Compositions, methods and kits relating to poxvirus subunit vaccines

• US 20060062800A1
• Filed: 12/13/2004
• Published: 03/23/2006
• Est. Priority Date: 02/28/2003
• Status: Active Grant

• Current Assignee: Theradigm, Inc., Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Moss, Bernard, Aldaz-Carroll, Lydia, Whitbeck, John Charles, Cohen, Gary H., Fogg, Christiana, Lustig, Shlomo, Eisenberg, Roselyn J.
• Granted Patent: US 7,560,116 B2
• Time in Patent Office: Days
• US Class Current: 424/186.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/285 Vaccinia virus or variola virus
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 16/081 from DNA viruses
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 2710/24122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The invention is directed to a poxvirus vaccine comprising a soluble truncated poxvirus envelope protein. The invention is also directed to a vaccine comprising a nucleic acid encoding such proteins. Also included is an antibody which specifically binds to the proteins and nucleic acid encoding the same, as well as methods of preventing and treating a poxvirus infection using the afore-mentioned vaccine, antibody, protein, and nucleic acid encoding them.

Claims

1. A vaccine comprising a soluble truncated mammalian poxvirus envelope protein and a pharmaceutically acceptable carrier, wherein said protein is at least one protein selected from the group consisting of A33Rt, B5Rt, and L1R(185t), or a homologue thereof.

2. The vaccine of claim 1, wherein said poxvirus is at least one poxvirus selected from the group consisting of vaccinia virus and variola virus.

3. The vaccine of claim 1, said vaccine further comprising at least one protein selected from the group consisting of A17L, A27L, A34R, A56R, D8L, F9L, F13L, and H3L, or a homologue thereof.

4. The vaccine of claim 1, wherein said A33Rt comprises from about amino acid residue number 58 to 185 relative to full-length A33R (SEQ ID No:

35).

5. The vaccine of claim 4, wherein the amino acid sequence of said A33Rt is the sequence of SEQ ID NO:

3

6. The vaccine of claim 1, wherein said B5Rt comprises from about amino acid residue number 20 to 275 relative to full-length B5R (SEQ ID NO:

41).

7. The vaccine of claim 6, wherein the amino acid sequence of said B5Rt is the sequence of SEQ ID NO:

5.

8. The vaccine of claim 1, wherein said L1R(185t) comprises from about amino acid residue number 1 to 185 relative to full-length L1R (SEQ ID NO:

38).

10. The vaccine of claim 1, wherein said vaccine comprises A33Rt and L1R(185t).

11. The vaccine of claim 10, said vaccine further comprising B5Rt.

12. The vaccine of claim 3, wherein said A17L is A17Lt and comprises from about amino acid residue number 80 to 138 relative to full-length A17L.

13. The vaccine of claim 1, said vaccine further comprising at least one variola virus homologue protein selected from the group consisting of A36R, B6R, and M1R.

24. A method of immunizing a human patient against a poxvirus infection comprising administering to said patient an effective amount of the vaccine of claim 1.

25. A method of immunizing a human patient against a poxvirus infection comprising administering to said patient an effective amount of the vaccine of claim 3.

29. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the vaccine of claim 1.

9. The vaccine of claim 9, wherein the amino acid sequence of said L1R(185t) is the sequence of SEQ ID NO:

1.

14. A vaccine comprising an isolated nucleic acid encoding a soluble truncated mammalian poxvirus envelope protein and a pharmaceutically acceptable carrier, wherein said protein is at least one protein selected from the group consisting of A33Rt, B5Rt, and L1Rt(185), or a homologue thereof.

15. The vaccine of claim 14, wherein said protein is at least one vaccinia virus protein selected from the group consisting of A17L, A27L, A34R, A56R, D8L, F9L, F13L, and H3L.

16. The vaccine of claim 14, wherein the nucleotide sequence of said nucleic acid is at least one sequence selected from the group consisting of the sequence of SEQ ID NO:

1 encoding L1R(185t), sequence of SEQ ID NO;

3 encoding A33Rt, and sequence of SEQ ID NO;

5 encoding B5Rt.

27. A method of immunizing a human patient against a poxvirus infection comprising administering to said patient an effective amount of the vaccine of claim 14.

30. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the vaccine of claim 14.

17. An isolated poxvirus neutralizing antibody which specifically binds to a soluble truncated mammalian poxvirus envelope protein.

18. The antibody of claim 17, wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, and a synthetic antibody.

19. The antibody of claim 17, wherein said antibody is a monoclonal antibody that specifically binds to B5R and further wherein said antibody is selected from the group consisting of VMC-7, VMC-8, VMC-9, VMC-10, VMC-11, VMC-12, VMC-13, VMC-14, VMC-15, VMC-16, VMC-18, VMC-19, VMC-20, VMC-21, VMC-22, VMC-23, VMC-24, VMC-25, VMC-26, VMC-27, VMC-28, VMC-29, VMC-30, VMC-31, VMC-32, and VMC-33.

20. The antibody of claim 17, wherein said antibody is a monoclonal antibody that specifically binds to L1R(185t) wherein said antibody is VMC-2.

21. The antibody of claim 17, wherein said antibody is a monoclonal antibody that specifically binds to A33Rt wherein said antibody is VMC-1.

22. The isolated antibody of claim 17, wherein said protein is selected from the group consisting of A33Rt, B5Rt and L1R(185t).

23. An isolated nucleic acid encoding the antibody of claim 17.

26. A method of immunizing a human patient against a poxvirus infection comprising administering to said patient an effective amount of the nucleic acid of claim 23.

28. A method of immunizing a human patient against a poxvirus infection comprising administering to said patient an effective amount of the antibody of claim 17.

31. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the antibody of claim 17.

32. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the nucleic acid of claim 23.

33. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the antibody of claim 17 in a pharmaceutically acceptable carrier.

34. A method of treating a poxvirus infection in a human patient comprising administering to said patient an effective amount of the isolated nucleic acid of claim 23 in a pharmaceutically acceptable carrier.

53. A kit for immunizing a human patient against a poxvirus infection, said kit comprising an effective amount of the antibody of claim 17, said kit further comprising an applicator and an instructional material for the use of said kit.

56. A kit for treating a poxvirus infection in a human patient, said kit comprising an effective amount of the antibody of claim 17, said kit further comprising an applicator and an instructional material for the use of said kit.

35. A composition comprising at least one soluble truncated mammalian poxvirus envelope protein.

36. The composition of claim 35, wherein said poxvirus is at least one poxvirus selected from vaccinia virus and variola virus.

37. The composition of claim 36, wherein said protein is at least one vaccinia protein selected from the group consisting of A33Rt, B5Rt, L1R(185t), or a homologue thereof.

38. The composition of claim 37, wherein said homologue is at least one variola protein selected from the group consisting of A36R, B6R, and M1R.

39. The composition of claim 37, wherein the amino acid sequence of said A33Rt is the sequence of SEQ ID NO:

3.

40. The composition of claim 39, said composition further comprising a vaccinia L1R(185t) wherein the amino acid sequence of said L1R(185t) is the sequence of SEQ ID NO:

1.

41. The composition of claim 40, said composition further comprising a vaccinia B5Rt protein wherein the amino acid sequence of said B5Rt is the sequence of SEQ ID NO:

5.

42. The composition of claim 35, said composition further comprising a pharmaceutically acceptable carrier.

43. An isolated nucleic acid encoding a vaccinia virus soluble truncated envelope protein.

44. The isolated nucleic acid of claim 43, wherein said protein is selected from the group consisting of A33Rt, B5Rt, and L1R(185t).

45. The isolated nucleic acid of claim 44, wherein the sequence of said nucleic acid encoding A33Rt is SEQ ID NO:

4, the sequence of said nucleic acid encoding B5Rt is SEQ ID NO;

6, and further wherein the sequence of said nucleic acid encoding L1R(185t) is SEQ ID NO;

2.

46. A protein encoded by the nucleic acid of claim 43.

47. A protein encoded by the nucleic acid of claim 44.

51. A kit for immunizing a human patient against a poxvirus infection, said kit comprising an immunogenic amount of the soluble truncated poxvirus envelope protein of claim 46, said kit further comprising an applicator and an instructional material for the use of said kit.

52. A kit for immunizing a human patient against a poxvirus infection, said kit comprising an immunogenic amount of the isolated nucleic acid encoding a soluble truncated poxvirus envelope protein of claim 43, said kit further comprising an applicator and an instructional material for the use of said kit.

55. A kit for treating a poxvirus infection in a human patient, said kit comprising an immunogenic amount of the isolated nucleic acid of claim 43, said kit further comprising an applicator and an instructional material for the use of said kit.

48. An isolated mammalian poxvirus soluble truncated envelope protein.

49. The isolated protein of claim 48, wherein said poxvirus is vaccinia and further wherein said protein is selected from the group consisting of A33Rt, B5Rt, and L1R(185t).

50. The isolated protein of claim 49, wherein the amino acid sequence of said A33Rt is the sequence of SEQ ID NO:

3, the amino acid sequence of said B5Rt is the sequence of SEQ ID NO;

5, and the amino acid sequence of said L1R(185t) is the sequence of SEQ ID NO;

1.

54. A kit for treating a poxvirus infection in a human patient, said kit comprising an immunogenic amount of the soluble truncated poxvirus envelope protein of claim 48, said kit further comprising an applicator and an instructional material for the use of said kit.