val Val Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Leu Thr Thr Ala Ile Cys Ser Tyr Arg Gly 275 280 285 Thr Thr Ser Asn Pro Thr Ser Asp Tyr Trp Asp Asp His Leu Leu His 290 295 300 Leu Val His Pro Asn Gly Ala Thr Tyr Asp Pro Thr Glu Asp Val Pro 305 310 315 320 Ala Pro Phe Gly Thr Gln Asp Phe Arg Gly Ile Leu Tyr Gly Val Leu 325 330 335 Thr Gln Asn Thr Gln Asn Pro Arg Asp Glu Val Ser Asn Ser Arg Gly 340 345 350 Ile Tyr Ile Ser Ser Thr Ser Asp Lys Phe Thr Pro Lys Leu Gly Thr 355 360 365 Ile Gly Leu His Gln Val Gln Gly Asp Thr Ala Ser Asn Gln Gln Ser 370 375 380 Lys Phe Thr Pro Val Gly Ile Ala Val Asn Gln Asn Thr Pro Phe Lys 385 390 395 400 Gln Trp Glu Leu Pro Asn Tyr Ser Gly Ala Leu Thr Leu Asn Thr Asn 405 410 415 Leu Ala Pro Ala Val Gly Pro Asn Phe Pro Gly Glu Gln Ile Leu Phe 420 425 430 Phe Arg Ser Asn Val Pro Ser Val Gln Gly Asn His Pro Thr Gln Glu 435 440 445 Ile Asp Cys Leu Ile Pro Gln Glu Trp Ile Ser His Phe Tyr Gln Glu 450 455 460 Ser Ala Pro Ser Gln Ser Asp Val Ala Leu Val Arg Tyr Val Asn Pro 465 470 475 480 Asp Thr Gly Arg Thr Ile Phe Glu Ala Lys Leu His Arg Gln Gly Phe 485 490 495 Ile Thr Ile Ala Ala Thr Gly Ser Asn Pro Val Val Val Pro Pro Asn 500 505 510 Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ala Leu Ala 515 520 525 Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Ala Gln 530 535 540 <210> 52 <211> 541 <212> PRT <213> Norovirus <400> 52 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Thr Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Gly Ala Ile Ala Ala Pro Leu Thr Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Arg Asn Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Ile Ser Pro Arg Asn Ser Pro Gly Glu Ile Leu Leu Asn Met Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Phe Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Phe Ala Gly Gly Met Glu Val Gln Val Leu Met Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Val Ile Phe Ala Ala Ile Pro Pro His Phe 115 120 125 Pro Val Glu Asn Leu Ser Pro Pro Gln Ile Thr Met Phe Pro His Ile 130 135 140 Ile Ile Asp Val Arg Thr Leu Glu Pro Val Leu Leu Pro Met Pro Asp 145 150 155 160 Val Arg Asn Gln Phe Phe His Tyr Asn Gln Val Asn Glu Pro Arg Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Thr 180 185 190 Glu Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Glu Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Leu Pro Ile Leu Thr Ile Gly Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Ala Pro Ile Asp Met Leu Tyr Thr Ser Pro Asn Asp Asn 245 250 255 Val Val Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Ser Thr Gln Leu Val Pro Ala Asn Val Cys Ala Phe Lys Gly 275 280 285 Lys Ile Thr Ala Arg Ile Val Asp Gln Ala Ala His Gln Trp His Met 290 295 300 Gln Ile Asp Asn Pro Asn Gly Thr Leu Phe Asp Pro Thr Glu Asp Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Lys Ala Lys Ile Phe Gly Val 325 330 335 Ile Ser Gln Arg Asn Asp Tyr Asn Asp Gly Ser Gln Gly Pro Ala Asn 340 345 350 Arg Ala His Asp Ala Val Val Pro Thr Thr Ser Ala Lys Phe Thr Pro 355 360 365 Lys Leu Gly Ser Ile Leu Val Gly Thr Trp Glu Asn Asn Asp Ile Glu 370 375 380 Thr Gln Pro Ser Lys Phe Thr Pro Val Gly Leu Leu Glu Met Asn Asp 385 390 395 400 Phe Asn Gln Trp Ser Leu Pro Asn Tyr Ser Gly Ala Leu Thr Leu Asn 405 410 415 Met Gly Leu Ala Pro Ala Val Phe Pro Thr Phe Pro Gly Glu Gln Ile 420 425 430 Leu Phe Phe Arg Ser Phe Ile Pro Leu Lys Gly Gly His Gly Asn Pro 435 440 445 Ala Ile Asp Cys Leu Leu Pro Gln Glu Trp Ile Gln His Phe Tyr Gln 450 455 460 Glu Ser Ala Pro Ser Gln Thr Ser Val Ala Leu Ile Arg Tyr Val Asn 465 470 475 480 Pro Asp Thr Gly Arg Val Leu Phe Glu Gly Lys Leu His Arg Gln Gly 485 490 495 Phe Ile Thr Ile Ala Lys Ser Gly Asp Gly Pro Ile Val Val Pro Pro 500 505 510 Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu 515 520 525 Ala Pro Met Gly Asn Gly Asn Gly Arg Arg Arg Ile Gln 530 535 540 <210> 53 <211> 542 <212> PRT <213> Norovirus <400> 53 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Asn Leu Val Pro Glu Ala Asn Lys Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Gly Ala Ile Ala Ala Pro Leu Thr Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Met Asn Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Ile Ser Pro Arg Asn Ser Pro Gly Glu Val Leu Leu Asn Leu Glu 65 70 75 80 Leu Gly Pro Asp Leu Asn Pro Phe Leu Ala His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Val Glu Val Gln Val Ile Met Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Val Ile Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Val Asp Asn Leu Ser Pro Pro Gln Val Thr Met Phe Pro His Val 130 135 140 Ile Val Asp Val Arg Thr Phe Glu Pro Ile Leu Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Ser Phe Tyr His Tyr Asn Gln Val Asn Asp Ser Arg Met 165 170 175 Arg Leu Ile Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Ser 180 185 190 Asp Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Thr Pro 195 200 205 Asp Phe Glu Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Ser Val Pro Ile Leu Thr Ile Gly Glu Met Thr Asn Ser 225 230 235 240 Arg Phe Pro Leu Pro Ile Asp Met Leu Tyr Thr Ser Pro Thr Glu Asn 245 250 255 Ile Val Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Glu Gly Glu Leu 260 265 270 Leu Gly Thr Thr Gln Leu Val Thr Pro Asn Ile Cys Ala Leu Arg Gly 275 280 285 Glu Ile Arg Gly His Glu Gly Ser Gly Asp Asn His Lys Trp His Phe 290 295 300 Met Val Arg Ser Pro Asn Gly Ala Ala Phe Asp Pro Thr Glu Asp Val 305 310 315 320 Pro Ala Pro Leu Gly Thr Pro Asp Phe Ile Gly Asp Val Phe Gly Val 325 330 335 Leu Ser Gln Arg Asn Arg Asn Thr Asp Ser Gly Gln Ser Gly Pro Ala 340 345 350 Asn Arg Ser His Asp Ala Val Val Ser Thr Arg Asp Ser Arg Phe Thr 355 360 365 Pro Lys Leu Gly Ser Val Met Ile Ala Thr Trp Glu Thr Ser Asp Ile 370 375 380 Gln Asp Gln Pro Thr Arg Phe Thr Pro Val Gly Leu Glu Asn Pro Asp 385 390 395 400 His Tyr Asn Gln Trp Gln Leu Pro Asn Tyr Ser Gly Ala Leu Thr Leu 405 410 415 Asn Met Gly Leu Ala Pro Ser Val Phe Pro Thr Tyr Pro Gly Glu Gln 420 425 430 Ile Leu Phe Phe Arg Ser Tyr Ile Pro Leu Lys Gly Gly Tyr Gly Asp 435 440 445 Ser His Ile Asp Cys Leu Val Pro Gln Glu Trp Ile Gln His Phe Tyr 450 455 460 Gln Glu Ser Ala Pro Ser Gln Thr Asp Val Ala Leu Ile Arg Tyr Val 465 470 475 480 Asn Pro Glu Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Arg Gln 485 490 495 Gly Tyr Ile Thr Val Ala Arg Ser Gly Ser Ser Pro Ile Asn Val Pro 500 505 510 Ala Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser 515 520 525 Leu Ala Pro Met Gly Thr Gly Asn Gly Arg Arg Arg Ile Gln 530 535 540 <210> 54 <211> 541 <212> PRT <213> Norovirus <400> 54 Met Lys Met Ala Ser Asn Asp Ala Ala Pro Ser Asn Asp Gly Ala Ala 1 5 10 15 Gly Leu Val Pro Glu Ile Asn Asn Glu Val Met Ala Leu Glu Pro Val 20 25 30 Ala Gly Gly Ala Ile Ala Ala Pro Leu Thr Gly Gln Thr Asn Val Ile 35 40 45 Asp Pro Trp Ile Arg Thr Asn Phe Val Gln Ala Pro Asn Gly Glu Phe 50 55 60 Thr Ile Ser Pro Arg Asn Ser Pro Gly Glu Val Leu Leu Asn Met Glu 65 70 75 80 Leu Gly Pro Glu Leu Asn Pro Phe Leu Gly His Leu Ser Arg Met Tyr 85 90 95 Asn Gly Tyr Ala Gly Gly Ile Glu Val Gln Val Leu Met Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Val Ile Phe Ala Ala Val Pro Pro His Phe 115 120 125 Pro Val Glu Asn Leu Ser Pro Pro Gln Val Thr Met Phe Pro His Ile 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Ile Leu Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Asn Gln Phe Phe His Tyr Ser Gln Val Asp Glu Pro Lys Met 165 170 175 Arg Leu Val Ala Met Leu Tyr Thr Pro Leu Arg Ser Asn Gly Ser Ala 180 185 190 Glu Asp Val Phe Thr Val Ser Cys Arg Val Leu Thr Arg Pro Ser Pro 195 200 205 Asp Phe Glu Phe Asn Tyr Leu Val Pro Pro Thr Val Glu Ser Arg Thr 210 215 220 Lys Pro Phe Thr Val Pro Ile Leu Thr Ile Gly Glu Met Ser Asn Ser 225 230 235 240 Arg Phe Pro Ala Pro Ile Asp Met Leu Tyr Thr Ser Pro Asn Asp Asn 245 250 255 Gln Asn Val Gln Pro Gln Asn Gly Arg Cys Thr Leu Asp Gly Glu Leu 260 265 270 Gln Gly Thr Thr Gln Leu Val Pro Ser Gly Val Cys Ala Phe Arg Gly 275 280 285 Arg Ile Thr Gly His Glu Gly Ser Glu Gln Asn Gln Trp His Met Gln 290 295 300 Leu Thr Asn Leu Asn Gly Thr Pro Phe Asp Pro Thr Glu Asp Ile Pro 305 310 315 320 Ala Pro Leu Gly Thr Pro Asp Phe Lys Gly Glu Ile Phe Gly Phe Ile 325 330 335 Ser Gln Arg Asn Ala Gln Asn Asp Pro Gly Gln Ser Gln Pro Ala Asn 340 345 350 Arg Ala His Asp Ala Val Val Ser Thr Arg Ala Pro Lys Phe Thr Pro 355 360 365 Lys Leu Gly Ser Val Met Ile Gly Thr Trp Val Asn Ser Asp Ile Glu 370 375 380 Asn Gln Pro Ser Lys Phe Thr Pro Val Gly Leu Asn Ser Asn Glu Asn 385 390 395 400 Phe Arg Gln Trp Glu Leu Pro Asp Tyr Ser Gly Val Leu Thr Leu Asn 405 410 415 Met Gly Leu Ala Pro Val Val His Pro Thr Tyr Pro Gly Glu Gln Ile 420 425 430 Leu Phe Phe Arg Ser Tyr Ile Pro Leu Lys Gly Gly His Gly Asn Pro 435 440 445 Ala Ile Asp Cys Leu Leu Pro Gln Glu Trp Ile Gln His Phe Tyr Gln 450 455 460 Glu Ser Ala Pro Ser Gln Thr Asp Val Ala Leu Leu Arg Tyr Val Asn 465 470 475 480 Pro Asp Thr Gly Arg Val Leu Phe Glu Ala Lys Leu His Arg Gln Gly 485 490 495 Tyr Ile Thr Ile Ala Lys Ser Gly Asp Gly Pro Ile Val Val Pro Pro 500 505 510 Asn Gly Tyr Phe Arg Phe Asp Ser Trp Val Asn Gln Phe Tyr Ser Leu 515 520 525 Ala Pro Met Gly Asn Gly Asn Gly Arg Arg Arg Val Gln 530 535 540 <210> 55 <211> 556 <212> PRT <213> Norovirus <400> 55 Met Lys Met Ala Ser Ser Asp Ala Ala Pro Ser Thr Asp Gly Ala Gly 1 5 10 15 Asn Leu Val Pro Glu Ser Gln Gln Glu Val Leu Pro Leu Ala Pro Val 20 25 30 Ala Gly Ala Ala Leu Ala Ala Pro Val Val Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Lys Glu Asn Phe Val Gln Ala Pro Gln Gly Glu Phe 50 55 60 Thr Val Ser Pro Lys Asn Ser Pro Gly Glu Ile Leu Val Asn Leu Glu 65 70 75 80 Leu Gly Pro Lys Leu Asn Pro Tyr Leu Asp His Leu Ser Arg Met Tyr 85 90 95 Asn Ser Tyr Ala Gly Gly Ile Asp Val Met Val Val Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Val Leu Ile Ala Ala Ile Pro Pro Asn Phe 115 120 125 Pro Val Glu Gly Val Ser Ala Ser Gln Ala Thr Gln Phe Pro His Val 130 135 140 Ile Ile Asp Val Arg Thr Leu Asp Pro Val Arg Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Ser Thr Phe Phe His Tyr Thr Asn Asp Thr Glu Pro Lys Met 165 170 175 Arg Leu Val Ile Trp Leu Tyr Thr Pro Leu Arg Thr Asn Gly Ser Gly 180 185 190 Asp Asp Ser Phe Thr Val Ser Gly Arg Ile Leu Thr Arg Pro Ser Gln 195 200 205 Asp Phe Glu Phe Ala Phe Leu Ile Pro Pro Thr Val Glu Thr Lys Thr 210 215 220 Thr Pro Phe Ser Val Pro Gly Phe Ser Val Gln Glu Met Ser Asn Ser 225 230 235 240 Arg Trp Pro Ala Ala Ile Ser Ala Met Val Val Arg Gly Asn Glu Pro 245 250 255 Gln Val Val Gln Phe Gln Asn Gly Arg Ala His Leu Asp Gly Met Leu 260 265 270 Leu Gly Thr Thr Pro Val Ser Pro Asn Tyr Ile Ala Ser Tyr Arg Gly 275 280 285 Ile Ser Thr Gly Asn Ser Arg Ser Ala Ser Ser Glu Ala Asp Glu Arg 290 295 300 Ala Val Gly Ser Phe Asp Val Trp Val Arg Leu Gln Glu Pro Asp Gly 305 310 315 320 Gln Pro Tyr Asp Ile Phe Gly Lys Gln Pro Ala Pro Ile Gly Thr Pro 325 330 335 Asp Phe Lys Ala Val Ile Val Gly Phe Ala Ala Arg Pro Leu Thr Ser 340 345 350 Gly Ser Tyr Ala Asn Glu Ala Tyr Val Asn Thr Thr Ala Ser Asp Tyr 355 360 365 Ala Pro Ala Thr Gly Asn Met Arg Phe Thr Val Arg Asn Gly Gly Thr 370 375 380 Gly His Ile Ser Ala Asn Lys Tyr Trp Glu Phe Lys Ser Phe Gly Val 385 390 395 400 Glu Gly Glu Arg His Thr Asp Ile Gln Tyr Gln Glu Tyr Glu Leu Pro 405 410 415 Asp Tyr Ser Gly Gln Val Ala Ser Asn His Asn Leu Ala Pro Pro Val 420 425 430 Ala Pro Arg Met Pro Gly Glu Ser Leu Leu Leu Phe Gln Ser Asn Met 435 440 445 Pro Val Trp Asp Asp Gly His Gly Glu Ser Thr Pro Lys Lys Ile His 450 455 460 Cys Leu Leu Pro Gln Glu Phe Ile Gly His Phe Phe Asp Arg Gln Ala 465 470 475 480 Pro Ser Leu Gly Asp Ala Ala Leu Leu Arg Tyr Val Asn Gln Glu Thr 485 490 495 Asn Arg Val Leu Phe Glu Cys Lys Leu Tyr Arg Asp Gly Tyr Ile Thr 500 505 510 Val Ala Ala Ser Ser Gly Leu Leu Asp Phe Pro Leu Asp Gly Phe Phe 515 520 525 Arg Phe Asp Ser Trp Val Ser Ser Phe Tyr Ile Leu Ser Pro Val Gly 530 535 540 Ser Gly Gln Gly Arg Arg Gly Arg Val Arg Phe Gln 545 550 555 <210> 56 <211> 554 <212> PRT <213> Norovirus <400> 56 Met Lys Met Ala Ser Asn Asp Ala Pro Pro Ser Ser Asp Gly Ala Gly 1 5 10 15 Asn Leu Val Pro Glu Ser His Gln Glu Val Leu Pro Leu Ala Pro Val 20 25 30 Ala Gly Ala Glu Leu Ala Ala Pro Val Val Gly Gln Thr Asn Ile Ile 35 40 45 Asp Pro Trp Ile Lys Glu Asn Phe Val Gln Ala Pro Gln Gly Glu Phe 50 55 60 Thr Val Ser Pro Lys Asn Ala Pro Gly Glu Ile Leu Val Asn Leu Glu 65 70 75 80 Leu Gly Pro Asn Leu Asn Pro Tyr Leu Glu His Leu Ser Arg Met Tyr 85 90 95 Asn Ala Tyr Ala Gly Gly Ile Glu Val Glu Ile Ile Leu Ala Gly Asn 100 105 110 Ala Phe Thr Ala Gly Lys Ile Leu Ile Ala Ala Val Pro Pro Asn Phe 115 120 125 Pro Val Glu Ser Val Ser Ala Ser Gln Ala Thr Gln Phe Pro His Ala 130 135 140 Ile Val Asp Val Arg Thr Leu Glu Pro Val Arg Leu Pro Leu Pro Asp 145 150 155 160 Val Arg Ser Asn Phe Phe His Tyr Thr Thr Lys Asp Glu Pro Lys Met 165 170 175 Arg Leu Val Ile Trp Leu Tyr Thr Pro Leu Arg Thr Asn Gly Ser Gly 180 185 190 Asp Asp Ser Phe Thr Val Ser Gly Arg Leu Leu Thr Arg Pro Ser Met 195 200 205 Asp Phe Gln Phe Ser Phe Leu Val Pro Pro Thr Val Glu Thr Lys Thr 210 215 220 Val Leu Phe Thr Val Pro Gly Leu Thr Pro Gln Glu Met Ser Asn Ser 225 230 235 240 Arg Trp Pro Ala Gln Ile Ser Gly Met Val Val Arg Gly Asn Glu Pro 245 250 255 Gln Val Val Gln Phe Gln Asn Gly Arg Cys His Thr Asp Gly Thr Leu 260 265 270 Leu Gly Thr Thr Thr Val Ser Glu Gln Cys Ile Ala Gly Phe Val Gly 275 280 285 Thr Ser Thr Asn Thr Arg Ser Ala Thr Gly Ser Thr Thr Glu Thr Arg 290 295 300 Thr Gly Asp Thr Asp Leu Trp Leu Arg Leu Glu Glu Pro Asn Gly Gln 305 310 315 320 Pro Tyr Asp Ile Phe Gly Asp Gln Pro Ala Pro Leu Gly Thr Pro Asp 325 330 335 Phe Arg Ala Val Ile Val Gly Phe Ala Ser Arg Pro Gln Thr Gln Gly 340 345 350 Ser Tyr Met Asn Glu Ala Tyr Val Asn Thr Val Asp Ser His Phe Ala 355 360 365 Pro Ala Thr Gly Asn Thr Lys Ile Ile Leu Arg Arg Gly Gly Thr Gly 370 375 380 His Val Gly Gly Gly His Leu Trp Lys Phe Arg Pro Phe Gly Val Glu 385 390 395 400 Gly Gly Glu Gly Arg Val Ser Tyr Gln Glu Tyr Val Leu Pro Asn Tyr 405 410 415 Ser Gly Ala Thr Ala Ser Asn His Asn Leu Ala Pro Pro Val Ala Pro 420 425 430 Arg Met Pro Gly Glu Leu Leu Leu Leu Phe Glu Ser Asp Met Pro Val 435 440 445 Trp Asp Asp Gly His Gly Ala Ala Pro Ala Gln Lys Ile His Cys Leu 450 455 460 Leu Pro Gln Gln Phe Ile Thr His Phe Phe Asp Ser Gln Ala Pro Ala 465 470 475 480 Leu Ala Glu Ala Ala Leu Leu Arg Tyr Val His Pro Asp Ser Ser Arg 485 490 495 Val Leu Phe Glu Thr Lys Leu Tyr Arg Glu Gly Phe Met Val Val Ser 500 505 510 Ala Pro Thr Gly Arg Phe Asp Phe Pro Leu Asp Gly Tyr Phe Arg Phe 515 520 525 Asp Ser Trp Val Asn Ser Phe Tyr Val Leu Ser Pro Val Gly Ser Gly 530 535 540 Gln Gly Arg Arg Gly Arg Ser Lys Val Val 545 550 <210> 57 <211> 6 <212> PRT <213> artificial <220> <223> sequence stretch with variant amino acid residue <220> <221> VARIANT <222> (4)..(4) <223> Leu or Val <400> 57 Ala Ala Leu Xaa His Tyr 1 5 <210> 58 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> sequence stretch with variant amino acid residue <220> <221> VARIANT <222> (4)..(4) <223> Leu or Val <220> <221> VARIANT <222> (5)..(5) <223> Arg or Lys <400> 58 God God Leu Xaa Xaa Tyr 1 5 <210> 59 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> sequence stretch with variant amino acid residue <220> <221> variant <222> (4)..(4) <223> Leu or Val <220> <221> variant <222> (7)..(7) <223> Val, Leu or Ile <400> 59 Ala Ala Leu Xaa His Tyr Xaa Asp 1 5 <210> 60 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> sequence stretch with variant amino acid residue <220> <221> variant <222> (4)..(4) <223> Leu or Val <220> <221> variant <222> (5)..(5) <223> Arg or Lys <220> <221> variant <222> (7)..(7) <223> Val or Leu or Ile <400> 60 God God Leu Xa Xa Tyr Xa Asp 1 5 <210> 61 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> sequence stretch with variant amino acid residue <220> <221> VARIANT <222> (4)..(4) <223> Leu or Val <400> 61 God God Leu Xaa His 1 5

Claims

1. Norovirus genogroup I VP1 capsid protein, A capsid protein having an amino acid sequence as defined in any one of SEQ ID NOs: 6-21, except that the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg; or, wherein the protein has an amino acid sequence as defined in any one of SEQ ID NOs: 3-5.

2. Norovirus genogroup I VP1 capsid protein, (i) the amino acid sequence of the protein consists of or comprises at least 500 consecutive amino acid residues of the amino acid sequence of any one of SEQ ID NOs: 6 to 21, except that the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg; or (ii) the amino acid sequence of the protein consists of or comprises at least 500 amino acid residues and has at least 90% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 6 to 21; or (iii) the amino acid sequence of the protein has 1 to 50 deletions, substitutions, additions or insertions compared to the amino acid sequence of any one of SEQ ID NOs: 6 to 21; A capsid protein according to items (ii) and (iii), wherein the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg.

3. Norovirus genogroup I VP1 capsid protein, (i') the amino acid sequence of the protein consists of or comprises the amino acid sequence of residues 43 to 540 of SEQ ID NO: 3, 4 or 5; or (ii') the amino acid sequence of the protein has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 4 or 5; or (iii') the amino acid sequence of the protein has 1 to 50 deletions, substitutions, additions or insertions compared to the amino acid sequence of SEQ ID NO: 3, 4 or 5; The capsid protein according to items (ii') and (iii'), wherein the amino acid residue at the position corresponding to Arg472 in SEQ ID NO: 3 is Arg.

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