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. The present disclosure provides, inter alia, certain highly effective vaccines and immunogenic compositions against HSV-2. The antigens can be used therapeutically or prophylactically.
1. A vaccine formulation comprising a pharmaceutically-acceptable carrier and an HSV-2 gD2 polypeptide, wherein the gD2 polypeptide has an internal deletion of all or part of a transmembrane domain.
2. The vaccine formulation of claim 1 , further comprising an HSV-2 ICP4 polypeptide or an immunogenic fragment comprising at least 8 contiguous amino acids of an HSV-2 ICP4 polypeptide.
3. A vaccine formulation comprising a pharmaceutically-acceptable carrier and a polypeptide comprising the amino acid sequence of SEQ ID NO:5 having an internal deletion of 8-23 contiguous amino acid residues selected from amino acid residues 340-363 of SEQ ID NO:5.
4. The vaccine formulation of claim 3 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:5 having an internal deletion of 8-23 contiguous amino acid residues selected from amino acid residues 340-363 of SEQ ID NO:5.
5. The vaccine formulation of claim 3 , further comprising a second polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:1.
6. The vaccine formulation of claim 3 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:1 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:1.
7. The vaccine formulation of claim 5 , wherein the second polypeptide consists of an amino acid sequence having at least 90% identity to SEQ ID NO:1.
8. The vaccine formulation of claim 6 , wherein the second polypeptide consists of the amino acid sequence of SEQ ID NO:1 or an immunogenic fragment consisting of at least 8 contiguous amino acids of SEQ ID NO:1.
9. The vaccine formulation of claim 3 , further comprising a second polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:2.
10. The vaccine formulation of claim 3 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:2 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:2.
11. The vaccine formulation of claim 9 , wherein the second polypeptide consists of an amino acid sequence having at least 90% identity to SEQ ID NO:2.
12. The vaccine formulation of claim 10 , wherein the second polypeptide consists of the amino acid sequence of SEQ ID NO:2 or an immunogenic fragment consisting of at least 8 contiguous amino acids of SEQ ID NO:2.
13. A vaccine formulation comprising a pharmaceutically acceptable carrier and a polypeptide comprising the amino acid sequence of SEQ ID NO:4.
14. The vaccine formulation of claim 13 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:4.
15. The vaccine formulation of claim 13 , further comprising a second polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:1.
16. The vaccine formulation of claim 13 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:1 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:1.
17. The vaccine formulation of claim 15 , wherein the second polypeptide consists of an amino acid sequence having at least 90% identity to SEQ ID NO:1.
18. The vaccine formulation of claim 16 , wherein the second polypeptide consists of the amino acid sequence of SEQ ID NO:1 or an immunogenic fragment consisting of at least 8 contiguous amino acids of SEQ ID NO:1.
19. The vaccine formulation of claim 13 , further comprising a second polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:2.
20. The vaccine formulation of claim 13 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:2 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:2.
21. The vaccine formulation of claim 19 , wherein the second polypeptide consists of an amino acid sequence having at least 90% identity to SEQ ID NO:2.
22. The vaccine formulation of claim 20 , wherein the second polypeptide consists of the amino acid sequence of SEQ ID NO:2 or an immunogenic fragment consisting of at least 8 contiguous amino acids of SEQ ID NO:2.
23. A vaccine formulation comprising a pharmaceutically-acceptable carrier and a polypeptide comprising the amino acid sequence of SEQ ID NO:4 having a deletion of 1-20 amino acid residues at the N-terminus, C-terminus, or both, of SEQ ID NO:4.
24. The vaccine formulation of any one of claim 5 , 9 , 15 , or 19 , further comprising a third polypeptide comprising SEQ ID NO:3 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:3.
25. A vaccine formulation comprising a pharmaceutically-acceptable carrier, an adjuvant comprising one or more purified fractions of quillaja saponins, a first polypeptide comprising the amino acid sequence of SEQ ID NO:4 and a second polypeptide comprising the amino acid sequence of SEQ ID NO:1 or an immunogenic fragment comprising at least 8 contiguous amino acids of SEQ ID NO:1.
26. A method of treating a subject suffering from or susceptible to HSV-2 infection, comprising administering to the subject an effective amount of the vaccine formulation of any one of claim 3 , 5 , 9 , 13 , 15 , or 19 , thereby treating the subject.
27. The method of claim 26 , wherein administering the vaccine formulation reduces symptoms of HSV-2, reduces frequency of recurrences of HSV-2 outbreaks in the subject, or reduces shedding and transmission of HSV-2.
28. A vaccine formulation comprising a pharmaceutically-acceptable carrier, a first polypeptide comprising the amino acid sequence of SEQ ID NO:4, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:2.
29. The vaccine formulation of claim 28 , wherein the first polypeptide consists of the amino acid sequence of SEQ ID NO:4 and the second polypeptide consists of the amino acid sequence of SEQ ID NO:2.
30. The vaccine formulation of claim 28 or 29 , further comprising an adjuvant.