# US 10,500,269 B2 · Human rotavirus vaccine strains and diagnostics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,500,269 B2 - Document ID: US10500269B2 - Status: Granted - Kind: B2 - Application number: 15/956,662 - Filed: 2018-04-18 - Published: 2018-08-23 - Granted: 2019-12-10 - Earliest claimed: 2009-05-12 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services - Applicants: THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services - Inventors: Baoming Jiang; Roger I. Glass; Yuhuan Wang; Jon Gentsch - Web page: https://patentgrep.com/patent/US10500269B2 ## CPC - A61K 39/15: Reoviridae, e.g. calf diarrhea virus - A61K 39/12: Viral antigens - A61P 31/14: for RNA viruses - A61P 37/00: Drugs for immunological or allergic disorders - A61P 37/04: Immunostimulants - C07K 14/005: from viruses - C07K 16/10: RNA viruses - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - A61K 2039/5252: {inactivated (killed)} - A61K 2039/5254: {avirulent or attenuated} - A61K 2039/54: {characterised by the route of administration} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K 2039/55505: {Inorganic adjuvants} - C12N 2720/12334: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2720/12361: Methods of inactivation or attenuation - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract A vaccine composition and method of vaccination are provided useful for immunizing a subject against a rotavirus. The vaccines include rotavirus strains CDC-9 and CDC-66, fragments thereof, homologues thereof, or combinations thereof. Inventive vaccines may include a fragment of CDC-9, CDC-66, homologues thereof, or combinations thereof. Methods of inducing an immunological response are provided by administering an inventive vaccine. ## Claims ### Claim 1 An isolated VP4 protein, wherein a) the VP4 protein has greater than 95% identity to SEQ ID NO: 27, and wherein amino acid 51 is a aspartic acid, amino acid 331 is an phenylalanine, amino acid 364 is an isoleucine, amino acid 385 is a histidine, and amino acid 388 is a leucine; or b) the VP4 protein has greater than 95% identity to SEQ ID NO: 120, and wherein amino acid 254 is a lysine, amino acid 367 is an alanine, amino acid 385 is an asparagine, and amino acid 392 is a glycine. ### Claim 2 (depends on 1) The isolated VP4 protein of claim 1, wherein the VP4 protein comprises the amino acid sequence of SEQ ID NO: 27. ### Claim 3 (depends on 1) The isolated VP4 protein of claim 1, wherein the VP4 protein comprises the amino acid sequence of SEQ ID NO: 120. ### Claim 4 (depends on 1) An immunogenic composition comprising the VP4 protein of claim 1, and a pharmaceutically acceptable carrier. ### Claim 5 (depends on 4) A method of inducing an immune response to a rotavirus in a subject, comprising administering to the subject an immunogenic amount of the immunogenic composition of claim 4, thereby inducing the immunological response to the rotavirus. ### Claim 6 (depends on 5) The method of claim 5, wherein the immunogenic composition is administered orally, parenterally, intramuscularly, or intradermally. ### Claim 7 An immunogenic composition comprising: a live, attenuated human rotavirus or an inactivated human rotavirus, and an adjuvant that increases immunogenicity of the live, attenuated human rotavirus or inactivated human rotavirus, wherein said live, attenuated human rotavirus or inactivated human rotavirus comprises a NSP1, NSP2, NSP3, NSP4, NSP5, VP1, VP2, VP3, VP4, VP5, VP6 and VP7 protein, and wherein: a) the NSP1 protein has greater than 95% identity to SEQ ID NO: 2 or SEQ ID NO: 3; the NSP2 protein has greater than 95% identity to SEQ ID NO: 5; the NSP3 protein has greater than 95% identity to SEQ ID NO: 8; the NSP4 protein has greater than 95% identity to SEQ ID NO: 11; the NSP5 protein has greater than 95% identity to SEQ ID NO: 14 or SEQ ID NO: 15; the VP1 protein has greater than 95% identity to SEQ ID NO: 17; the VP2 protein has greater than 95% identity to SEQ ID NO: 20; the VP3 protein has greater than 95% identity to SEQ ID NO: 23; the VP4 protein has greater than 95% identity to SEQ ID NO: 26 or SEQ ID NO: 27; the VP6 protein has greater than 95% identity to SEQ ID NO: 29 or SEQ ID NO: 30; and the VP7 protein has greater than 95% identity to SEQ ID NO: 32; or b) the NSP1 protein has greater than 95% identity to SEQ ID NO: 71; the NSP2 protein has greater than 95% identity to SEQ ID NO: 77 or SEQ ID NO: 78; the NSP3 protein has greater than 95% identity to SEQ ID NO: 83; the NSP4 protein has greater than 95% identity to SEQ ID NO: 89; a NSP5 protein has greater than 95% identity to SEQ ID NO: 95 or SEQ ID NO: 96; the VP1 protein has greater than 95% identity to SEQ ID NO: 101 or SEQ ID NO: 102; the VP2 protein has greater than 95% identity to SEQ ID NO: 107; the VP3 protein has greater than 95% identity to SEQ ID NO: 113 or SEQ ID NO: 114; the VP4 protein has greater than 95% identity to SEQ ID NO: 119 or SEQ ID NO: 120; the VP6 protein has greater than 95% identity to SEQ ID NO: 125; and the VP7 protein has greater than 95% identity to SEQ ID NO: 131, wherein the immunogenic composition is formulated for intradermal or intramuscular administration to a subject. ### Claim 8 (depends on 7) The immunogenic composition of claim 7, wherein: the NSP1 protein comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3; the NSP2 protein comprises the amino acid sequence of SEQ ID NO: 5; the NSP3 protein comprises the amino acid sequence of SEQ ID NO: 8; the NSP4 protein comprises the amino acid sequence of SEQ ID NO: 11; the NSP5 protein comprises the amino acid sequence of SEQ ID NO: 14 or SEQ ID NO: 15; the VP1 protein comprises the amino acid sequence of SEQ ID NO: 17; the VP2 protein comprises the amino acid sequence of SEQ ID NO: 20; the VP3 protein comprises the amino acid sequence of SEQ ID NO: 23; the VP4 protein comprises the amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27; the VP6 protein comprises the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 30; and the VP7 protein comprises the amino acid sequence of SEQ ID NO: 32. ### Claim 9 (depends on 7) The immunogenic composition of claim 7, wherein: the NSP1 protein comprises the amino acid sequence of SEQ ID NO: 2; the NSP2 protein comprises the amino acid sequence of SEQ ID NO: 5; the NSP3 protein comprises the amino acid sequence of SEQ ID NO: 8; the NSP4 protein comprises the amino acid sequence of SEQ ID NO: 11; the NSP5 protein comprises the amino acid sequence of SEQ ID NO: 14; the VP1 protein comprises the amino acid sequence of SEQ ID NO: 17; the VP2 protein comprises the amino acid sequence of SEQ ID NO: 20; the VP3 protein comprises the amino acid sequence of SEQ ID NO: 23; the VP4 protein comprises the amino acid sequence of SEQ ID NO: 26; the VP6 protein comprises the amino acid sequence of SEQ ID NO: 29; and the VP7 protein comprises the amino acid sequence of SEQ ID NO: 32. ### Claim 10 (depends on 7) The immunogenic composition of claim 7, wherein: the NSP1 protein comprises the amino acid sequence of SEQ ID NO: 71; the NSP2 protein comprises the amino acid sequence of SEQ ID NO: 77 or SEQ ID NO: 78; the NSP3 protein comprises the amino acid sequence of SEQ ID NO: 83; the NSP4 protein comprises the amino acid sequence of SEQ ID NO: 89; the NSP5 protein comprises the amino acid sequence of SEQ ID-NO: 95 or SEQ ID: NO: 96; the VP1 protein comprises the amino acid sequence of SEQ ID NO: 101 or SEQ ID NO: 102; the VP2 protein comprises the amino acid sequence of SEQ ID NO: 107; the VP3 protein comprises the amino acid sequence of SEQ ID NO: 113 or SEQ ID NO: 114; the VP4 protein comprises the amino acid sequence of SEQ ID NO: 119 or SEQ ID NO: 120; the VP6 protein comprises the amino acid sequence of SEQ ID NO: 125; and the VP7 protein comprises the amino acid sequence of SEQ ID NO: 131. ### Claim 11 (depends on 7) A method of inducing an immunological response to a rotavirus in a subject, comprising administering intradermally or intramuscularly to the subject an immunogenic amount of the immunogenic composition of claim 7, thereby inducing the immunological response to the rotavirus. ### Claim 12 An immunogenic composition comprising a live, attenuated human rotavirus or an inactivated human rotavirus, wherein said live, attenuated human rotavirus or inactivated human rotavirus comprises a NSP1, NSP2, NSP3, NSP4, NSP5, VP1, VP2, VP3, VP4, VP5, VP6 and VP7 protein, wherein the immunogenic composition is formulated for intradermal or intramuscular administration to a subject, and wherein: a) the NSP1 protein has greater than 95% identity to SEQ ID NO: 3, and wherein amino acid 122 is an arginine; the NSP2 protein has greater than 95% identity to SEQ ID NO: 5; the NSP3 protein has greater than 95% identity to SEQ ID NO: 8; the NSP4 protein has greater than 95% identity to SEQ ID NO: 11; the NSP5 protein has greater than 95% identity to SEQ ID NO: 15, and wherein amino acid 45 is an isoleucine; the VP1 protein has greater than 95% identity to SEQ ID NO: 17; the VP2 protein has with greater than 95% identity to SEQ ID NO: 20; the VP3 protein has greater than 95% identity to SEQ ID NO: 23; the VP4 protein has greater than 95% identity to SEQ ID NO: 27, and wherein amino acid 51 is a aspartic acid, amino acid 331 is an phenylalanine, amino acid 364 is an isoleucine, amino acid 385 is a histidine, and amino acid 388 is a leucine; the VP6 protein has greater than 95% identity to SEQ ID NO: 30, and wherein amino acid 101 is a valine; and the VP7 protein has greater than 95% identity to SEQ ID NO: 32; or b) the NSP1 protein has greater than 95% identity to SEQ ID NO: 72; the NSP2 protein has greater than 95% identity to SEQ ID NO: 78, and wherein amino acid 142 is a tyrosine; the NSP3 protein has greater than 95% identity to SEQ ID NO: 84; the NSP4 protein has greater than 95% identity to SEQ ID NO: 90; the NSP5 protein has greater than 95% identity to SEQ ID NO: 96, and wherein amino acid 60 is a valine; the VP1 protein has greater than 95% identity to SEQ ID NO: 102, and wherein amino acid 141 is a serine; the VP2 protein has with greater than 95% identity to SEQ ID NO: 10; the VP3 protein has greater than 95% identity to SEQ ID NO: 114, and wherein amino acid 365 is a serine; the VP4 protein has greater than 95% identity to SEQ ID NO: 120, and wherein amino acid 254 is a lysine, amino acid 367 is an alanine, amino acid 385 is an asparagine, and amino acid 392 is a glycine; the VP6 protein has greater than 95% identity to SEQ ID NO: 126, and wherein amino acid 101 is an alanine; and the VP7 protein has greater than 95% identity to SEQ ID NO: 132. ### Claim 13 (depends on 12) The immunogenic composition of claim 12, comprising an adjuvant. ### Claim 14 (depends on 12) The immunogenic composition of claim 12, wherein the NSP1 protein comprises the amino acid sequence of SEQ ID NO: 3; the NSP2 protein comprises the amino acid sequence of SEQ ID NO: 5; the NSP3 protein comprises the amino acid sequence of SEQ ID NO: 8; the NSP4 protein comprises the amino acid sequence of SEQ ID NO: 11; the NSP5 protein comprises the amino acid sequence of SEQ ID NO: 15; the VP1 protein comprises the amino acid sequence of SEQ ID NO: 17; the VP2 protein comprises the amino acid sequence of SEQ ID NO: 20; the VP3 protein comprises the amino acid sequence of SEQ ID NO: 23; the VP4 protein comprises the amino acid sequence of SEQ ID NO: 27; the VP6 protein comprises the amino acid sequence of SEQ ID NO: 30; and the VP7 protein comprises the amino acid sequence of SEQ ID NO: 32. ### Claim 15 (depends on 12) The immunogenic composition of claim 12, wherein the NSP1 protein comprises the amino acid sequence of SEQ ID NO: 72; the NSP2 protein comprises the amino acid sequence of SEQ ID NO: 78; the NSP3 protein comprises the amino acid sequence of SEQ ID NO: 84; the NSP4 protein comprises the amino acid sequence of SEQ ID NO: 90; the NSP5 protein comprises the amino acid sequence of SEQ ID NO: 96; the VP1 protein comprises the amino acid sequence of SEQ ID NO: 102; the VP2 protein comprises the amino acid sequence of SEQ ID NO: 10; the VP3 protein comprises the amino acid sequence of SEQ ID NO: 114; the VP4 protein comprises the amino acid sequence of SEQ ID NO: 120; the VP6 protein comprises the amino acid sequence of SEQ ID NO: 126; and the VP7 protein comprises the amino acid sequence of SEQ ID NO: 132. ### Claim 16 (depends on 12) The immunogenic composition of claim 12, further comprising a pharmaceutically acceptable carrier. ### Claim 17 (depends on 12) A method of inducing an immunological response to a rotavirus in a subject, comprising administering to the subject an immunogenic amount of the immunogenic composition of claim 12, thereby inducing the immunological response to the rotavirus. ### Claim 18 (depends on 17) The method of claim 17, wherein the subject is human.