Biochemically stabilized HIV-1 Env trimer vaccine

Patent metadata

Field	Value
Publication number	US-10653770-B2
Application number	US-201916579025-A
Country	US
Kind code	B2
Filing date	Sep 23, 2019
Priority date	Oct 10, 2008
Publication date	May 19, 2020
Grant date	May 19, 2020

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. An isolated nucleic acid molecule encoding at least one gp140 polypeptide, wherein said gp140 polypeptide comprises an amino acid sequence at least 98% identical to residues 1-708 of SEQ ID NO:2.

2. The isolated nucleic acid molecule of claim 1 , wherein the gp140 polypeptide comprises an oligomerization domain.

3. The isolated nucleic acid molecule of claim 2 , wherein said oligomerization domain is a T4 fibritin trimerization domain.

4. The isolated nucleic acid molecule of claim 1 , wherein said amino acid sequence includes SEQ ID NO:8 and/or SEQ ID NO:6.

5. A vector comprising the isolated nucleic acid molecule of claim 1 .

6. The vector of claim 5 , wherein said vector is a plasmid.

7. The vector of claim 5 , further comprising a promoter that drives expression of said gp140 polypeptide.

8. A method of recombinantly producing a gp140 polypeptide, said method comprising the steps of:
(a) contacting a cell with the vector of claim 5 ;
(b) expressing said at least one gp140 polypeptide; and
(c) purifying said gp140 polypeptide.

9. The method of claim 8 , wherein the expressed gp140 polypeptides form a stabilized trimer.

10. The method of claim 8 , wherein said cell is a bacterial cell, a yeast cell, an insect cell, or a mammalian cell.

11. The method of claim 10 , wherein said cell is a mammalian cell.

12. A pharmaceutical composition comprising the recombinantly produced gp140 polypeptide of claim 9 and a pharmaceutically acceptable carrier, excipient, or diluent.

13. The pharmaceutical composition of claim 12 , further comprising an adjuvant.

14. A method of treating or inhibiting an HIV-1 mediated activity in a subject infected with HIV-1 comprising contacting a subject infected with HIV-1 with the pharmaceutical composition of claim 12 , thereby inducing production of anti-HIV-1 antibodies in the subject, wherein the anti-HIV-1 antibodies treat or inhibit the HIV-1 mediated activity in the subject infected with HIV-1.

15. The method of claim 14 , wherein the anti-HIV-1 antibodies are selected from one or more of anti-HIV-1 clade A antibodies, anti-HIV-1 clade B antibodies, and anti-HIV-1 clade C antibodies.

16. The method of claim 14 , wherein the HIV-1 titer in the subject infected with HIV-1 is decreased after contacting the subject with the pharmaceutical composition.

17. The method of claim 14 , wherein the HIV-1 mediated activity is viral spread.

18. A method of inducing an immune response against HIV-1 in a subject, the method comprising:
a. contacting a subject with the pharmaceutical composition of claim 12 ; and
b. inducing an immune response against HIV-1 in the subject.

19. The method of claim 18 , wherein the subject is not infected with HIV-1 at the moment of administration of the pharmaceutical composition.

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

• C12N2740/16171

  Demonstrated in vivo effect · CPC title

• A61K39/21 Primary

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

• C12N2740/16122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K39/12

  Viral antigens · CPC title

• C12N2740/16134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title