Antiviral vaccines with improved cellular immunogenicity
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.
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.