Herpes simplex virus combined subunit vaccines and methods of use thereof
View Patent ↗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 impeding immune evasion by HSV thereby vaccinating a subject against HSV and treating, suppressing, inhibiting, and/or reducing an incidence of 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 (HSV)-2 glycoprotein D (gD) protein or immunogenic fragment thereof; and
b. a recombinant HSV-2 glycoprotein C (gC) protein fragment, wherein said fragment comprises a C3b-binding domain thereof, or an immunogenic fragment of said C3b-binding domain;
wherein administration of said composition to a human subject elicits an anti HSV-2 gC antibody that blocks an immune evasion function of said recombinant HSV gC protein.
2. The composition of claim 1 , further comprising a recombinant HSV-1 protein selected from a gD-1 protein, a gC-1 protein, and a gE-1 protein.
3. The composition of claim 1 , further comprising an adjuvant.
4. The composition of claim 3 , wherein said adjuvant comprises a CpG-containing nucleotide molecule, an aluminum salt adjuvant, or a combination thereof.
5. A method of inducing an anti-HSV-2 immune response in a subject, the method comprising the step of administering to said subject the composition of claim 1 .
6. The method of claim 5 further comprising the step of administering to said subject a booster immunization, wherein said booster immunization comprises a recombinant HSV-2 gD protein or immunogenic fragment thereof.
7. The method of claim 6 , wherein said recombinant HSV-2 gD protein or immunogenic fragment thereof is present in said booster immunization an amount of 2-10 micrograms per dose.
8. A method of treating, suppressing, inhibiting, or reducing an incidence of an Herpes Simplex Virus (HSV)-2 infection in a subject, the method comprising the step of administering to said subject an immunogenic composition comprising (a) a recombinant HSV-2 glycoprotein D (gD) protein or immunogenic fragment thereof; and (b) a recombinant HSV-2 glycoprotein C (gC) protein fragment, wherein said fragment comprises a C3b-binding domain thereof, or an immunogenic fragment of said C3b-binding domain, wherein administration of said composition elicits an anti-HSV-2 gC antibody that blocks an immune evasion function of said recombinant HSV gC protein.
9. The method of claim 8 , wherein said HSV-2 infection is a primary HSV-2 infection.
10. The method of claim 8 , wherein said HSV-2 infection is a flare, recurrence, or HSV labialis following a primary HSV infection.
11. The method of claim 8 , wherein said HSV-2 infection is a genital HSV-2 infection.
12. The method of claim 8 , wherein said HSV-2 infection is an oral HSV-2 infection.
13. The method of claim 8 , wherein said composition is administered intramuscularly.
14. The method of claim 8 , wherein said composition is administered before exposure to HSV-2.
15. The method of claim 10 , wherein said composition is administered after exposure to HSV-2.
16. The method of claim 8 further comprising the step of administering to said subject a booster immunization, wherein said booster immunization comprises said recombinant HSV-2 gD protein or immunogenic fragment thereof.
17. The method of claim 16 , wherein said recombinant HSV gD protein or immunogenic fragment thereof is present in said booster immunization an amount of 2-10 micrograms per dose.
18. The method of claim 8 , wherein said HSV-2 infection is a reactivation of a latent HSV infection.
19. The method of claim 8 , wherein said composition further comprises an adjuvant.