Prevention and treatment of HCV infection employing antibodies directed against conformational epitopes

Abstract

Conformational epitopes of the envelope protein E2 of the Hepatitis C virus (HCV) have been identified and characterized using a panel of monoclonal antibodies derived from patients infected with HCV. These conformational epitopes have been determined to be important in the immune response of humans to HCV and may be particularly important in neutralizing the virus. Based on the identification of these conformational epitopes, vaccines containing peptides and mimotopes with these conformational epitopes intact may be prepared and administered to patients to prevent and/or treat HCV infection. The identification of four distinct groups of monoclonal antibodies with each directed to a particular epitope of E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen.

1 .- 34 . (canceled)  
     
     
         35 . A peptide comprising a conformational epitope of E2 protein of HCV.  
     
     
         36 . The peptide of  claim 35  wherein the peptide does not contain the full sequence of the E2 protein of HCV.  
     
     
         37 . The peptide of  claim 35  comprising amino acids 411 through 644 of E2 of HCV 1b.  
     
     
         38 . The peptide of  claim 35  comprising an amino acid sequence of E2 of an HCV, wherein the amino acids are analogous to amino acids 411 through 644 of E2 of HCV 1b.  
     
     
         39 . The peptide of  claim 35  comprising amino acids 470 through 644 of HCV 1 b E2.  
     
     
         40 . A The peptide of  claim 35  comprising an amino acid sequence of E2 of an HCV, wherein the amino acids are analogous to amino acids 470 through 644 of E2 of HCV 1b.  
     
     
         41 . The peptide of  claim 35  comprising amino acids 644 through 661 of HCV 1 b E2.  
     
     
         42 . The peptide of  claim 35  comprising an amino acid sequence of E2 of an HCV, wherein the amino acids are analogous to amino acids 644 through 661 of E2 of HCV 1b.  
     
     
         43 . A peptide fragment of HCV E2 that contains a conformational epitope.  
     
     
         44 . The peptide wherein the peptide is at least 60% identical to a peptide of  claim 35 .  
     
     
         45 . The peptide wherein the peptide is at least 70% identical to a peptide of  claim 35 .  
     
     
         46 . The peptide wherein the peptide is at least 80% identical to a peptide of  claim 35 .  
     
     
         47 . The peptide wherein the peptide is at least 90% identical to a peptide of  claim 35 .  
     
     
         48 . (canceled)  
     
     
         49 . (canceled)  
     
     
         50 . An agent having sufficient three-dimensional structural similarity to an HCV E2 conformational epitope to compete for binding of the epitope to an antibody in the presence of the agent versus in the agent's absence, wherein the agent is a peptide.  
     
     
         51 .- 59 . (canceled)  
     
     
         60 . A vaccine comprising a peptide fragment of HCV E2 that contains a conformational epitope.  
     
     
         61 . The vaccine of  claim 60  comprising a peptide fragment of HCV E2 that contains an epitope recognized by the antibody directed to a conformational epitope of E2 protein of Hepatitis C virus.  
     
     
         62 . The vaccine of  claim 60  comprising a peptide fragment of HCV E2 that contains an epitope recognized by a human monoclonal antibody selected from the group consisting of CBH-2, CBH-4D, CBH-4B, CBH-4G, CBH-5, CBH-7, CBH-8C, CBH-8E, CBH-9, CBH-11, and CBH-17.  
     
     
         63 . The vaccine of  claim 60  comprising the peptide of  claim 35 .  
     
     
         64 . A vaccine comprising the agent of  claim 50 .  
     
     
         65 . The vaccine of  claim 60  further comprising an adjuvant.  
     
     
         66 - 74 . (canceled)