Immunological herpes simplex virus antigens and methods for use thereof
View Patent ↗The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection. Disclosed herein are antigens and/or their constituent epitopes confirmed to be recognized by T-cells derived from herpetic lesions or from uterine cervix. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.
1. A pharmaceutical composition comprising an isolated herpes simplex virus (HSV) polypeptide, wherein the polypeptide consists of amino acids 105-126, 125-146, 187-206, 105-190 or 177-220 of U L 49 protein, and a pharmaceutically acceptable carrier.
2. The composition of claim 1 , wherein the polypeptide is a fusion protein.
3. The composition of claim 2 , wherein the fusion protein is soluble.
4. A polynucleotide that encodes a polypeptide consisting essentially of:
amino acids 105-126, 125-146, 187-206, 105-190 or 177-220 of U L 49.
5. A vector comprising the polynucleotide of claim 4 .
6. A host cell transformed with the vector of claim 5 .
7. A method of producing an HSV polypeptide comprising culturing the host cell of claim 6 and recovering the polypeptide so produced.
8. An HSV polypeptide produced by the method of claim 7 .
9. A pharmaceutical composition comprising the polynucleotide of claim 4 and a pharmaceutically acceptable carrier.
10. A recombinant virus genetically modified to express the polypeptide of claim 8 .
11. The recombinant virus of claim 10 which is a vaccinia virus, canary pox virus, lentivirus, retrovirus, herpes virus or adenovirus.
12. A pharmaceutical composition comprising the virus of claim 11 and a pharmaceutically acceptable carrier.
13. A method of treating an HSV infection in a subject comprising administering the composition of claim 1 to the subject.
14. A method of treating an HSV infection in a subject comprising administering the pharmaceutical composition of claim 9 to the subject.
15. The pharmaceutical composition of claim 1 , further comprising an adjuvant.
16. The pharmaceutical composition of claim 9 , further comprising an adjuvant.
17. The pharmaceutical composition of claim 12 , further comprising an adjuvant.
18. A method of enhancing the production of HSV-specific antibodies in a subject comprising administering to the subject an isolated polypeptide that consists of amino acids 105-126, 125-146, 187-206, 105-190 or 177-220 of U L 49.
19. A recombinant non-HSV virus genetically modified to express a polypeptide that consists of amino acids 105-126, 125-146, 187-206, 105-190 or 177-220 of U L 49 protein.
20. The recombinant non-HSV virus of claim 19 which is a vaccinia virus, canary pox virus, lentivirus, retrovirus, herpes virus or adenovirus.
21. A pharmaceutical composition comprising the non-HSV virus of claim 19 and a pharmaceutically acceptable carrier, wherein the virus is a vaccinia virus or a canary pox virus.
22. The pharmaceutical composition of claim 21 , further comprising an adjuvant.
23. A fusion protein comprising an HSV polypeptide fused to a heterologous polypeptide, wherein the HSV polypeptide consists essentially of amino acids 105-126, 125-146, 187-206, 105-190 or 177-220 of U L 49.
24. A fusion protein of claim 23 that is soluble.
25. A polynucleotide that encodes a fusion protein of claim 23 .
26. A vector comprising the polynucleotide of claim 25 .
27. A host cell transformed with the vector of claim 26 .
28. A method of producing a fusion protein comprising culturing the host cell of claim 27 and recovering the fusion protein so produced.
29. A fusion protein produced by the method of claim 28 .
30. A fusion protein of claim 29 that is soluble.
31. A pharmaceutical composition comprising the fusion protein of claim 23 , and a pharmaceutically acceptable carrier.
32. The pharmaceutical composition of claim 31 , further comprising an adjuvant.
33. A pharmaceutical composition comprising the fusion protein of claim 29 , and a pharmaceutically acceptable carrier.
34. The pharmaceutical composition of claim 33 , further comprising an adjuvant.