# US 2014/0154283 A1 · Identification of a west nile virus cd4 t cell epitope and use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154283 A1 - Document ID: US20140154283A1 - Status: Published application - Kind: A1 - Application number: 14/130,839 - Filed: 2012-07-11 - Published: 2014-06-05 - Earliest claimed: 2011-07-12 - Assignees: Department of Health and Human Services; The Government of the United States of America as represented by the Secretary of the - Inventors: Gwong-Jen J. Chang; Holly R. Hughes - Web page: https://patentgrep.com/patent/US20140154283A1 ## CPC - C07K 14/005: from viruses - A61K 2039/70: {Multivalent vaccine} - C12N 2770/24122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Described herein is the identification and of a potent West Nile virus (WNV) CD4 positive T cell epitope and its use for increasing the immunogenicity of heterologous flavivirus vaccines, such as dengue virus type 2 (DENV-2) DNA and virus-like particle (VLP) vaccines. Also described are methods for the identification of potent T cell epitopes to enhance immunogenicity of multivalent vaccines. ## Claims ### Claim 1 An isolated mutant flavivirus E-glycoprotein polypeptide, wherein the polypeptide comprises an isoleucine at position 474, a threonine at position 484, a valine at position 488 and a leucine at position 493, each numbered with reference to the West Nile virus E-glycoprotein polypeptide sequence of SEQ ID NO: 38, wherein the flavivirus is not West Nile virus. ### Claim 2 (depends on 1) The polypeptide of claim 1, wherein the flavivirus is DENV-2, DENV-1, DENV-3, DENV-4, Japanese encephalitis virus (JEV), Murray Valley encephalitis virus (MVEV), St. Louis encephalitis virus (SLEV), yellow fever virus (YFV) or tick-borne encephalitis virus (TBEV). ### Claim 3 (depends on 2) The polypeptide of claim 2, wherein the flavivirus is DENV-2. ### Claim 4 (depends on 1) The polypeptide of claim 1, wherein the amino acid sequence of the polypeptide comprises SEQ ID NO: 12, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 or SEQ ID NO: 31. ### Claim 5 (depends on 1) An isolated virus-like particle (VLP) comprising the polypeptide of claim 1. ### Claim 6 (depends on 5) The VLP of claim 5, further comprising a prM protein. ### Claim 7 (depends on 1) A recombinant nucleic acid molecule encoding the polypeptide of claim 1. ### Claim 8 (depends on 7) The recombinant nucleic acid molecule of claim 7, comprising the nucleotide sequence of SEQ ID NO: 10. ### Claim 9 (depends on 7) A vector comprising the recombinant nucleic acid molecule of claim 7. ### Claim 10 (depends on 9) An isolated cell comprising the vector of claim 9. ### Claim 11 (depends on 5) A composition comprising the VLP of claim 5 and a pharmaceutically acceptable carrier. ### Claim 12 (depends on 11) The composition of claim 11, further comprising an adjuvant. ### Claim 13 (depends on 5) A method of eliciting an immune response in a subject against a flavivirus, comprising administering to the subject a therapeutically effective amount of the VLP of claim 5, thereby eliciting an immune response in the subject against flavivirus. ### Claim 14 (depends on 13) The method of claim 13, wherein the subject is a mammal. ### Claim 15 (depends on 13) The method of claim 13, wherein the subject is human. ### Claim 16 A method of selecting a T cell epitope to enhance immunogenicity of a multivalent vaccine, wherein at least one component of the multivalent vaccine induces a weaker immune response compared with another component of the multivalent vaccine that induces a stronger immune response, the method comprising: (i) performing peptide scanning on the vaccine components to identify positive CD4 T cell epitopes or positive CD8 T cell epitopes, or both; (ii) comparing the positive T cell epitopes from the weaker vaccine component to the positive T cell epitopes from the stronger vaccine component to identify a candidate T cell epitope from the stronger vaccine component; and (iii) evaluating the ability of the candidate T cell epitope to bind human HLA alleles, wherein the candidate T cell epitope is selected if it is capable of binding to multiple different HLA alleles. ### Claim 17 (depends on 16) A method of enhancing immunogenicity of a multivalent vaccine, wherein at least one component of the multivalent vaccine induces a weaker immune response compared with another component of the multivalent vaccine that induces a stronger immune response, the method comprising introducing the T cell epitope selected by the method of claim 16 into the weaker component of the multivalent vaccine. ### Claim 18 (depends on 16) The method of claim 16, wherein the T cell epitope is a CD4 T cell epitope. ### Claim 19 (depends on 16) The method of claim 16, wherein the T cell epitope is a CD8 T cell epitope. ### Claim 20 (depends on 16) The method of claim 16, wherein the multivalent vaccine is a trivalent or tetravalent vaccine.