Engineered and multimerized human immunodeficiency virus envelope glycoproteins and uses thereof

• US 10,342,863 B2
• Filed: 03/24/2016
• Issued: 07/09/2019
• 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
• Primary Examiner(s): Salvoza, M Franco G
• Application Number:
  US15/561,438
• Publication Number:
  US 20180117140A1
• Time in Patent Office: 1,202 Days
• Field of Search: None
• 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

Multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins are multimerized 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 (gp 120) and can used as an HIV vaccine.

Claims

1. An engineered and multimerized (e/m) human immunodeficiency virus (HIV) envelope glycoprotein (Env) comprising:

(i) mutations, using HXB2 numbering;

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.

2. The e/m HIV Env of claim 1, wherein the N-terminal truncation is before residue 49, 48, 47, 46, 45, 44, 43, 42, 41, 40 or 39.

3. The e/m HIV Env of claim 1, wherein the N-terminal truncation is before residue 44.

4. The e/m HIV Env of claim 1, further comprising a C-terminal truncation after residue 499, 498, 497, 496, 495, 494, 493, 492, 491, 490 or 389.

5. The e/m HIV Env of claim 4, wherein the C-terminal truncation is after residue 494.

6. The e/m HIV Env of claim 1, wherein the flexible linker is selected from SEQ ID NOs:

3-13, or 126.

7. The e/m HIV Env of claim 1, wherein the V3 loop comprises 296-331.

8. The e/m HIV Env of claim 1, wherein the heptamerization domain is selected from SEQ ID NOs:

14-49 or positions 348 to 528 of SEQ ID NO;

51.

9. The e/m HIV Env of claim 1, wherein removal of the V1 loop comprises removal of 131-152 and/or removal of the V2 loop comprises removal of 161-196.

10. The e/m HIV Env of claim 1, wherein removal of the V1 loop and removal of the V2 loop comprises removal of 123-196.

11. The e/m HIV Env of claim 1, multimerized into a heptamer or a larger order multimer based on a heptamer.

12. The e/m HIV Env of claim 1, wherein the heptamerization domain comprises SEQ ID NO:

47.

13. The e/m HIV Env of claim 1, consisting of SEQ ID NO:

50.

14. The e/m HIV Env of claim 1, wherein the heptamerization domain comprises SEQ ID NO:

48.

15. The e/m HIV Env of claim 1, wherein the heptamerization domain comprises SEQ ID NO:

49.

16. The e/m HIV Env of claim 1, consisting of SEQ ID NO:

51.

17. The e/m HIV Env of claim 1, consisting of SEQ ID NO:

52.