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

Abstract

Conformational epitopes of the envelope proteins E1 and 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 conserved conformational and linear epitopes of the HCV protein E1 or E2 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 E1 or E2 may be used to stratify patients based on their response to HCV and may be used to determine a proper treatment regimen. Pharmaceutical compositions for prevention and treatment of HCV, comprising one or more the monoclonal antibodies, are provided.

1 . A pharmaceutical composition for treating HCV infection comprising: 
 an antibody selected from the group consisting of CBH-2, CBH-5 and CBH-7; and;    a pharmaceutically acceptable carrier.    
     
     
         2 . A pharmaceutical composition for reducing the recurrence of HCV infection in a subject by passive immunotherapy comprising: 
 an antibody selected from the group consisting of CBH-2, CBH-5 and CBH-7; and    a pharmaceutically acceptable carrier.    
     
     
         3 . A pharmaceutical composition in accordance with  claim 2  wherein the subject is a liver transplant recipient.  
     
     
         4 . A pharmaceutical composition for preventing HCV infection in a subject comprising: 
 an antibody selected from the group consisting of CBH-2, CBH-5 and CBH-7; and a pharmaceutically acceptable carrier.    
     
     
         5 . A pharmaceutical composition in accordance with  claim 4  wherein the subject is a baby born to an HCV infected mother.  
     
     
         6 . A pharmaceutical composition in accordance with any of claims  1 - 5  combined with at least one other antiviral agent as an additional active ingredient.  
     
     
         7 . The method of  claim 6 , wherein said agent is selected from the group consisting of interferons, anti HCV monoclonal antibodies, anti HCV polyclonal antibodies, RNA polymerase inhibitors, ribavirin, protease inhibitors, IRES inhibitors, helicase inhibitors, antisense compounds, short interfering RNAs, short hairpin RNAs, and ribozymes.  
     
     
         8 . A pharmaceutical composition according to  claim 6  wherein the other antiviral agent is an anti HCV monoclonal antibody.  
     
     
         9 . A pharmaceutical composition for treating or preventing HCV infection comprising a fragment of an antibody selected from the group consisting of CBH-2, CBH-5, and CBH-7, wherein the fragment retains the antigen binding specificity of the whole antibody; and a pharmaceutically acceptable carrier.  
     
     
         10 . A method for the treatment of HCV infection comprising administering to an individual in need of treatment for HCV infection a therapeutically effective amount of a pharmaceutical composition according to  claim 1  to treat HCV infection.  
     
     
         11 . A method for reducing the recurrence of HCV infections in a subject by passive immunotherapy, comprising administering to the subject a pharmaceutical composition in accordance with  claim 2 .  
     
     
         12 . A method for treating a liver transplantation patient, comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition to reduce the likelihood of a recurrent HCV infection in said patient, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and, as an active ingredient, a human monoclonal antibody selected from the group consisting of: 
 (a) the monoclonal antibody CBH-2 which is secreted by the hybridoma cell line deposited in the ATCC under Accession no. PTA-4465;    (b) the monoclonal antibody CBH-5 which is secreted by the hybridoma cell line deposited in the ATCC under Accession no. PTA-4469;    (c) the monoclonal antibody CBH-7 which is secreted by the hybridoma cell line deposited in the ATCC under Accession no. PTA-4470; and    (d) fragments of the antibodies of (a)-(c) which retain the antigen binding characteristics of the whole antibody.    
     
     
         13 . A method according to  claim 10 , wherein the pharmaceutical composition further comprises at least one other active ingredient which is an antiviral agent.  
     
     
         14 . A method according to  claim 13 , wherein the antiviral agent is selected from the group consisting of interferons, anti HCV monoclonal antibodies, anti HCV polyclonal antibodies, RNA polymerase inhibitors, ribavirin, protease inhibitors, IRES inhibitors, helicase inhibitors, antisense compounds, short interfering RNAs, short hairpin RNAs, and ribozymes.  
     
     
         15 . A method for preventing HCV infections in a subject comprising administering to the subject a pharmaceutical composition in accordance with  claim 4 , to prevent HCV infections in the population.  
     
     
         16 . The method of  claim 15 , wherein the subject is a baby born to an HCV infected mother.