Hepatitis b virus pre-s1 derived synthetic polypeptides and uses thereof

Abstract

This invention relates to a group of synthetic polypeptides, derived from the pre-S1 region of HBV, that efficiently interferes with early steps of an HBV infection. The peptides of the invention can be used in diagnostics for the detection of antigens and/or antibodies.

1 . An isolated synthetic polypeptide of the formula X-Y-Z (I) 
 wherein:    X is an amino radical, or an amino acid, for instance a methionine or absent;    Y is the amino acid sequence SEQ ID N o  2, or a N-terminally and/or C-terminally truncated form of this sequence, or variants thereof;    Z, linked to the —CO— group of the last residue of Y, is an amino group or an amino acid sequence comprising 1 to 30 consecutive amino acids from the pre-S1 region shown in SEQ ID N o  3 or absent;    said polypeptides being optionally chemically modified to bear a hydrophobic moiety.    
     
     
         2 . An isolated polypeptide according to  claim 1 , wherein the chemical modification consists in a myristoylation.  
     
     
         3 . An isolated polypeptide according to  claim 2 , wherein amino acid 1 of SEQ ID N o 2 is myristoylated.  
     
     
         4 . An isolated polypeptide according to  claim 1 ,  2  or  3 , comprising the entire amino acid sequence of SEQ ID N o 2.  
     
     
         5 . An isolated polypeptide according to any of  claims 1  to  4 , which amino acid sequence is SEQ ID N o 4.  
     
     
         6 . Method of in vitro inhibition of hepatocyte infection by HBV comprising using a polypeptide according to any of  claims 1  to  5 .  
     
     
         7 . Method of in vitro identification of a hepatocyte receptor involved in the attachment and/or penetration of HBV comprising using a polypeptide according to any of  claims 1  to  5 .  
     
     
         8 . Method for ex vivo diagnosis of HBV infection comprising using a polypeptide according to any of  claims 1  to  5 .  
     
     
         9 . Polypeptide according to any of  claims 1  to  5  as a drug.  
     
     
         10 . Pharmaceutical composition comprising, in a pharmaceutically acceptable carrier, a polypeptide according to one of the  claims 1  to  5 .  
     
     
         11 . Use of a polypeptide according to one of the  claims 1  to  5  for the manufacture of a medicament intended for the inhibition of in vivo HBV infection.  
     
     
         12 . Antibody directed against a polypeptide according to any of  claims 1  to  5 .  
     
     
         13 . Antibody according to  claim 12  as a drug.  
     
     
         14 . Method for assessing ex vivo the infectivity of HBV particles comprising using an antibody according to  claim 12 .  
     
     
         15 . Pharmaceutical composition comprising, in a pharmaceutically acceptable carrier, an antibody according to  claim 12 .  
     
     
         16 . Use of an antibody according to  claim 12  for the manufacture of a medicament intended for the in vivo inhibition of HBV infection.  
     
     
         17 . A vaccine composition comprising, in a pharmaceutically acceptable carrier, a polypeptide according to any one of  claims 1  to  5 .