Immune tolerance against HBV can be overcome in HBV transgenic mice by immunization with Dendritic Cells pulsed by HBVsvp

Introduction: It is known that in chronic Hepatitis B Virus (HBV) carriers the function of dendritic cells (DC) as well as the function of T-cells and B-cells is impaired. Within HBV transgenic mice no immune response against HBV is found due to central and peripheral tolerance. We recently showed that it is possible to activate DC of mice in vitro by pulsation with HBV sub viral particles (HBVsvp) and that by immunizing mice with such activated DC specific anti HBV directed immune responses are induced on cellular and humoral level. Aim of the study: In the present study we used HBV transgenic mice to observe immune responses in a model for chronic HBV infection. HBVsvp, together with LPS as a co-activating molecule, were used for in vitro activation of DC. HBV transgenic mice were injected by such pulsed DC two times. Four weeks after DC vaccination humoral and cellular immune responses, HBe antigen levels and histology were analyzed. Results: A strong HBV specific T-cell response was found in DC vaccinated HBV-transgenic mice. In addition, high antibody levels against HBc and HBs were detected. These results demonstrate that in vitro activation of DC and HBVsvp loading can overcome the tolerance against HBV and reactivate B- and T-cell function in HBV transgenic mice. Conclusion: In chronic HBV carriers impaired DC, as key players of cellular and humoral immunity, may be reactivated in vitro and could help patients to clear the infection.

Dendritic cells - HBV - Hepatitis B - subviral particle