Stabilized human immunodeficiency virus (HIV) clade C envelope (Env) trimer vaccines and methods of using same

Patent metadata

Field	Value
Publication number	US-10716845-B2
Application number	US-201415026391-A
Country	US
Kind code	B2
Filing date	Oct 3, 2014
Priority date	Oct 4, 2013
Publication date	Jul 21, 2020
Grant date	Jul 21, 2020

Abstract

The invention features stabilized human immunodeficiency virus (H IV) clade C envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV clade C Env trimers. In addition, the invention features methods of making and using the stabilized HIV clade C Env trimers of the invention.

First claim

The invention claimed is:

1. An immunogenic composition comprising a gp140 polypeptide, wherein the polypeptide comprises:
(a) at least 90% sequence identity over the entire length of SEQ ID NO: 1 and has a V1/V2 epitope corresponding to amino acids 166-183 of SEQ ID NO: 1 and a V3 epitope corresponding to amino acids 342-348 of SEQ ID NO: 1;
(b) at least 90% sequence identity over the entire length of SEQ ID NO: 2 and has a V1/V2 epitope corresponding to amino acids 155-172 of SEQ ID NO: 2 and a V3 epitope corresponding to amino acids 330-335 of SEQ ID NO: 2; or
(c) at least 90% sequence identity over the entire length of SEQ ID NO: 3 and has a V1/V2 epitope corresponding to amino acids 150-167 of SEQ ID NO: 3 and a V3 epitope corresponding to amino acids 328-334 of SEQ ID NO: 3;

wherein the polypeptide is capable of inducing a neutralizing antibody response.

2. The immunogenic composition of claim 1 comprising a stabilized trimer of the gp140 polypeptide, wherein each of the gp140 polypeptides of the stabilized trimer has the same amino acid sequence.

3. The immunogenic composition of claim 2 comprising at least two different stabilized trimers.

4. The immunogenic composition of claim 2 , wherein the amino acid sequence of each of the gp140 polypeptides of the stabilized trimer has at least 95% sequence identity over the entire length of any one of SEQ ID NOs: 1, 2, and 3.

5. The immunogenic composition of claim 2 , wherein said composition further comprises a stabilized C97ZA012 gp140 trimer.

6. The immunogenic composition of claim 1 , further comprising: (i) a pharmaceutically acceptable carrier, excipient, or diluent, and/or (ii) an adjuvant.

7. A kit comprising:
(a) the immunogenic composition of claim 1 ;
(b) a pharmaceutically acceptable carrier, excipient, or diluent; and
(c) instructions for use thereof, wherein said kit optionally includes an adjuvant.

8. The immunogenic composition of claim 1 , wherein the amino acid sequence of the gp140 polypeptide has at least 95% sequence identity over the entire length of SEQ ID NO: 1, 2, or 3.

9. The immunogenic composition of claim 8 , wherein the amino acid sequence of the gp140 polypeptide comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3.

10. The immunogenic composition of claim 4 , wherein the amino acid sequence of each of the gp140 polypeptides of the stabilized trimer has at least 99% sequence identity-over the entire length of any one of SEQ ID NOs: 1, 2, and 3.

11. The immunogenic composition of claim 10 , wherein each of the gp140 polypeptides of the stabilized trimer comprises the amino acid sequence of any one of SEQ ID NOs: 1, 2, and 3.

12. The immunogenic composition of claim 8 , wherein the amino acid sequence of the gp140 polypeptide has at least 99% sequence identity over the entire length of SEQ ID NO: 1, 2, or 3.

13. The immunogenic composition of claim 1 , wherein the polypeptide of (a) further comprises one or more of amino acids 121-128, 287-295, 375-386, 434-441, 462-468, or 478-486 of SEQ ID NO: 1.

14. The immunogenic composition of claim 1 , wherein the polypeptide of (b) further comprises one or more of amino acids 121-128, 275-283, 361-372, 408-415, 436-442, or 455-463 of SEQ ID NO: 2.

15. The immunogenic composition of claim 1 , wherein the polypeptide of (c) further comprises one or more of amino acids 121-128, 273-281, 361-372, 419-426, 447-453, or 466-474 of SEQ ID NO: 3.

16. The immunogenic composition of claim 1 , wherein the polypeptide of (a) further comprises amino acids 121-128, 287-295, 375-386, 434-441, 462-468, and 478-486 of SEQ ID NO: 1.

17. The immunogenic composition of claim 1 , wherein the polypeptide of (b) further comprises amino acids 121-128, 275-283, 361-372, 408-415, 436-442, and 455-463 of SEQ ID NO: 2.

18. The immunogenic composition of claim 1 , wherein the polypeptide of (c) further comprises amino acids 121-128, 273-281, 361-372, 419-426, 447-453, and 466-474 of SEQ ID NO: 3.

Assignees

• Beth Israel Deaconess Medical Ct Inc

Inventors

• Barouch Dan H
• Bricault Christine

Classifications

• A61K39/12 Primary

  Viral antigens · CPC title

• C12N2740/15034

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

• A61K2039/575

  humoral response · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K2039/55566

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