Herpes simplex virus combined subunit vaccines and methods of use thereof
This invention provides vaccines comprising two or more recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of vaccinating a subject against HSV and treating, impeding, inhibiting, reducing the incidence of, or suppressing an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.
1. An immunogenic composition comprising:
(a) a recombinant Herpes Simplex Virus-1 (HSV-1) glycoprotein D (gD) or immunogenic fragment thereof;
(b) a recombinant HSV-1 glycoprotein C (gC) fragment, wherein said gC fragment comprises amino acids 26-457 of SEQ ID NO: 3; and
(c) an adjuvant;
wherein the glycoprotein(s) of (a) and/or (b) is/are fused to an antigenic tag, and
wherein said immunogenic composition does not comprise HSV-1 glycoprotein B (gB).
2. The immunogenic composition of claim 1 , wherein said adjuvant comprises a CpG-containing nucleotide molecule, an aluminum salt adjuvant, or a combination thereof.
3. The immunogenic composition of claim 1 , wherein said recombinant HSV gD or immunogenic fragment thereof is present in an amount of 2-50 micrograms per dose.
4. The immunogenic composition of claim 1 , wherein said recombinant HSV gC fragment is present in an amount of 0.5-100 micrograms per dose.
5. A method of inducing an anti-HSV immune response in a subject, the method comprising the step of administering to said subject an effective amount of the immunogenic composition of claim 1 .
6. The method of claim 5 , further comprising the step of administering to said subject a booster vaccination.
7. The method of claim 6 , wherein said recombinant HSV gD protein or immunogenic fragment thereof is present in said booster vaccination in an amount of 2-50 micrograms per dose.
8. The method of claim 6 , wherein said booster vaccination comprises said recombinant HSV gD protein or immunogenic fragment thereof and does not comprise said recombinant HSV gC fragment.
9. A method of suppressing, inhibiting, or reducing an incidence of an HSV infection in a subject, the method comprising the step of administering to said subject an effective amount of the immunogenic composition of claim 1 .
10. The method of claim 9 , wherein said HSV infection is an HSV-1 infection.
11. The method of claim 9 , wherein said HSV infection is an HSV-2 infection.
12. The method of claim 9 , wherein said HSV infection is a primary HSV infection.
13. The method of claim 9 , wherein said HSV infection is a flare, recurrence, or HSV labialis following a primary HSV infection.
14. The method of claim 9 , wherein said HSV infection is HSV encephalitis.
15. The method of claim 9 , wherein said HSV infection is an HSV neonatal infection.
16. The method of claim 9 , wherein said subject is HIV-infected.
17. The immunogenic composition of claim 1 , wherein said gD fragment consists of amino acids 26-306 of SEQ ID NO: 1.
18. The immunogenic composition of claim 2 , wherein said adjuvant comprises a CpG-containing nucleotide molecule and an aluminum salt adjuvant.
19. The immunogenic composition of claim 1 , wherein said antigenic tag is a C-terminal His tag.