Recombinant hepatitis B core antigen carrying preS1 epitopes induce immune response against chronic HBV infection

Many studies have provided evidence that core antigen of hepatitis B virus (HBcAg) is extremely immunogenic, HBcAg can be function as both a T-cell-dependent antigen and a T-cell-independent antigen, and thus may be a promising candidate for therapeutic vaccine for control of chronic HBV infection. HBcAg is also an effective carrier for heterologous peptide epitopes. The preS1 is a surface protein of HBV and is immunogenic at the T and B cell level. The amino acid sequence 21-47 of preS1 is crucial for HBV binding to human hepatocytes as well as to PBMC and haematopoietic cell lines of the B cell lineage. Here we expressed a chimeric protein named HBVCS1, created by fusing the preS1 sequence 3-55 to the carboxyl terminus of the truncated HBcAg sequence 1-155 in E. coli. Analysis of its antigenicity and immunogenicity revealed that both HBc and preS I epitopes are surface accessible, and that fusion of preS 1 did not affect the HBc antigenicity and immunogenicity of the truncated HBc sequence. HBVCS1 induced strong anti-HBc and moderate anti-preS1 immune responses as well specific T-cell response in Balb/c mice. HBVCS1 vaccination reduced of the titer of HBsAg and HBV DNA in sera of HBV-Tg mice. These results indicate that HBVCS1 may have potential as a therapeutic vaccine for treatment of HBV chronic infection. (C) 2003 Elsevier Ltd. All rights reserved.