# US 10,611,801 B2 · Compositions and methods for preventing and treating Zika virus infection > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,611,801 B2 - Document ID: US10611801B2 - Status: Granted - Kind: B2 - Application number: 16/099,254 - Filed: 2017-06-09 - Published: 2019-05-16 - Granted: 2020-04-07 - Earliest claimed: 2016-06-09 - Assignees: Beth Israel Deaconess Medical Center, Inc. - Applicants: Beth Israel Deaconess Medical Center, Inc. - Inventors: Dan H. Barouch; Peter Abbink; Rafael Larocca - Web page: https://patentgrep.com/patent/US10611801B2 ## CPC - A61K 39/12: Viral antigens - A61P 31/14: for RNA viruses - C07K 14/005: from viruses - C07K 16/10: RNA viruses - A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) - A61K 2039/5256: {expressing foreign proteins} - A61K 2039/53: {DNA (RNA) vaccination} - A61K 2039/55: {characterised by the host/recipient, e.g. newborn with maternal antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C12N 2710/00043: viral genome or elements thereof as genetic vector - C12N 2770/24122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2770/24134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - 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 - 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) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The invention relates to immunogenic compositions and vaccines containing a ZIKV protein or a polynucleotide encoding a Zika virus (ZIKV) protein and uses thereof. The invention also provides methods of treating and/or preventing a ZiKV infection by administering an immunogenic composition or vaccine of the invention to a subject (e.g., a human). ## Claims ### Claim 1 An isolated nucleic acid molecule comprising: (i) a nucleotide sequence having at least 85% sequence identity to the sequence of any one of SEQ ID NOs: 1, 3, 5, 7, 9, and 11, or a complementary sequence thereof; and/or (ii) a nucleotide sequence that encodes a polypeptide having at least 85% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 2, 4, 6, 8, 10, and 12. ### Claim 2 An isolated polypeptide comprising an amino acid sequence having at least 85% sequence identity to the sequence of any one of SEQ ID NOs: 2, 4, 6, 8, 10, or 12. ### Claim 3 (depends on 1) A vector comprising one or more of the nucleic acid molecules of claim 1. ### Claim 4 (depends on 3) The vector of claim 3, wherein the vector is a mammalian, bacterial, or viral derived expression vector. ### Claim 5 (depends on 4) The vector of claim 4, wherein the vector is: (i) a viral vector derived from a virus selected from the group consisting of a retrovirus, adenovirus, adeno-associated virus, parvovirus, coronavirus, negative strand RNA viruses, orthomyxovirus, rhabdovirus, paramyxovirus, positive strand RNA viruses, picornavirus, alphavirus, double stranded DNA viruses, herpesvirus, Epstein-Barr virus, cytomegalovirus, fowlpox, and canarypox; (ii) an adenoviral vector derived from an adenovirus selected from the group consisting of Ad2, Ad5, Ad11, Ad12, Ad24, Ad26, Ad34, Ad35, Ad40, Ad48, Ad49, Ad50, Ad52, and Pan9; or (iii) an adenoviral vector derived from a human, chimpanzee, or rhesus adenovirus. ### Claim 6 (depends on 1) A composition comprising the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, or a vector comprising the nucleic acid molecule, wherein, optionally, the composition further comprises: (i) a pharmaceutically acceptable carrier, excipient, or diluent; and/or (ii) an adjuvant or an immunostimulatory agent. ### Claim 7 (depends on 6) An immunogenic composition comprising the composition of claim 6, wherein said immunogenic composition: (i) is capable of treating or reducing the risk of a ZIKV infection in a subject in need thereof; and/or (ii) elicits production of neutralizing anti-ZIKV antisera after administration to said subject. ### Claim 8 (depends on 2) An isolated antibody or an antigen-binding fragment thereof that specifically binds to the polypeptide of claim 2. ### Claim 9 (depends on 1, 8) The antibody of claim 8, wherein the antibody or antigen-binding fragment thereof is generated by immunizing a mammal with the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a composition comprising the nucleic acid molecule, polypeptide, or vector, and/or an immunogenic composition comprising the composition. ### Claim 10 (depends on 1) A method of producing anti-ZIKV antibodies, comprising administering to a subject an amount of at least one of the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a composition comprising the nucleic acid molecule, polypeptide or vector, and/or an immunogenic composition comprising the composition, wherein the amount is sufficient to elicit production of neutralizing anti-ZIKV antisera after administration to said subject. ### Claim 11 (depends on 10) An isolated anti-ZIKV antibody produced by the method of claim 10, wherein the isolated anti-ZIKV antibody binds to an epitope within any one of SEQ ID NOs: 2, 4, 6, 8, 10, or 12. ### Claim 12 (depends on 1) A method of treating or reducing the risk of a ZIKV infection in a subject in need thereof and/or reducing a ZIKV-mediated activity in a subject infected with a ZIKV, wherein said ZIKV-mediated activity is viral titer, viral spread, infection, or cell fusion, the method comprising administering to the subject a therapeutically effective amount of at least one of the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a composition comprising the nucleic acid molecule, polypeptide or vector, an immunogenic composition comprising the composition, an antibody specifically binding to the polypeptide, and/or a neutralizing anti-ZIKV antisera produced by administering to a subject the nucleic acid molecule, polypeptide, vector, composition, or immunogenic composition. ### Claim 13 (depends on 12) The method of claim 12, wherein: (i) the therapeutically effective amount of the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera is sufficient to produce a log serum anti-Env antibody titer greater than 2 in the subject, as measured by an ELISA assay; (ii) the therapeutically effective amount is between 15 μg and 300 μg of the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera; (iii) the ZIKV titer is decreased after administration of the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera; and/or (iv) the ZIKV is undetectable after administration of the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera. ### Claim 14 (depends on 12) The method of claim 12, wherein said administering occurs: (i) prior to exposure to a ZIKV; (ii) at least 1 hour prior to exposure to said ZIKV; (iii) post-exposure to the ZIKV; or (iv) at least 15 minutes post-exposure to said ZIKV. ### Claim 15 (depends on 12) The method of claim 12, wherein: (i) the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera is administered to said subject in at least one dose, in at least two doses, as a prime, as a boost, or as a prime-boost; and/or (ii) the nucleic acid molecule, the polypeptide, the vector, the composition, the immunogenic composition, the antibody, and/or the neutralizing anti-ZIKV antisera is administered to said subject intramuscularly, intravenously, intradermally, percutaneously, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctivelly, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, by catheter, by lavage, by gavage, in creams, or in lipid compositions. ### Claim 16 (depends on 12) The method of claim 12, wherein: (i) the subject is a mammal; (ii) the subject is a human; (iii) the method promotes an immune response in said subject; and/or (iv) the method promotes a humoral immune response in said subject. ### Claim 17 (depends on 1) A method of manufacturing an immunogenic composition for treating or reducing the risk of a ZIKV infection in a subject in need thereof, said method comprising the steps of: (a) forming the immunogenic composition by admixing at least one of the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a composition comprising the nucleic acid molecule, polypeptide or vector, an antibody specifically binding to the polypeptide, and/or a neutralizing anti-ZIKV antisera produced by administering to a subject the nucleic acid molecule, the polypeptide, the vector, or the composition with a pharmaceutically acceptable carrier, excipient, or diluent; and (b) placing the immunogenic composition in a container. ### Claim 18 (depends on 1) A kit comprising: (a) a first container comprising at least one of the nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid molecule, a vector comprising the nucleic acid molecule, a composition comprising the nucleic acid molecule, polypeptide or vector, an immunogenic composition comprising the composition, an antibody specifically binding to the polypeptide, and/or a neutralizing anti-ZIKV antisera produced by administering to a subject the nucleic acid molecule, the polypeptide, the vector, the composition or the immunogenic composition; (b) instructions for use thereof; and optionally (c) a second container comprising a pharmaceutically acceptable carrier, excipient, or diluent. ### Claim 19 (depends on 18) The kit of claim 18, wherein: (i) the first container further comprises a pharmaceutically acceptable carrier, excipient, or diluent; and/or (ii) the kit optionally includes an adjuvant and/or an immunostimulatory agent. ### Claim 20 (depends on 2) A composition comprising the polypeptide of claim 2. ### Claim 21 (depends on 3) A composition comprising the vector of claim 3. ### Claim 22 (depends on 20) An immunogenic composition comprising the composition of claim 20. ### Claim 23 (depends on 21) An immunogenic composition comprising the composition of claim 21. ### Claim 24 (depends on 8) The isolated antibody or antigen-binding fragment thereof of claim 8, wherein the isolated antibody or antigen-binding fragment thereof is an isolated humanized antibody or an antigen-binding fragment thereof, an isolated IgG antibody or an antigen-binding fragment thereof, or a bis-Fab, Fv, Fab, Fab′-SH, F(ab′)2, a diabody, a linear antibody, or a scFV. ### Claim 25 (depends on 12) The method of claim 12, wherein: (i) the ZIKV is a ZIKV strain from an Asian or African lineage; or (ii) the ZIKV is a ZIKV strain from Brazil or Puerto Rico, wherein optionally the ZIKV is Brazil-ZKV2015 or PRVABC59. ### Claim 26 (depends on 12) The method of claim 12, wherein the antibody is an isolated humanized antibody or an antigen-binding fragment thereof, an isolated IgG antibody or an antigen-binding fragment thereof, or a bis-Fab, Fv, Fab, Fab′-SH, F(ab′)2, a diabody, a linear antibody, or a scFV. ### Claim 27 (depends on 17) The method of claim 17, wherein the antibody is an isolated humanized antibody or an antigen-binding fragment thereof, an isolated IgG antibody or an antigen-binding fragment thereof, or a bis-Fab, Fv, Fab, Fab′-SH, F(ab′)2, a diabody, a linear antibody, or a scFV. ### Claim 28 (depends on 18) The kit of claim 18, wherein the antibody is an isolated humanized antibody or an antigen-binding fragment thereof, an isolated IgG antibody or an antigen-binding fragment thereof, or a bis-Fab, Fv, Fab, Fab′-SH, F(ab′)2, a diabody, a linear antibody, or a scFV.