Immune responses against hpv antigens elicited by compositions comprising an hpv antigen and a stress protein or an expression vector capable of expression of these proteins

Abstract

This document describes compositions and methods for inducing an immune response (e.g., a cellular response such as a cell-mediated cytolytic immune response) to a human papillomavirus (HPV) antigen, which can be displayed by HPV or exhibited by infected cells (e.g., cells from cervical and other tumors). The HPV protein can be joined to a stress protein by chemical conjugation or noncovalently using linking moieties, or by fusion (e.g., a recombinant fusion protein). Also described are expression vectors containing sequences encoding HPV antigens and stress proteins, which can be introduced into cells of a subject or cells ex vivo. Also described are compositions that include a stress protein linked to an HPV antigen and another pharmacologically acceptable component and stress protein —HPV antigen fusions and conjugates. These compositions can be used to induce or enhance an immune response against HPV and cells that exhibit HPV antigens, including HPV-associated tumors.

1 . A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an HPV protein antigen joined to a stress protein.  
     
     
         2 . The composition of  claim 1  wherein the immune response is a cellular immune response.  
     
     
         3 . The composition of  claim 1  wherein the stress protein is a mycobacterial stress protein.  
     
     
         4 . The composition of  claim 1  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         5 . The composition of  claim 1  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         6 . A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an HPV protein antigen conjugated to a stress protein.  
     
     
         7 . The composition of  claim 6  wherein the immune response is a cellular immune response.  
     
     
         8 . The composition of  claim 6  wherein the stress protein is a mycobacterial stress protein.  
     
     
         9 . The composition of  claim 6  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         10 . The composition of  claim 6  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         11 . A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising a fusion protein comprising an HPV protein antigen fused to a stress protein.  
     
     
         12 . The composition of  claim 11  wherein the immune response is a cellular immune response.  
     
     
         13 . The composition of  claim 11  wherein the stress protein is a mycobacterial stress protein.  
     
     
         14 . The composition of  claim 11  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         15 . The composition of  claim 11  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         16 . A composition comprising an HPV protein antigen joined to a stress protein in combination with another pharmacologically acceptable component.  
     
     
         17 . The composition of  claim 16  wherein the stress protein is a mycobacterial stress protein.  
     
     
         18 . The composition of  claim 16  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         19 . The composition of  claim 16  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         20 . A conjugate comprising an HPV protein antigen conjugated to a stress protein.  
     
     
         21 . The conjugate of  claim 20  wherein the stress protein is a mycobacterial stress protein.  
     
     
         22 . The conjugate of  claim 20  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         23 . The conjugate of  claim 20  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         24 . A fusion protein comprising an HPV protein antigen fused to a stress protein.  
     
     
         25 . The fusion protein of  claim 24  wherein the stress protein is a mycobacterial stress protein.  
     
     
         26 . The fusion protein of  claim 24  wherein the HPV protein antigen is the E6 or the E7 protein.  
     
     
         27 . The fusion protein of  claim 24  wherein the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         28 . The fusion protein of  claim 24  wherein the HPV protein antigen is E6 or E7 and the stress protein is from the Hsp60 or the Hsp70 family.  
     
     
         29 . A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an expression vector encoding and capable of directing expression of the fusion protein of  claim 24  in cells of the subject.  
     
     
         30 . The composition of  claim 29  wherein the immune response is a cellular immune response.  
     
     
         31 . A composition for inducing an immune response against an HPV protein antigen in a subject, the composition comprising an expression vector encoding and capable of directing expression of the fusion protein of  claim 28  in cells of the subject.  
     
     
         32 . The composition of  claim 31  wherein the immune response is a cellular immune response.  
     
     
         33 . An expression vector encoding and capable of directing expression of the fusion protein of  claim 24  in cells of a subject.  
     
     
         34 . An expression vector encoding and capable of directing expression of the fusion protein of  claim 28  in cells of a subject.  
     
     
         35 . A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of  claim 33 .  
     
     
         36 . A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of  claim 34 .  
     
     
         37 . A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the composition of  claim 16 .  
     
     
         38 . A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the conjugate of  claim 20 .  
     
     
         39 . A method of inducing an immune response against an HPV protein antigen, comprising administering to a subject an effective amount of the fusion protein of  claim 24 .  
     
     
         40 . A method of treating a tumor exhibiting an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of  claim 33 .  
     
     
         41 . A method of treating a tumor exhibiting an HPV protein antigen, comprising administering to a subject an effective amount of the expression vector of  claim 34 .  
     
     
         42 . A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the composition of  claim 16 .  
     
     
         43 . A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the conjugate of  claim 20 .  
     
     
         44 . A method of treating a tumor expressing an HPV protein antigen, comprising administering to a subject an effective amount of the fusion protein of  claim 24.