Vaccine for treatment and prevention of herpes simplex virus infection

Abstract

The present invention relates to methods and compositions for the prevention and treatment of herpes virus infections. The invention provides antigenic peptides, and pharmaceutical compositions comprising complexes of antigenic peptides and adjuvants that can activate an immune response against herpes viruses. The invention also provides methods of making the antigenic peptides and complexes of antigenic peptides and adjuvants. Methods of use of the pharmaceutical compositions are also provided.

1 - 48 . (canceled) 
     
     
         49 . A method of reducing viral shedding of HSV-1 or HSV-2 in an infected individual, the method comprising administering to the individual an effective amount of a composition that comprises at least ten different purified complexes of a stress protein noncovalently bound to an antigenic peptide, wherein said complexes each comprise a different antigenic peptide, and wherein each one of said different antigenic peptides comprises one or more HLA-binding epitopes of a different herpesvirus peptide selected from among herpesvirus peptides differing in amino acid sequence, wherein for ten of said complexes the amino acid sequence of each herpesvirus peptide is selected from the group consisting of SEQ ID NO: 3, 9, 21, 34, 35, 36, 37, 41, 42, and 44, wherein each one of said different antigenic peptides does not comprise the entire amino acid sequence of a herpes simplex virus protein, thereby reducing viral shedding of the HSV-1 or HSV-2 in the individual. 
     
     
         50 . The method of  claim 49 , wherein said viral shedding is genital viral shedding. 
     
     
         51 . The method of  claim 49 , wherein the stress protein is a member of the hsp60, hsp70, or hsp90 family of stress proteins. 
     
     
         52 . The method of  claim 49 , wherein the stress protein is hsc70, Hsp70, hsp90, hsp110, grp170, gp96, calreticulin, or combinations of two or more thereof. 
     
     
         53 . The method of  claim 52 , wherein the stress protein is Hsp70 or hsc70. 
     
     
         54 . The method of  claim 49 , wherein the stress protein is a human stress protein. 
     
     
         55 . The method of  claim 49 , wherein the composition further comprises one or more adjuvants. 
     
     
         56 . The method of  claim 55 , wherein the adjuvant is a saponin or an immunostimulatory nucleic acid. 
     
     
         57 . The method of  claim 49 , further comprising administering to the individual an adjuvant, an antibody, a biological response modifier, or a chemotherapeutic agent. 
     
     
         58 . The method of  claim 57 , wherein said chemotherapeutic agent is chosen from the group consisting of acyclovir, valacyclovir, pencyclovir, famcyclovir, cidofovir, and phosphonoformic acid, and combinations thereof. 
     
     
         59 . The method of  claim 58 , wherein said biological response modifier is IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IFNα, IFN-β, IFN-γ, TNFα, TNF β, G-CSF, GM-CSF, or TGF β. 
     
     
         60 . The method of  claim 49 , wherein the individual is a human. 
     
     
         61 . The method of  claim 49 , wherein the composition is administered to the individual biweekly. 
     
     
         62 . The method of  claim 49 , wherein the composition is administered to the individual by intradermal, subcutaneous, or mucosal administration. 
     
     
         63 . The method of  claim 49 , wherein the composition further comprises at least one other purified complex of a stress protein noncovalently bound to an antigenic peptide, wherein the antigenic peptide of the at least one other purified complex comprises one or more HLA-binding epitopes of a herpesvirus peptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 4-8, 16-18, 20, 23-25, 29, 33, 38, 39, 43, and 45-49. 
     
     
         64 . The method of  claim 63 , wherein the composition further comprises QS-21. 
     
     
         65 . The method of  claim 64 , wherein the amount of the stress protein in the composition is in a range of 10 μg to 600 μg. 
     
     
         66 . The method of  claim 65 , wherein the amount of the QS-21 in the composition is 10 μg, 25 μg, or 50 μg. 
     
     
         67 . The method of  claim 49 , wherein, prior to administering the immunogenic amount of the composition, antibodies against an HSV antigen are detectable in serum from the individual. 
     
     
         68 . A method of reducing transmission of HSV-1 or HSV-2 from an infected individual, the method comprising administering to the individual an effective amount of a composition that comprises at least ten different purified complexes of a stress protein noncovalently bound to an antigenic peptide, wherein said complexes each comprise a different antigenic peptide, and wherein each one of said different antigenic peptides comprises one or more HLA-binding epitopes of a different herpesvirus peptide selected from among herpesvirus peptides differing in amino acid sequence, wherein for ten of said complexes the amino acid sequence of each herpesvirus peptide is selected from the group consisting of SEQ ID NO: 3, 9, 21, 34, 35, 36, 37, 41, 42, and 44, wherein each one of said different antigenic peptides does not comprise the entire amino acid sequence of a herpes simplex virus protein, thereby reducing transmission of the HSV-1 or HSV-2 from the individual. 
     
     
         69 . A method of reducing the frequency of outbreaks of herpes caused by HSV-1 or HSV-2 in an infected individual, the method comprising administering to the individual an effective amount of a composition that comprises at least ten different purified complexes of a stress protein noncovalently bound to an antigenic peptide, wherein said complexes each comprise a different antigenic peptide, and wherein each one of said different antigenic peptides comprises one or more HLA-binding epitopes of a different herpesvirus peptide selected from among herpesvirus peptides differing in amino acid sequence, wherein for ten of said complexes the amino acid sequence of each herpesvirus peptide is selected from the group consisting of SEQ ID NO: 3, 9, 21, 34, 35, 36, 37, 41, 42, and 44, wherein each one of said different antigenic peptides does not comprise the entire amino acid sequence of a herpes simplex virus protein, thereby reducing the frequency of outbreaks of herpes caused by HSV-1 or HSV-2 in the individual.