Therapeutic peptides based on HBcAg18-27 epitope can induce CTL response in vitro and in vivo

doi:10.3969/j.issn.1000-8861.2003.03.001

Abstract：Objective To design by computerized molecular design methods therapeutic polypeptides against chronic hepatitis B infection to explore how to trigger HLA-Ⅰ restricted HBV specific CD8+ T cell response and hence eradicate viruses within hepatocytes.Methods A new panel of polypeptides comprised of the immunodominant CTL and B- epitopes of HBV core antigen(HBcAg) and Pre-S2 protein, and the tetanus toxoid T helper epitope were synthesized, and their immunological properties were investigated in HLA-A2+ human peripheral blood mononuclear cells(PBMCs)and in Balb/c mice. Results The results demonstrated that polypeptides consist of the three kinds of epitopes could evoke in human PBMCs and in mice CD8+ CTL response. Palm-p44, a polypeptide which covalently linked palmitic acids to the carboxyl-termini of the potent HBcAg CTL epitope as built-in adjuvant induced vigorous CD8+ CTL response, no additional adjuvants were necessary in comparison to the free CTL epitope which failed to induce cell mediated immunity in mice. Conclusions The findings indicate that the lipidic built-in adjuvant can efficiently improve the immunogenicity of peptide antigens, and Palm-p44 might be a promising candidate for therapeutic peptide vaccines against chronic viral hepatitis B infection.