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 . A composition, comprising a plurality of—different antigenic peptides, 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. 
     
     
         2 . A composition comprising a plurality of—different purified complexes of a stress protein noncovalently bound to an antigenic peptide, wherein said plurality of different 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. 
     
     
         3 . (canceled) 
     
     
         4 . A composition prepared by a method comprising complexing in vitro a stress protein with at least 20, 30, or 40 different antigenic peptides, 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. 
     
     
         5 . (canceled) 
     
     
         6 . The composition of  claim 2 , wherein the stress protein is a member of the hsp60, hsp70, or hsp90 family of stress proteins. 
     
     
         7 . The composition of  claim 2 , wherein the stress protein is hsc70, hsp70, or hsp90, hspl 10, grp 170, gp96, calreticulin, or combinations of two or more thereof. 
     
     
         8 . The composition of  claim 2 , wherein the stress protein is a human stress protein. 
     
     
         9 . The composition of  claim 1 , wherein the composition further comprises an antibody. 
     
     
         10 . The composition of  claim 1 , wherein the composition further comprises a biological response modifier. 
     
     
         11 . The composition of  claim 10 , wherein the biological response modifier is IL-1α, IL-1p, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IFNα, IFNβ, IFN-γ, TNFα, TNFβ, G-CSF, GM-CSF, or TGFβ. 
     
     
         12 . The composition of  claim 1 , wherein the composition further comprises a chemotherapeutic agent. 
     
     
         13 . The composition of  claim 12 , wherein the chemotherapeutic agent is acyclovir, valacyclovir, pencyclovir, famcyclovir, cidofovir, phosphonoformic acid, or combinations thereof. 
     
     
         14 . The composition of  claim 1 , wherein the composition further comprises an adjuvant. 
     
     
         15 . The composition of  claim 14  wherein the adjuvant is a saponin or an immunostimulatory nucleic acid. 
     
     
         16 . A pharmaceutical composition comprising immunogenic amounts of the composition of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         17 . A kit comprising a first container comprising the composition of  claim 1  and at least one container comprising an adjuvant, a chemotherapeutic agent, an antibody, or a biological response modifier. 
     
     
         18 . A method for preparing a composition for eliciting in a mammal an immune response against HSV-1 or HSV-2, said method comprising complexing in vitro stress proteins to a plurality of different antigenic peptides, wherein each one of said different antigenic peptides comprises one or more HLA-binding epitopes of a different herpesvirus peptide selected from among herpesvirus peptide differing in amino acid sequence. 
     
     
         19 . The method of  claim 18  further comprising combining a pharmaceutical carrier with the plurality of different complexes. 
     
     
         20 . (canceled) 
     
     
         21 . A method of eliciting an immune response against HSV-1 or HSV-2 in an individual, the method comprising administering to the individual an immunogenic amount of the composition of  claim 1 . 
     
     
         22 . A method of treating an infection by a herpesvirus in an individual having said infection, comprising administering to the individual a therapeutically effective amount of the composition of  claim 1 . 
     
     
         23 . A method of preventing an infection by a herpesvirus in an individual in whom preventing said infection is desired, comprising administering to the individual a prophylactically effective amount of the composition of  claim 1 . 
     
     
         24 - 48 . (canceled)