GB virus C (hepatitis G virus) for the treatment of HIV

Abstract

GB virus C (GBV-C or hepatitis G virus) is a flavivirus that frequently leads to chronic viremia in humans. The invention provides compositions and methods involving an anti-GBV-C antibody or other GBV-C binding agent, or a GBV-C antigen, for inhibiting and treating HIV infections.

1 . A therapeutic composition comprising a GBV-C peptide binding agent, wherein the composition attenuates HIV infectivity.  
     
     
         2 . The composition of  claim 1 , wherein the binding agent is an antibody.  
     
     
         3 . The composition of  claim 2 , wherein the antibody is a human antibody.  
     
     
         4 . The composition of  claim 2 , wherein the antibody is a monoclonal antibody.  
     
     
         5 . The composition of  claim 4 , wherein the antibody is a humanized antibody.  
     
     
         6 . The composition of  claim 1 , wherein the binding agent is an aptamer.  
     
     
         7 . The composition of  claim 1 , wherein the GBV-C peptide is derived from a GBV-C envelope protein.  
     
     
         8 . The composition of  claim 7 , wherein the GBV-C envelope protein is a E2 protein.  
     
     
         9 . A method for preventing or treating HIV infection comprising administering to a subject a composition comprising a GBV-C peptide binding agent, wherein the binding agent attenuates HIV infectivity.  
     
     
         10 . The method of  claim 9 , wherein the binding agent is an anti-GBV-C E2 antibody.  
     
     
         11 . The method of  claim 10 , wherein the antibody is a human antibody  
     
     
         12 . The method of  claim 10 , wherein the antibody is a monoclonal antibody.  
     
     
         13 . The method of  claim 12 , wherein the antibody is a humanized antibody.  
     
     
         14 . The method of  claim 9 , wherein the binding agent is an aptamer.  
     
     
         15 . The method of  claim 9 , further comprising administration of at least a second anti-HIV therapy.  
     
     
         16 . The method of  claim 15 , wherein the second anti-HIV therapy is administration of an infectious GBV-C virus.  
     
     
         17 . The method of  claim 16 , wherein the GBV-C virus is administered before the therapeutic composition.  
     
     
         18 . The method of  claim 15 , wherein the second anti-HIV therapy is HAART therapy.  
     
     
         19 . The method of  claim 15 , wherein the second anti-HIV therapy is AZT therapy.  
     
     
         20 . The method of  claim 9 , wherein the therapeutic composition is administered at least twice.  
     
     
         21 . A method of preparing an antibody comprising immunizing a non-human animal with a GBV-C E2 protein or fragment thereof.  
     
     
         22 . A method of preparing a therapeutic composition comprising: 
 a) contacting a cell with a polynucleotide encoding a HIV attenuating GBV-C peptide binding agent under conditions effective to allow expression of all or part of a GBV-C peptide binding agent;    b) collecting the expressed GBV-C peptide binding agent; and    c) constituting the GBV-C peptide binding agent in a pharmaceutically acceptable solution.    
     
     
         23 . The method of  claim 22 , wherein the GBV-C peptide binding agent is an antibody.  
     
     
         24 . The method of  claim 23 , wherein the antibody is a human antibody.  
     
     
         25 . The method of  claim 23 , wherein the anibody is a monoclonal antibody.  
     
     
         26 . The method of  claim 25 , wherein the antibody is a humanized antibody.  
     
     
         27 . The composition of  claim 22 , wherein the binding agent is an aptamer.  
     
     
         28 . A vaccine comprising an antigen derived from a GBV-C polypeptide.  
     
     
         29 . The vaccine of  claim 28 , wherein the antigen is all or part of a GBV-C E2 polypeptide.  
     
     
         30 . The vaccine of  claim 29 , wherein the antigen is a GBV-C E2-derived peptide.  
     
     
         31 . The vaccine of  claim 30 , wherein the peptide has an amino acid sequence comprising FYEPLVRRC (SEQ ID NO: 8).  
     
     
         32 . The vaccine of  claim 31 , wherein the peptide has an amino acid sequence comprising LTGGFYEPLVRRC (SEQ ID NO:6).  
     
     
         33 . The vaccine of  claim 32 , wherein the peptide has an amino acid sequence comprising GGAGLTGGFYEPLVRRC (SEQ ID NO:7).  
     
     
         34 . A method of immunizing a subject comprising contacting said subject with a composition comprising a GBV-C polypeptide or fragment thereof.  
     
     
         35 . The method of  claim 35 , wherein said composition further comprises an adjuvant.  
     
     
         36 . The method of  claim 35 , wherein said GBV-C polypeptide is an E2 polypeptide.  
     
     
         37 . The method of  claim 36 , wherein the E2-polypeptide is an E2 peptide.  
     
     
         38 . The method of  claim 37 , wherein the E2 peptide has an amino acid sequence comprising FYEPLVRRC (SEQ ID NO:8).  
     
     
         39 . The method of  claim 38 , wherein the E2 peptide has an amino acid sequence comprising LTGGFYEPLVRRC (SEQ ID NO:6).  
     
     
         40 . The method of  claim 39 , wherein the E2 peptide has an amino acid sequence comprising GGAGLTGGFYEPLVRRC (SEQ ID NO:7).