Synthetic human immunodeficiency virus (HIV) envelope antigen, vectors, and compositions thereof

• US 10,369,214 B2
• Filed: 12/15/2016
• Issued: 08/06/2019
• Est. Priority Date: 12/15/2015
• Status: Active Grant

• Current Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Original Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Inventors: Langedijk, Johannes Petrus Maria, Van Manen, Danielle, Vellinga, Jort, Wegmann, Frank, Callendret, Benoit Christophe Stephan, Krarup, Anders, Stitz, Jorn
• Primary Examiner(s): Parkin, Jeffrey S
• Application Number:
  US15/380,123
• Publication Number:
  US 20170165355A1
• Time in Patent Office: 964 Days
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/162 env, e.g. gp160, gp110/120, gp41, V3, peptid T, CD4-Binding site
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 15/861 Adenoviral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2740/16111 concerning HIV env
• 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
• CPC Class Codes: C12N 2740/16171 Demonstrated in vivo effect
• CPC Class Codes: C12N 2740/16234 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

Synthetic HIV envelope proteins, vectors and compositions thereof, and methods for inducing protective immunity against human immunodeficiency virus (HIV) infection are described. Viral expression vectors encoding the synthetic HIV envelope proteins can be used in vaccines to provide improved protective immunity against HIV.

Claims

1. A nucleic acid encoding a synthetic HIV envelope protein comprising the amino acid sequence of SEQ ID NO:

8, or SEQ ID NO;

8 having one or more mutations selected from the group consisting of (i) I529P, (ii) K480E, and (iii) a combination of EK479-480RRRR, I529P, A471C and T575C.

2. The nucleic acid of claim 1, wherein the synthetic HIV envelope protein further comprises a signal sequence.

3. The nucleic acid of claim 1, wherein the synthetic HIV envelope protein further comprises a transmembrane domain.

4. The nucleic acid of claim 3, wherein the synthetic HIV envelope protein further comprises a fragment of a cytoplasmic domain.

5. The nucleic acid of claim 1, wherein the synthetic HIV envelope protein comprises the amino acid sequence of SEQ ID NO:

18.

6. The nucleic acid of claim 1, wherein the synthetic HIV envelope protein either:

(a) further comprises a trimerization domain;

or (b) comprises SEQ ID NO;

8 having a combination of mutations EK479-480RRRR, I529P, A471C and T575C.

7. The nucleic acid of claim 6, wherein the synthetic HIV envelope protein comprises the amino acid sequence of residues 1-686 of SEQ ID NO:

19.

8. A vector comprising the nucleic acid of claim 1, wherein the nucleic acid is operably linked to a promoter sequence.

9. The vector of claim 8, wherein the vector is an adenovirus vector.

10. The vector of claim 9, wherein the adenovirus vector is a human adenovirus serotype 26 (Ad26) vector.

11. An isolated cell comprising the vector of claim 8.

12. A composition comprising an immunogenically effective amount of the vector of claim 8, and a carrier.

13. The nucleic acid of claim 2, wherein the signal sequence comprises the amino acid sequence selected from the group consisting of SEQ ID NO:

9 to SEQ ID NO;

12.

14. The nucleic acid of claim 3, wherein the transmembrane domain comprises SEQ ID NO:

13.

15. The nucleic acid of claim 4, wherein the fragment of the cytoplasmic domain comprises the amino acid sequence of SEQ ID NO:

14 or residues 1-4 thereof.

16. The nucleic acid of claim 6, wherein the trimerization domain has the amino acid sequence of SEQ ID NO:

15 or SEQ ID NO;

16.

17. A vector comprising the nucleic acid of claim 5, wherein the nucleic acid is operably linked to a promoter sequence.

18. The vector of claim 17, wherein the vector is a viral vector.

19. The vector of claim 18, wherein the viral vector is an adenovirus vector.

20. The vector of claim 19, wherein the adenovirus vector is an Ad26 vector.

21. An isolated cell comprising the vector of claim 17.

22. An isolated cell comprising the vector of claim 20.

23. A composition comprising an immunogenically effective amount of the vector of claim 17, and a carrier.

24. A composition comprising an immunogenically effective amount of the vector of claim 19, and a carrier.

25. A composition comprising an immunogenically effective amount of the vector of claim 20, and a carrier.

26. The vector of claim 8, wherein the vector is a viral vector.

27. The nucleic acid of claim 14, wherein the synthetic HIV envelope protein further comprises SEQ ID NO:

37 fused to the C-terminus of SEQ ID NO;

8 and to the N-terminus of the transmembrane domain.

28. The vector of claim 18, wherein the vector is a pox virus vector.

29. The vector of claim 18, wherein the vector is an MVA (Modified Vaccinia Ankara) vector.

30. The vector of claim 26, wherein the vector is a pox virus vector.

31. The vector of claim 26, wherein the vector is an MVA (Modified Vaccinia Ankara) vector.

32. An isolated cell comprising the vector of claim 28.

33. An isolated cell comprising the vector of claim 29.

34. An isolated cell comprising the vector of claim 30.

35. An isolated cell comprising the vector of claim 31.

36. A composition comprising an immunogenically effective amount of the vector of claim 28, and a carrier.

37. A composition comprising an immunogenically effective amount of the vector of claim 29, and a carrier.

38. A composition comprising an immunogenically effective amount of the vector of claim 30, and a carrier.

39. A composition comprising an immunogenically effective amount of the vector of claim 31, and a carrier.

40. The nucleic acid of claim 5, wherein the sequence that encodes SEQ ID NO:

18 comprises the nucleic acid sequence of SEQ ID NO;

26.

41. The vector of claim 16, wherein the sequence that encodes SEQ ID NO:

18 comprises the nucleic acid sequence of SEQ ID NO;

26.

42. The vector of claim 17, wherein the sequence that encodes SEQ ID NO:

18 comprises the nucleic acid sequence of SEQ ID NO;

26.

43. An adenovirus vector comprising nucleic acid encoding a polypeptide, wherein the polypeptide comprises SEQ ID NO:

18.

44. The adenovirus vector of claim 43, wherein the adenovirus vector is an Ad26 vector.

45. The adenovirus vector of claim 43, wherein the sequence that encodes SEQ ID NO:

18 comprises the nucleic acid sequence of SEQ ID NO;

26.

46. The adenovirus vector of claim 44, wherein the sequence that encodes SEQ ID NO:

18 comprises the nucleic acid sequence of SEQ ID NO;

26.

47. A composition comprising the adenovirus vector of claim 43, and a carrier.

48. A composition comprising the adenovirus vector of claim 44, and a carrier.

49. A composition comprising the adenovirus vector of claim 45, and a carrier.

50. A composition comprising the adenovirus vector of claim 46, and a carrier.

51. The composition of claim 47, which is for intramuscular administration.