Hepatitis B virus treatment

Abstract

The invention relates to HBV antigen-containing compositions that are useful in treating or preventing HBV infection. The content of the compositions can vary, as described herein, but the compositions comprise a stress protein, or a portion (e.g., a fragment) or derivative thereof, and an HBV antigen.

1 . An isolated fusion protein comprising a stress protein or a portion thereof and a hepatitis B virus (HBV) core antigen, wherein the fusion protein, when administered to an individual, induces or enhances an immune response against the HBV core antigen.  
     
     
         2 . The fusion protein in  claim 1 , wherein the stress protein is a heat shock protein.  
     
     
         3 . The fusion protein of  claim 1 , wherein the stress protein is selected from the Hsp10, Hsp40, Hsp60, Hsp70, Hsp90, Hsp100-200, Hsp100, Lon, TF55, Hsp40, FKBPs, cyclophilin, Hsp20-30, ClpP, GrpE, ubiquitin, calnexin, or protein disulfide isomerase or small molecular weight family of stress proteins.  
     
     
         4 . The fusion protein of  claim 3 , wherein the stress protein is  M. bovis  BCG hsp65.  
     
     
         5 . The fusion protein of  claim 1 , wherein the HBV core antigen comprises a fragment of the HBV core antigen lacking all or part of the C-terminal arginine-rich domain.  
     
     
         6 . The fusion protein of  claim 5 , wherein the HBV core antigen fragment comprises amino acid 1 to 149 or amino acid 1 to 151 of the core antigen of the HBV adw strain.  
     
     
         7 . A fusion protein comprising the sequence shown in any one of  FIGS. 6, 8 ,  10  or  12 .  
     
     
         8 . A pharmaceutical composition comprising the fusion protein of  claim 1 .  
     
     
         9 . The pharmaceutical composition of  claim 8 , further comprising a pharmaceutically acceptable carrier or excipient.  
     
     
         10 . An isolated nucleic acid comprising a sequence that encodes the fusion protein of  claim 1 .  
     
     
         11 . An isolated nucleic acid comprising a sequence shown in any one of  FIGS. 5, 7 ,  9  or  11 .  
     
     
         12 . An expression vector comprising the nucleic acid of  claim 10 .  
     
     
         13 . A retroviral vector comprising the nucleic acid of  claim 10 .  
     
     
         14 . A cell comprising the expression vector of  claim 12 .  
     
     
         15 . A method of making a fusion protein according to  claim 1 , the method comprising: 
 (a) providing the cell of  claim 14 , and    (b) culturing the cell under conditions that permit expression of the nucleic acid.    
     
     
         16 . A method of inducing or enhancing an immune response against an HBV core antigen in a subject, the method comprising administering to the subject an effective amount of the fusion protein of  claim 1 .  
     
     
         17 . A method of inducing or enhancing an immune response against an HBV core antigen in a subject, the method comprising administering to the subject an effective amount of the pharmaceutical composition of  claim 8 .  
     
     
         18 . The method of  claim 17 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.  
     
     
         19 . A method of inducing or enhancing an immune response against an HBV core antigen, the method comprising administering to a subject an effective amount of the expression vector of  claim 12 .  
     
     
         20 . A method of inducing or enhancing an immune response against an HBV core antigen, the method comprising administering to a subject an effective amount of the expression vector of  claim 13.