ENGINEERED AND MULTIMERIZED HUMAN IMMUNODEFICIENCY VIRUS ENVELOPE GLYCOPROTEINS AND USES THEREOF

• US 20190321461A1
• Filed: 06/03/2019
• Published: 10/24/2019
• Est. Priority Date: 03/24/2015
• Status: Active Grant

• Current Assignee: Fred Hutchinson Cancer Center
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Strong, Roland K., Correnti, Colin, Stamatatos, Leonidas, McGuire, Andrew
• Granted Patent: US 10,987,417 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/16 HIV-1 ; HIV-2
• CPC Class Codes: C12N 2740/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Engineered and multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins can be multimerized using a heptamerization domain such as a C4b binding protein multimerization domain or a ferritin fusion. The engineered and multimerized envelope glycoproteins can derived from glycoprotein 120 (gp120) and can used as an HIV vaccine.

Claims

1. An engineered and multimerized (e/m) human immunodeficiency virus (HIV) envelope glycoprotein (Env) comprising SEQ ID NO:

50.

8. An e/m Env of any one of claims 1-7, multimerized into a heptamer or a larger order multimer based on a heptamer.

9. A composition comprising a fusion protein of claim 8.

10. A kit comprising an e/m Env of claim 8.

11. A vector encoding an e/m Env of claim 8.

12. A host cell comprising a vector of claim 11.

2. An e/m Env comprising an artificial human immunodeficiency virus (HIV) envelope glycoprotein selected from SEQ ID NOs:

52-121 and a heptamerization domain selected from SEQ ID NOs;

14-49 or 51.

3. An e/m Env comprising an artificial HIV envelope glycoprotein selected from SEQ ID NO:

52 and a heptamerization domain selected from SEQ ID NO;

14 or SEQ ID NOs;

14-49 or 51.

4. An e/m Env comprising an HIV envelope glycoprotein and a heptamerization domain.

5. An e/m Env of claim 4, wherein the heptamerization domain is selected from SEQ ID NOs:

14-49 or 51.

6. An e/m Env of claim 4, wherein the HIV envelope glycoprotein is an artificial gp120.

7. An e/m Env of claim 6, wherein the artificial gp120 is selected from SEQ ID NOs:

52-121.

13. An e/m Env comprising:

(i) mutations;

N460D;

N463D;

S278R;

G471S;

V65C; and

S115C;

(ii) removal of the V1 loop and the V2 loop;

(iii) replacement of the V3 loop with a flexible linker;

(iv) an N-terminal truncation; and

(v) a heptamerization domain;

wherein the e/m Env does not include a mutation at position 276.

14. An e/m Env of claim 13 wherein the N-terminal truncation is before residue 49, 48, 47, 46, 45, 44, 43, 42, 41, 40 or 39.

15. An e/m Env of claim 13 wherein the N-terminal truncation is before residue 44.

16. An e/m Env of claim 13 further comprising a C-terminal truncation after residue 499, 498, 497, 496, 495, 494, 493, 492, 491, 490 or 389.

17. An e/m Env of claim 16 wherein the C-terminal truncation is after residue 494.

18. An e/m Env of claim 13 wherein the flexible linker is selected from SEQ ID NOs:

3-13, or 126.

19. An e/m Env of claim 13 wherein the V3 loop comprises 296-331.

20. An e/m Env of claim 13 wherein the heptamerization domain is selected from SEQ ID NOs:

14-49 or 51.

21. An e/m Env of claim 13 wherein removal of the V1 loop comprises removal of 131-152 and/or removal of the V2 loop comprises removal of 161-196.

22. An e/m Env of claim 13 wherein removal of the V1 loop and removal of the V2 loop comprises removal of 123-196.

23. An e/m Env of any one of claims 13-21, multimerized into a heptamer or a larger order multimer based on a heptamer.

24. A composition comprising a fusion protein comprising an e/m Env of claim 23.

25. A kit comprising a fusion protein of claim 24.

26. A vector encoding an e/m Env of claim 13.

27. A host cell comprising a vector of claim 26.