Hpv e6 protein t cell epitopes and uses thereof

Abstract

The present invention is directed to the examination of the pattern of immunodominant T cell epitopes in the E6 protein of Human Papilloma virus and its further characterization in terms of its amino acid sequence and Human Leukocyte Antigen restriction. These epitopes are identified based on their ability to induce specific T cell responses and therefore, are important as sources of antigens for immunotherapies to treat cervical and other cancers. The present invention contemplates identifying a number of similar epitopes restricted by a wide variety of Human Leukocyte Antigen types so that they can be used together to develop preventative or therapeutic vaccines, which can be used for the general human population. The present invention also contemplates using E6 peptides of Human Papilloma virus as a diagnosis method to predict the probability of developing persistent cervical neoplasia in an individual.

What is claimed is: 
     
         1 . An immunogenic composition, comprising one or more synthetic peptides having a sequence at least 80% identical to a sequence that is SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein said synthetic peptides are acetylated at the amino terminus, amidated at the carboxyl terminus or acetylated at the amino terminus and amidated at the carboxyl terminus. 
     
     
         3 . The immunogenic composition of  claim 2 , wherein said composition contains a sequence at least 80% identical to SEQ ID NO: 32, a sequence at least 80% identical to SEQ ID NO: 33, a sequence at least 80% identical to SEQ ID NO: 34, a sequence having at least 80% identical to SEQ ID NO: 35, a sequence having at least 80% identical to SEQ ID NO: 36, and a sequence having at least 80% identical to SEQ ID NO: 37. 
     
     
         4 . The immunogenic composition of  claim 1 , further comprising an adjuvant. 
     
     
         5 . The immunogenic composition of  claim 4 , wherein said adjuvant comprises antigens from  Candida albicans , mumps, or  Trichophyton.   
     
     
         6 . The immunogenic composition of  claim 5 , wherein said adjuvant is concentrated whole cell extract made from lyophilized cells of  Candida albicans.   
     
     
         7 . The immunogenic composition of  claim 6 , wherein said adjuvant is contained in said composition in an antigen/adjuvant ratio of about 20 micrograms antigen per 200 microliter of adjuvant to about 20 micrograms antigen per 500 microliter of adjuvant. 
     
     
         8 . The immunogenic composition of  claim 7 , wherein said immunogenic composition is adapted to be administered intradermally. 
     
     
         9 . The immunogenic composition of  claim 1 , wherein said sequence(s) is expressed from a recombinant viral, vector or a plasmid, or is a chemically synthesized peptide. 
     
     
         10 - 26 . (canceled) 
     
     
         27 . An immunogenic composition comprising two or more peptides derived from epitopes of HPV E6 or E7 protein; and
 an adjuvant comprising antigens from  Candida albicans, mumps , or  Trichophyton.     
     
     
         28 . The immunogenic composition of  claim 27  wherein the peptides are derived from two or more immunodominant epitopes of HPV E6 or E7 protein effective to generate CD8 T-cell responses specific against the HPV. 
     
     
         29 . The immunogenic composition of  claim 27 , comprising one or more synthetic peptides having a sequence at least 80% identical to a sequence that is SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO. 3, SEQ ID NO. 4; SEQ ID NO. 5; SEQ ID NO. 6; SEQ ID NO. 7, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, or SEQ ID NO: 37; and
 an adjuvant comprising antigens from  Candida albicans, mumps , or  Trichophyton.     
     
     
         30 . The immunogenic composition of  claim 27 , wherein said adjuvant is concentrated whole cell extract made from lyophilized cells of  Candida albicans.   
     
     
         31 . The immunogenic composition of  claim 29 , wherein said adjuvant is concentrated whole cell extract made from lyophilized cells of  Candida albicans.   
     
     
         32 . The immunogenic composition of  claim 31 , wherein said adjuvant is contained in said composition in an antigen/adjuvant ratio of about 20 micrograms peptide antigen per 200 microliter of adjuvant to about 20 micrograms antigen per 500 microliter of adjuvant.