Epitopes of hepatitis C virus

Abstract

The invention provides compositions containing HCV epitopes, which are recognized by cytotoxic T lymphocytes. Such polypeptides are used in prophylactic vaccines, immunotherapies, and assays to monitor the progress or success of immune interventions. The compositions are optimized to elicit an immune response in a genetically-diverse population of individuals.

1 . An immunogenic composition comprising a plurality of immunodominant Hepatitis C Virus (HCV) polypeptides, wherein said polypeptides bind to a spectrum of HLA class I molecules which are expressed in at least 85% of the individuals in a target population.  
     
     
         2 . The immunogenic composition of  claim 1 , wherein said polypeptides bind to a spectrum of HLA class I molecules which are expressed in at least 95% of the individuals in a target population.  
     
     
         3 . The immunogenic composition of  claim 1 , wherein said polypeptides bind to a spectrum of HLA class I molecules which are expressed in at least 99% of the individuals in a target population.  
     
     
         4 . An immunogenic composition comprising a plurality of purified immunodominant Hepatitis C Virus (HCV) polypeptides, wherein said polypeptides bind to a plurality of HLA class I molecules.  
     
     
         5 . The composition of  claim 4 , wherein at least one polypeptide binds to an HLA-A class I molecule and wherein said HLA-A class I molecule is not HLA A2.  
     
     
         6 . The composition of  claim 4 , wherein at least one polypeptide binds to an HLA-B class I molecule.  
     
     
         7 . The composition of  claim 4 , wherein at least one polypeptide binds to an HLA-C class I molecule.  
     
     
         8 . The composition of  claim 4 , wherein at least one polypeptide binds to an HLA class I molecule selected from the group consisting of Cw7, A1, and B55.  
     
     
         9 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of a naturally-occurring HCV protein region selected from the group consisting of Core, E, NS3, NS4, and NS5.  
     
     
         10 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of an HCV E2 protein.  
     
     
         11 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of an HCV NS3 protein.  
     
     
         12 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of an HCV NS5A protein.  
     
     
         13 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of an HCV NS5B protein.  
     
     
         14 . The composition of  claim 4 , wherein the amino acid sequence of at least one polypeptide comprises at least 8 contiguous amino acids of an HCV P7 protein.  
     
     
         15 . A composition comprising a polypeptide, said polypeptide being less than 50 amino acids in length, wherein the amino acid sequence of said polypeptide comprises the amino acid sequence of SEQ ID NO:42, 43, 44, 45, 46, 47, or 48.  
     
     
         16 . A composition comprising a polypeptide, wherein the amino acid sequence of said polypeptide consists essentially of the amino acid sequence of SEQ ID NO:42, 43, 44, 45, 46, 47, or 48.  
     
     
         17 . A composition comprising a polypeptide, wherein the amino acid sequence of said polypeptide consists essentially of the amino acid sequence of SEQ ID NO:42, 45, 47, or 48.  
     
     
         18 . A composition comprising a polypeptide, wherein the amino acid sequence of said polypeptide consists essentially of the amino acid sequence of SEQ ID NO:43, 44, or 46.  
     
     
         19 . A composition comprising a polypeptide, said polypeptide being less than 50 amino acids in length, wherein said amino acid sequence of said polypeptide consists essentially of the amino acid sequence of SEQ ID NO: 49, 50, 51, 52, 53, 54, 55, 56, 57, or 58.  
     
     
         20 . A composition comprising a polypeptide, wherein said amino acid sequence of said polypeptide consists essentially of the amino acid sequence of SEQ ID NO: 49, 50, 51, 52, 53, 54, 55, 56, 57, or 58.  
     
     
         21 . A method of stimulating an HCV-specific immune response, comprising contacting a T cell with an immunogen comprising a peptide epitope selected from the group consisting of SEQ ID NO: 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, and 58.  
     
     
         22 . The method of  claim 21 , wherein said T cell is CD8+.  
     
     
         23 . The method of  claim 21 , wherein said T cell is contacted ex vivo.  
     
     
         24 . A method of stimulating an HCV-specific immune response, comprising administering to a mammal an immunogen comprising a peptide epitope selected from the group consisting of SEQ ID NO: 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, and 58, wherein said immune response comprises an increase in proliferation of HCV-specific early memory CD8+ T cells.  
     
     
         25 . A method for measuring an immune response in a patient, comprising 
 (a) providing a sample of cytotoxic T lymphocyte effector cells from a patient, said patient having been immunized with the composition of  claim 1;     (b) providing HLA class I matched detectably-labeled target cells, said target cells having been pulsed with said polypeptide;    (c) contacting the effector cells and target cells; and    (d) determining the amount of label released by said target cells, wherein an increase in the amount of label released compared to a control value indicates the presence of an HCV-specific immune response in said patient.    
     
     
         26 . A method of identifying an immunodominant HCV epitope, comprising 
 (a) providing a patient-derived population of lymphocytes, said patient being infected with HCV or having been infected in the past;    (b) contacting said population with an HCV protein matrix; and    (c) measuring a CTL response, wherein an increase in said response in a region of said matrix indicates that said region contains an immunodominant HCV epitope.