JPWO2020117590A5 - - Google Patents

Claims (25)

An isolated polypeptide having a peptide sequence that is at least 75% identical to a sequence selected from the group consisting of SEQ ID NO: 2, 4, 6, 8, 11 and 13, wherein said polypeptide comprises SEQ ID NO: 1 A polypeptide comprising substitutions at positions corresponding to N133, N137 and N156. 2. The polypeptide of claim 1, wherein said polypeptide comprises an N156Q substitution or a N156 conservative substitution. 2. The polypeptide of claim 1, wherein said polypeptide further comprises V134Y, T135A, I138L, T139L, D140S, D141N, T320F, Q328M, T415V substitutions or conservative substitutions thereof. 4. The polypeptide of any one of claims 1-3, which binds a broadly neutralizing antibody with an affinity having a K _D of about 50 μM or less. 5. The polypeptide of claim 4, wherein said broadly neutralizing antibody is the 10-1074 or PGT121 broadly neutralizing antibody. A nucleic acid molecule encoding a polypeptide according to any one of claims 1-5. A vector comprising the nucleic acid molecule of claim 6 . A host cell comprising the nucleic acid of claim 6 . A protein complex comprising at least one polypeptide according to any one of claims 1-5. A virus-like particle comprising at least one polypeptide according to any one of claims 1-5. An immunogenic composition for stimulating an immune response in a subject in need thereof, comprising: (i) a polypeptide according to any one of claims 1 to 5; claim 6; the host cell of claim 8, the protein complex of claim 9 or the virus particle of claim 10, and (ii) a pharmaceutically acceptable carrier. . A pharmaceutical composition for use in a method of stimulating an immune response in a subject in need thereof, said method comprising a polypeptide according to any one of claims 1 to 5, claim 7. administering to said subject an effective amount of a composition comprising the nucleic acid of claim 6, the host cell of claim 8, the protein complex of claim 9 or the viral particle of claim 10, or a combination thereof A pharmaceutical composition , comprising administering. 13. The pharmaceutical composition of claim 12 , wherein in said method said composition is administered to said subject more than once. 13. The pharmaceutical composition of claim 12, wherein in said method, administration of said composition increases the number of broadly neutralizing antibodies in serum capable of recognizing V3-glycan epitopes. A pharmaceutical composition for use in a method of treating or preventing HIV infection in a subject in need thereof, said method according to any one of claims 1-5. The nucleic acid of claim 6, the host cell of claim 8, the protein complex of claim 9, or the virus particle of claim 10, or a combination thereof. A pharmaceutical composition , comprising administering to a subject. A polypeptide according to any one of claims 1 to 5, a nucleic acid according to claim 6, a host cell according to claim 8, in the preparation of a medicament for the treatment or prevention of HIV infection in a subject. , a protein complex according to claim 9 or a virus particle according to claim 10, or a combination thereof. culturing the host cell according to claim 8 in a medium under conditions that allow expression of the polypeptide encoded by the nucleic acid, and purifying the polypeptide from the cultured cells or the medium of the cells. A method of producing a polypeptide, comprising: 16. The pharmaceutical composition of claim 15, wherein said method further comprises administering to said subject a therapeutically effective amount of an antiviral agent. (i) a polypeptide according to any one of claims 1 to 5, a nucleic acid according to claim 6, a host cell according to claim 8, a protein complex according to claim 9 or according to claim 10; (ii) instructions for administering said polypeptide, said nucleic acid, said host cell, said protein complex or said viral particle; and (iii) optionally A kit containing an adjuvant. A method of detecting or isolating HIV-1 binding antibodies in a subject infected with HIV-1, comprising:
The polypeptide according to any one of claims 1 to 5, the nucleic acid according to claim 6, the host cell according to claim 8, the protein complex according to claim 9 or the virus according to claim 10. providing particles, or a combination thereof ;
contacting an immunogenic composition with an amount of bodily fluid from said subject;
detecting binding of said HIV-1 binding antibody to said polypeptide thereby detecting or isolating said HIV-1 binding antibody in a subject. An isolated anti-HIV antibody, or antigen-binding portion thereof, comprising complementarity determining regions having a sequence that is at least 75% identical to a polypeptide sequence listed in Tables 4, 5, 6, 7, 9, 10 and 11. 22. A pharmaceutical composition comprising the isolated anti-HIV antibody or antigen-binding portion thereof of claim 21 and a pharmaceutically acceptable carrier or excipient. A pharmaceutical composition for use in a method of preventing or treating HIV infection or HIV-related disease, said method comprising
identifying patients in need of such prophylaxis or treatment;
administering to said patient a first therapeutic agent comprising a therapeutically effective amount of at least one anti-HIV antibody or antigen-binding portion thereof according to claim 21. 24. The pharmaceutical composition of claim 23, wherein said method further comprises administering a second therapeutic agent. 22. A kit comprising a pharmaceutically acceptable dosage unit of at least one isolated anti-HIV antibody or antigen-binding portion thereof of claim 21 in a pharmaceutically effective amount.