Inducing Cellular Immune Responses to Human Papillomavirus Using Peptide and Nucleic Acid Compositions

Abstract

This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to identify and prepare human papillomavirus (HPV) epitopes, and to develop epitope-based vaccines directed towards HPV. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use in the prevention and treatment of HPV infection.

1 . An isolated prepared human papilloma virus (HPV) epitope consisting of a sequence selected from the group consisting of the sequences set out in Tables VII-XX. 
     
     
         2 . A composition of  claim 1 , wherein the epitope is admixed or joined to a CTL epitope. 
     
     
         3 . A composition of  claim 2 , wherein the CTL epitope is selected from the group set out in  claim 1 . 
     
     
         4 . A composition of  claim 1 , wherein the epitope is admixed or joined to an HTL epitope. 
     
     
         5 . A composition of  claim 4 , wherein the HTL epitope is selected from the group set out in  claim 1 . 
     
     
         6 . A composition of  claim 4 , wherein the HTL epitope is a pan-DR binding molecule. 
     
     
         7 . A composition of  claim 1 , comprising at least three epitopes selected from the group set out in  claim 1 . 
     
     
         8 . A composition of  claim 1 , further comprising a liposome, wherein the epitope is on or within the liposome. 
     
     
         9 . A composition of  claim 1 , wherein the epitope is joined to a lipid. 
     
     
         10 . A composition of  claim 1 , wherein the epitope is joined to a linker. 
     
     
         11 . A composition of  claim 1 , wherein the epitope is bound to an HLA heavy chain, β2-microglobulin, and strepavidin complex, whereby a tetramer is formed. 
     
     
         12 . A composition of  claim 1 , further comprising an antigen presenting cell, wherein the epitope is on or within the antigen presenting cell. 
     
     
         13 . A composition of  claim 12 , wherein the epitope is bound to an HLA molecule on the antigen presenting cell, whereby when a cytotoxic lymphocyte (CTL) is present that is restricted to the HLA molecule, a receptor of the CTL binds to a complex of the HLA molecule and the epitope. 
     
     
         14 . A clonal cytotoxic T lymphocyte (CTL), wherein the CTL is cultured in vitro and binds to a complex of an epitope selected from the group set out in Tables VII-XVIII, bound to an HLA molecule. 
     
     
         15 . A peptide comprising at least a first and a second epitope, wherein the first epitope is selected from the group consisting of the sequences set out in Tables VII-XX;
 wherein the peptide comprise less than 50 contiguous amino acids that have 100% identity with a native peptide sequence.   
     
     
         16 . A composition of  claim 15 , wherein the first and the second epitope are selected from the group of  claim 14 . 
     
     
         17 . A composition of  claim 16 , further comprising a third epitope selected from the group of  claim 15 . 
     
     
         18 . A composition of  claim 15 , wherein the peptide is a heteropolymer. 
     
     
         19 . A composition of  claim 15 , wherein the peptide is a homopolymer. 
     
     
         20 . A composition of  claim 15 , wherein the second epitope is a CTL epitope. 
     
     
         21 . A composition of  claim 15 , wherein the second epitope is a PanDR binding molecule. 
     
     
         22 . A composition of  claim 1 , wherein the first epitope is linked to a linker sequence. 
     
     
         23 . A vaccine composition comprising:
 a unit dose of a peptide that comprises less than 50 contiguous amino acids that have 100% identity with a native peptide sequence of HPV, the peptide comprising at least a first epitope selected from the group consisting of the sequences set out in Tables VII-XX; and;   a pharmaceutical excipient.   
     
     
         24 . A vaccine composition in accordance with  claim 23 , further comprising a second epitope. 
     
     
         25 . A vaccine composition of  claim 23 , wherein the second epitope is a PanDR binding molecule. 
     
     
         26 . A vaccine composition of  claim 23 , wherein the pharmaceutical excipient comprises an adjuvant. 
     
     
         27 . An isolated nucleic acid encoding a peptide comprising an epitope consisting of a sequence selected from the group consisting of the sequences set out in Tables VII-XX. 
     
     
         28 . An isolated nucleic acid encoding a peptide comprising at least a first and a second epitope, wherein the first epitope is selected from the group consisting of the sequences set out in Tables VII-XX; and wherein the peptide comprises less than 50 contiguous amino acids that have 100% identity with a native peptide sequence. 
     
     
         29 . An isolated nucleic acid of  claim 28 , wherein the peptide comprises at least two epitopes selected from the sequences set out in Tables VII-XX. 
     
     
         30 . An isolated nucleic acid of  claim 29 , wherein the peptide comprises at least three epitopes selected from the sequences set out in Tables VII-XX. 
     
     
         31 . An isolated nucleic acid of  claim 28 , wherein the second peptide is a CTL epitope. 
     
     
         32 . An isolated nucleic acid of  claim 20 , wherein the second peptide is an HTL epitope.