Antiviral vaccines with improved cellular immunogenicity

• US 10,426,831 B2
• Filed: 04/17/2017
• Issued: 10/01/2019
• Est. Priority Date: 11/18/2008
• Status: Expired due to Fees

• Current Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.), BETH Israel Deaconess Medical Center (Caregroup Incorporated), TRIAD National Security, LLC
• Original Assignee: Beth Israel Deaconess Medical Center, Inc. (Beth Israel Lahey Health, Inc.)
• Inventors: Barouch, Dan H., Korber, Bette T., Fischer, William M.
• Primary Examiner(s): Andres, Janet L
• Assistant Examiner(s): Snyder, Stuart W
• Application Number:
  US15/489,220
• Publication Number:
  US 20170239344A1
• Time in Patent Office: 897 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/235 Adenoviridae
• CPC Class Codes: A61K 39/275 Poxviridae, e.g. avipoxvirus
• CPC Class Codes: A61P 31/12 Antivirals
• 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: C12N 2710/10043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/24043 viral genome or elements thereof as genetic vector
• 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 2740/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• 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 2740/16271 Demonstrated in vivo effect
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16334 : 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
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compositions, methods, and kits for the treatment or prevention of viral infections. The polyvalent (e.g., 2-valent) vaccines described herein incorporate computationally-optimized viral polypeptides that can increase the diversity or breadth and depth of cellular immune response in vaccinated subjects.

Claims

1. A nucleic acid molecule encoding a polypeptide comprising a sequence at least 99% identical to SEQ ID NO:

3.

2. The nucleic acid molecule of claim 1, wherein the nucleic acid molecule encodes a polypeptide comprising the sequence of SEQ ID NO:

3.

3. The nucleic acid molecule of claim 1, wherein the nucleic acid molecule further comprises a nucleic acid molecule encoding a polypeptide comprising a sequence at least 99% identical to SEQ ID NO:

12.

4. The nucleic acid molecule of claim 3, wherein the nucleic acid molecule encodes a polypeptide comprising a sequence at least 99% identical to SEQ ID NO:

21.

5. The nucleic acid molecule of claim 4, wherein the nucleic acid molecule encodes a polypeptide comprising the sequence of SEQ ID NO:

21.

6. A vector comprising the nucleic acid molecule of claim 1.

7. A vector comprising the nucleic acid molecule of claim 2.

8. A vector comprising the nucleic acid molecule of claim 5.

9. The vector of claim 6, wherein said vector is an adenoviral vector or a pox virus vector.

10. The vector of claim 7, wherein said vector is an adenoviral vector or a pox virus vector.

11. The vector of claim 8, wherein said vector is an adenoviral vector or a pox virus vector.

12. The vector of claim 9, wherein said vector is selected from the group consisting of adenovirus serotype 26 (Ad26), adenovirus serotype 34 (Ad34), adenovirus serotype 35 (Ad35), adenovirus serotype 48 (Ad48), and adenovirus serotype 5 HVR48 (Ad5HVR48).

13. The vector of claim 9, wherein said vector is Ad26.

14. The vector of claim 10, wherein said vector is Ad26.

15. The vector of claim 11, wherein said vector is Ad26.

16. The vector of claim 9, wherein said vector is a modified vaccinia virus Ankara (MVA).

17. The vector of claim 10, wherein said vector is MVA.

18. The vector of claim 11, wherein said vector is MVA.

19. A pharmaceutical composition comprising the vector of claim 6 and a pharmaceutically acceptable carrier, excipient, or diluent.

20. A pharmaceutical composition comprising the vector of claim 7 and a pharmaceutically acceptable carrier, excipient, or diluent.

21. A pharmaceutical composition comprising the vector of claim 8 and a pharmaceutically acceptable carrier, excipient, or diluent.

22. The pharmaceutical composition of claim 19, wherein said vector is an adenoviral vector or a pox virus vector.

23. The pharmaceutical composition of claim 20, wherein said vector is an adenoviral vector or a pox virus vector.

24. The pharmaceutical composition of claim 21, wherein said vector is an adenoviral vector or a pox virus vector.

25. The pharmaceutical composition of claim 22, wherein said vector is selected from the group consisting of Ad26, Ad34, Ad35, Ad48, Ad5HVR48, and MVA.

26. The pharmaceutical composition of claim 22, wherein said vector is Ad26.

27. The pharmaceutical composition of claim 23, wherein said vector is Ad26.

28. The pharmaceutical composition of claim 24, wherein said vector is Ad26.

29. The pharmaceutical composition of claim 22, wherein said vector is MVA.

30. The pharmaceutical composition of claim 23, wherein said vector is MVA.

31. The pharmaceutical composition of claim 24, wherein said vector is MVA.

32. A kit comprising:

a) the pharmaceutical composition of claim 19;

b) instructions for use thereof; and

, optionally,

c) an adjuvant.

33. A method for inducing an HIV-1 specific immune response in a mammal comprising administering to said mammal the nucleic acid of claim 1 or a vector comprising said nucleic acid.

34. A method for inducing an HIV-1 specific immune response in a mammal comprising administering to said mammal the nucleic acid of claim 2 or a vector comprising said nucleic acid.

35. A method for inducing an HIV-1 specific immune response in a mammal comprising administering to said mammal the nucleic acid of claim 5 or a vector comprising said nucleic acid.

36. The method of claim 33, wherein said nucleic acid or said vector is in a pharmaceutical composition.

37. The method of claim 33, wherein said vector is Ad26.

38. The method of claim 33, wherein said vector is MVA.

39. The method of claim 33, wherein said mammal is a human.

40. A method of manufacturing the pharmaceutical composition of claim 19, said method comprising combining a vector comprising a nucleic acid molecule encoding a polypeptide comprising a sequence at least 99% identical to SEQ ID NO:

3 with a pharmaceutically acceptable carrier, excipient, or diluent.