MHC Class I Associated Hepatitis B Peptides

Abstract

The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of Hepatitis B virus (HBV) infection, and discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against HBV infection. The peptide and/or proteins of the invention may be used as a therapeutic drug to stimulate the immune system to recognize and eliminate HBV infection in infected cells or as a vaccine for the prevention of disease.

1 . A pharmaceutical composition comprising a polypeptide, oligopeptide or peptide consisting of 8 to about 30 amino acid residues and comprising a sequence that is selected from the group consisting of:
 (i) SEQ ID NO: 1, 3, and 5 to 17; and   (ii) an amino acid sequence that differs from SEQ ID NO: 1, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 by no more than one amino acid unit;   wherein said polypeptide, oligopeptide or peptide binds to one or more class I MHC alleles or can be processed to bind to one or more class I MHC alleles and activate a T lymphocyte.   
     
     
         2 . The pharmaceutical composition of  claim 1  wherein said polypeptide, oligopeptide or peptide comprises at least two epitopic peptides. 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein said polypeptide, oligopeptide or peptide comprises at least three epitopic peptides. 
     
     
         4 . The pharmaceutical composition of  claim 1  wherein said polypeptide, oligopeptide or peptide comprises at least four epitopic peptides. 
     
     
         5 . A polynucleotide selected from the group consisting of: (a) a polynucleotide that encodes an oligopeptide or peptide of  claim 1 , and (b) the full complement of (a). 
     
     
         6 . The polynucleotide of  claim 5 , wherein the polynucleotide of (a) is DNA. 
     
     
         7 . The polynucleotide of  claim 5 , wherein the polynucleotide of (a) is RNA. 
     
     
         8 . A method for vaccinating and treating a subject for HBV infection, said infected cells expressing any class I MHC molecule, comprising administering to said subject a composition that binds to class I MHC molecules or can be processed to bind to class I MHC molecules comprising: at least one polypeptide comprising an epitopic peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17 in an amount sufficient to induce a CTL response to said infected cells; or at least one polypeptide comprising an epitopic peptide having no more than one amino acid difference from an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17 in an amount sufficient to induce a CTL response to said infected cells. 
     
     
         9 . A method for vaccinating and treating a subject with HBV infection, said infected cells expressing any class I MHC molecule, said method comprising administering to said subject a composition that binds to class I MHC molecules or can be processed to bind to class I MHC molecules comprising: a polynucleotide comprising a nucleic acid sequence encoding:
 at least one polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17 in an amount sufficient to induce a CTL response to said infected cells; or   at least one polypeptide comprising an epitopic peptide comprising no more than one amino acid difference from an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17 in an amount sufficient to induce a CTL response to said infected cells.   
     
     
         14 . A method for generating an immune response ex vivo using T cells from a subject infected with HBV, said method comprising: stimulating the production of CTL response for use in passive immunotherapy, wherein said T cells react with at least one polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17; or at least one polypeptide comprising no more than one amino acid difference from an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17. 
     
     
         15 . The method of  claim 14 , wherein said method is a T cell adoptive therapy generated from autologous or HLA matched subjects. 
     
     
         16 . A method for assessing or diagnosing an immune response in a subject infected with HBV or vaccinated for HBV and related viruses said method comprising: stimulating the production of CTL response, wherein said T cells react with at least one polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17; or at least one polypeptide comprising no more than one amino acid difference from an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 3, and 5 to 17. 
     
     
         17 . A method for vaccinating humans against HBV infection using the pharmaceutical composition of  claim 1 .