Nucleic acid vaccines against herpes simplex virus type 2: compositions and methods for eliciting an immune response
Herpes Simplex Virus-2 (HSV-2) infection is a major health concern. Highly effective vaccines and immunogenic compositions against HSV-2 which can be used therapeutically or prophylactically, are described.
1. An immunogenic composition comprising a pharmaceutically-acceptable carrier, an adjuvant, and a nucleic acid comprising a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1.
2. The immunogenic composition of claim 1 , wherein the polypeptide lacks 1-20 amino acids at one or both termini of SEQ ID NO:1.
3. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises at least one additional nucleic acid having a nucleotide sequence that encodes a polypeptide having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NOS: 1, 3, 5, 38, or 138.
4. The immunogenic composition of claim 3 , wherein said at least one additional nucleic acid encodes a polypeptide having an amino acid sequence at least 85% identical to SEQ ID NO: 3.
5. The immunogenic composition of claim 1 , wherein the adjuvant is a protein.
6. The immunogenic composition of claim 5 , wherein the protein is a cytokine.
7. The immunogenic composition of claim 1 , wherein the adjuvant is a nucleic acid encoding a cytokine.
8. The immunogenic composition of claim 6 , wherein the cytokine is an interleukin.
9. The immunogenic composition of claim 8 , wherein the interleukin is interleukin-12.
10. An immunogenic composition comprising:
a) a pharmaceutically-acceptable carrier,
b) a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1; and
c) at least one additional nucleic acid having a nucleotide sequence that encodes a polypeptide having SEQ ID NOS: 1, 3, 5, 38, or 138, or an immunogenic fragment thereof.
11. The immunogenic composition of claim 10 , wherein the at least one additional nucleic acids encode polypeptides having SEQ ID NOS: 1 and 3, or an immunogenic fragment thereof.
12. The immunogenic composition of claim 1 , wherein the nucleic acid is cDNA.
13. The immunogenic composition of claim 1 , wherein the nucleic acid is DNA.
14. The immunogenic composition of claim 1 , wherein the nucleic acid is a portion of a plasmid.
15. A treatment regimen comprising:
(i) a first immunogenic composition comprising a pharmaceutically-acceptable carrier and a nucleic acid comprising a nucleotide sequence that encodes a polypeptide comprising at least one of the polypeptides having an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1; and
(ii) a boost formulation to be administered subsequently comprising a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1, a nucleic acid comprising a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1, or a combination thereof.
16. The treatment regimen of claim 15 , wherein the boost formulation further comprises a polypeptide having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO:1 or 3 or a nucleic acid having a nucleotide sequence that encodes a polypeptide having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 1 or 3, or a combination thereof.
17. The treatment regimen of claim 15 , wherein the boost formulation further comprises a polypeptide having the amino acid sequence of SEQ ID NO: 2.
18. The treatment regimen of claim 15 , wherein the boost formulation further comprises a polypeptide having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 136 or a nucleic acid having a nucleotide sequence that encodes a polypeptide having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 3, or a combination thereof.
19. The treatment regimen of claim 15 , wherein the boost formulation comprises a polypeptide having an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1.
20. The treatment regimen of claim 15 , wherein the boost formulation comprises a nucleic acid comprising a nucleotide sequence that encodes a polypeptide having an amino acid sequence at least 90% identical to SEQ ID NO:1, wherein the polypeptide has an internal deletion of amino acids 390-544 of SEQ ID NO:1 and has an internal deletion of amino acids 786-820 of SEQ ID NO:1.
21. The treatment regimen of claim 15 , wherein the boost formulation comprises the same nucleic acids as the first immunogenic composition.
22. A method for inhibiting genital herpes in a subject, comprising administering an effective amount of an immunogenic composition according to claim 1 .
23. The method of claim 22 , wherein the method inhibits genital herpes in a subject after a three dose regimen.
24. The method of claim 22 , wherein the subject is a human.
25. The method of claim 22 , wherein the subject has not been previously infected with HSV-2.
26. A method for treating genital herpes in a subject, comprising administering an effective amount of an immunogenic composition according to claim 1 .
27. The method of claim 26 , wherein the method inhibits onset or reduces severity of genital herpes symptoms.
28. The method of claim 27 , wherein the method reduces the number of herpetic lesions.
29. The method of claim 28 , wherein the method reduces the number of days a subject experiences herpetic lesions.
30. The method of claim 26 or 27 , wherein the method increases the IgG titer to one or more HSV-2 antigens.
31. The method of claim 26 or 27 , wherein the method increases the T cell response to one or more HSV-2 antigens.
32. The method of claim 26 or 27 , wherein the method reduces the number of herpetic lesions at the onset of HSV-2 infection.
33. The method of claim 26 or 27 , wherein the method inhibits onset or reduces severity of genital herpes symptoms in a subject after a three dose regimen.
34. The method of claim 26 , wherein the subject is a human.
35. The method of claim 26 , wherein the subject has not been previously infected with HSV-2.