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1. WO2020117590 - HIV VACCINE IMMUNOGENS

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[ EN ]

CLAIMS

We claim:

1. An isolated polypeptide having a peptide sequence that is at least 75% identical to a sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, 11, and 13, wherein the polypeptide comprises substitutions at the positions corresponding to N133, N137, and N156 of SEQ ID NO: 1.

2. The polypeptide of Claim 1, wherein the polypeptide comprises an N156Q substitution or a conservative substitution of N156.

3. The polypeptide of Claim 1 , wherein the polypeptide further comprises V134Y, T135A, I138L, T139L, D140S, D141N, T320F, Q328M, T415V substituions or conservative substitutions thereof.

4. The polypeptide of any one of the preceding claims binds to a broadly neutralizing antibody with an affinity having a KD of about 50 mM or less.

5. The polypeptide of Claim 4, wherein the broadly neutralizing antibody is 10-1074 or PGT121 broadly neutralizing antibody.

6. A nucleic acid molecule encoding the polypeptide of any one of the preceding claims.

7. A vector comprising the nucleic acid molecule of Claim 6.

8. A host cell comprising the nucleic acid of Claim 6.

9. A protein complex comprising at least one polypeptide of any one of Claims 1-5. 10. A virus-like particle comprising at least one polypeptide of any one of Claims 1-5.

11. An immunogenic composition for stimulating an immune response in a subject in need thereof, comprising (i) the polypeptide of 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; and (ii) a pharmaceutically acceptable carrier.

12. A method of stimulating an immune response in a subject in need thereof, comprising administrating to the subject an effective amount of a composition comprising the polypeptide of 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.

13. The method of Claim 12, wherein the composition is administered to the subject two or more times.

14. The method of Claim 12, wherein administrating the composition results in increased numbers of broadly-neutralizing antibodies in the serum capable of recognizing a V3-glycan epitope.

15. A method of treating or preventing HIV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the polypeptide of 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.

16. Use of the polypeptide of 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 in the preparation of a medicament to treat or prevent HIV infection in a subject.

17. A method of producing a polypeptide, comprising culturing the host cell of Claim 8 in a medium under conditions permitting expression of a polypeptide encoded by the nucleic acid, and purifying the polypeptide from the cultured cell or the medium of the cell.

18. The method of Claim 15, further comprising administering to the subject a therapeutically effective amount of an anti- viral agent.

19. A kit, comprising (i) one or more unit dosages of the polypeptide of 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; (ii) instructions for administrating the polypeptide, the nucleic acid, the host cell, the protein complex, or the virus particle; and (iii) optionally an adjuvant.

20. A method for detecting or isolating an HIV-1 binding antibody in a subject infected with HIV-1, comprising:

providing the polypeptide of 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;

contacting the immunogenic composition with an amount of bodily fluid from the subject; and

detecting binding of the HIV- 1 binding antibody to the polypeptide, thereby detecting or isolating the HIV-1 binding antibody in a subject.

21. An isolated anti- HIV antibody, or antigen-binding portion thereof, comprising a complementarity-determining region 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.

23. A method of preventing or treating an HIV infection or an HIV-related disease comprising the steps of :

identifying a patient in need of such prevention or treatment, and

administering to said patient a first therapeutic agent comprising a therapeutically effective amount of at least one anti- HIV antibody of Claim 21, or antigen-binding portion thereof.

24. The method of claim 23, further comprising administering a second therapeutic agent.

25. A kit comprising a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of at least one isolated anti- HIV antibody of Claim 21, or antigen-binding portion thereof.