Biochemically stabilized HIV-1 Env trimer vaccine

Patent metadata

Field	Value
Publication number	US-11229696-B2
Application number	US-202016858808-A
Country	US
Kind code	B2
Filing date	Apr 27, 2020
Priority date	Oct 10, 2008
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

Stabilized trimers of a clade A strain and a clade C strain of HIV-1 are provided. Broadly neutralizing antisera against HIV-1, methods of making broadly neutralizing antisera against HIV-1, broadly neutralizing vaccines against HIV-1, as well as methods of treating subjects infected with HIV, preventing HIV infection, and inhibiting HIV-mediated activities are also provided.

First claim

What is claimed:

1. A method of inducing an immune response against HIV in a subject, the method comprising:
a. administering to the subject a first immunogenic composition comprising an immunologically effective amount of a gp140 polypeptide trimer, wherein the trimer comprises three identical polypeptide sequences, each polypeptide sequence comprising an amino acid sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2; and
b. subsequently administering to the subject a second immunogenic composition comprising an immunologically effective amount of a gp140 polypeptide trimer, wherein the trimer comprises three identical polypeptide sequences, each polypeptide sequence comprising an amino acid sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2;

wherein the first and/or second immunogenic composition further comprise an adjuvant.

2. A method of inducing an immune response against HIV in a subject, the method comprising:
a. administering to the subject a first immunogenic composition comprising a nucleic acid sequence encoding one or more HIV-1 envelope polypeptide(s); and
b. subsequently administering to the subject a second immunogenic composition comprising an immunologically effective amount of a gp140 polypeptide trimer, wherein the trimer comprises three identical polypeptide sequences, each polypeptide sequence comprising an amino acid sequence that is at least 98% identical to residues 30-708 of SEQ ID NO:2.

3. The method of claim 1 , wherein the gp140 polypeptide sequence of the first and/or second immunogenic composition includes an oligomerization domain.

4. The method of claim 3 , wherein the oligomerization domain is a T4 fibritin trimerization domain.

5. The method of claim 1 , wherein the gp140 polypeptide sequence of the first and/or second immunogenic composition includes SEQ ID NO:6 and/or SEQ ID NO:8.

6. The method of claim 2 , wherein the nucleic acid sequence encoding one or more HIV-1 envelope polypeptide(s) is comprised in a vector.

7. The method of claim 6 , wherein the vector is an expression vector.

8. The method of claim 1 , wherein the subject is infected with HIV-1.

9. The method of claim 8 , wherein administration of the first and second immunogenic compositions treats or inhibits an HIV-1 mediated activity in the subject.

10. The method of claim 8 , wherein administration of the first and second immunogenic compositions inhibits or prevents the spread of HIV in the subject.

11. The method of claim 1 , wherein the subject is not infected with HIV.

12. The method of claim 11 , wherein administration of the first and second immunogenic compositions inhibits or prevents infection by HIV of the subject.

13. The method of claim 2 , wherein the subject is infected with HIV.

14. The method of claim 13 , wherein administration of the first and second immunogenic compositions inhibits or prevents the spread of HIV in the subject.

15. The method of claim 2 , wherein the subject is not infected with HIV.

16. The method of claim 15 , wherein administration of the first and second immunogenic compositions inhibits or prevents infection by HIV of the subject.

17. The method of claim 2 , wherein the second immunogenic composition further comprises an adjuvant.

18. The method of claim 1 , wherein the method induces cellular and/or humoral immune responses.

19. The method of claim 2 , wherein the method induces cellular and/or humoral immune responses.

Assignees

• Beth Israel Deaconess Medical Ct Inc
• Childrens Medical Center

Inventors

• Harrison Stephen C
• Chen Bing
• Barouch Dan
• Nkolola Joseph P
• Seaman Michael Scott

Classifications

• A61K39/21 Primary

  Retroviridae, e.g. equine infectious anemia virus · CPC title

• A61P31/18

  for HIV · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/55566

  Emulsions, e.g. Freund's adjuvant, MF59 · CPC title