Nucleic acids encoding human immunodeficiency virus type 1 (HIV-1) N-terminal deleted gp120 immunogens and methods of use

Patent metadata

Field	Value
Publication number	US-11053285-B2
Application number	US-201816020543-A
Country	US
Kind code	B2
Filing date	Jun 27, 2018
Priority date	Jul 5, 2011
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

The present invention relates, in general, to human immunodeficiency virus (HIV), and in particular to a vaccine for HIV-1 and to methods of making and using same.

First claim

What is claimed is:

1. A nucleic acid encoding a recombinant protein comprising an HIV-1 envelope (Env) gp120 or gp140, wherein the original 4 to 25 consecutive amino acids of the N-terminus are deleted, wherein the deleted consecutive amino acids are located immediately after the envelope signal peptide and wherein an N-terminal Herpes Simplex gD tag is not substituted for amino acids of the N-terminus.

2. The nucleic acid according to claim 1 , wherein 5 to 11 consecutive amino acids of the N-terminus of the recombinant protein are deleted.

3. The nucleic acid according to claim 1 , wherein eleven (11) consecutive amino acids of the N-terminus of the recombinant protein are deleted.

4. The nucleic acid according to claim 1 , wherein seven (7) consecutive amino acids of the N-terminus of the recombinant protein are deleted.

5. The nucleic acid according to claim 1 , wherein said HIV-1 Env is gp120.

6. The nucleic acid according to claim 5 , wherein said HIV-1 Env is A244, 1086.C, 089.C, 63521.B, CONS or 6240.B.

7. The nucleic acid according to claim 5 , wherein said HIV-1 Env is 040.B or A1C recombinant Env 707-01-069-2.

8. The nucleic acid according to claim 3 , wherein the HIV-1 Env is 63521.B delta 11, A244 delta 11, 6240.B delta 11, MCON-S delta 11, or 089.0 delta 11.

9. The nucleic acid according to claim 4 , wherein the HIV-1 Env is 1086.0 delta 7.

10. The nucleic acid according to claim 5 , wherein said HIV-1 Env comprises the consecutive amino acids immediately after the signal peptide in SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

11. A composition comprising said nucleic acid according to claim 1 and a carrier.

12. A composition comprising a nucleic acid encoding a recombinant protein comprising an HIV-1 Env gp120 and an adjuvant, wherein the original 4 to 25 consecutive amino acids of the N-terminus of the HIV-1 Env gp120 are deleted, wherein the deleted consecutive amino acids are located immediately after the envelope signal peptide and wherein an N-terminal Herpes Simplex gD tag is not substituted for amino acids of the N-terminus of gp120.

13. The composition of claim 12 , wherein 5 to 11 consecutive amino acids of the N-terminus of the HIV-1 Env gp120 are deleted.

14. The composition of claim 13 , wherein seven (7) or eleven (11) consecutive amino acids of the N-terminus of the HIV-1 Env gp120 are deleted.

15. The composition of claim 12 , wherein the recombinant HIV-1 protein comprises the consecutive amino acids immediately after the signal peptide in SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

16. A method of inducing an immune response in a subject comprising administering to the subject the composition of claim 12 in an amount sufficient to induce the immune response.

17. The method of claim 16 , wherein 5 to 11 consecutive amino acids of the N-terminus of the recombinant HIV-1 Env gp120 encoded by the nucleic acid comprised in the composition are deleted.

18. The method of claim 16 , wherein seven (7) or eleven (11) consecutive amino acids of the N-terminus of the recombinant HIV-1 Env gp120 encoded by the nucleic acid comprised in the composition are deleted.

19. The method of claim 16 , wherein the recombinant HIV-1 Env gp120 encoded by the nucleic acid comprised in the composition protein comprises the consecutive amino acids immediately after the signal peptide in SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

20. A method of inducing an immune response in a subject comprising administering to said subject said nucleic acid according to claim 1 in an amount and manner sufficient to induce the immune response.

21. The method of claim 20 , wherein 5 to 11 consecutive amino acids of the N-terminus of the recombinant HIV-1 Env encoded by the nucleic acid are deleted.

22. The method of claim 20 , wherein seven (7) or eleven (11) consecutive amino acids of the N-terminus of the recombinant HIV-1 Env encoded by the nucleic acid are deleted.

23. The method of claim 20 , wherein the recombinant HIV-1 Env comprises the consecutive amino acids immediately after the signal peptide in SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 10, or SEQ ID NO: 12.

24. A vector comprising the nucleic acid according to claim 1 .

25. The vector according to claim 24 wherein said vector is a rAdenovirus, recombinant mycobacteria or recombinant vaccinia type vector.

Assignees

• Univ Duke
• Us Gov Sec Army
• Childrens Medical Center

Inventors

• Kim Jerome
• Harrison Stephen
• Haynes Barton F
• Tomaras Georgia D
• Michael Nelson

Classifications

• C07K16/1145

  Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site · CPC title

• C07K14/162

  env, e.g. gp160, gp110/120, gp41, V3, peptid T, CD4-Binding site · CPC title

• A61K39/12

  Viral antigens · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C12N2740/16134

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