Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection

Humanized BALB/c mice (termed trimera mice) conditioned by lethal total bod y irradiation and bone marrow transplantation from SCID mice have been desc ribed to support rapid engraftment of human peripheral blood mononuclear ce lls (PBMC) and the induction of strong B and T cell responses after immuniz ation in vivo. Moreover, these mice can be infected with the hepatitis B an d C viruses (HBV, HCV). The current study employed this model to study ther apeutic vaccination approaches against the HBV. Thus, strong primary Th cel l responses against the HBV core (HBc) and the Borrelia burgdorferi control antigen were induced by transfer of antigen-loaded dendritic cells togethe r with autologous PBMC from HBV-naive donors as well as by vaccination with high doses of antigen or a DNA plasmid encoding for HBcAg. Moreover, prima ry peptide-specific CTL responses against the immunodominant epitope HBc(18 -27) were induced by HBc particle or DNA vaccination of chimera engrafted w ith HBV-naive PBMC. Finally, strong HBc-specific Th cell and antibody respo nses were induced by HBc or DNA vaccination of mice reconstituted with PBMC from a chronic HBV patient. Thus, since HBc represents the immunodominant antigen in self-limited HBV infection, HBc particles or DNA vectors are goo d candidates for therapeutic vaccination, that will be further studied in o ur model and clinical studies.