Experimental evidence suggests that
hepatitis B core antigen (
HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with
chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with
hepatitis B surface antigen (
HBsAg)-based prophylactic
vaccines with unsatisfactory clinical outcomes. In this study, we prepared
HBsAg-pulsed dendritic cells (DC) and
HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these
antigens, which may serve as a better
therapy for CHB. The kinetics of
HBsAg, antibody levels against
HBsAg (anti-HBs), proliferation of
HBsAg- and
HBcAg-specific lymphocytes, production of
antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either
HBsAg- or
HBcAg-pulsed DC. Vaccination with
HBsAg-pulsed DC induced
HBsAg-specific immunity, but failed to induce
HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with
HBcAg-pulsed DC resulted in: (1)
HBsAg negativity, (2) production of anti-HBs, and (3) development of
HBsAg- and
HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with
HBcAg-pulsed DC compared to
HBsAg-pulsed DC (p<0.05). The capacity of
HBcAg to modulate both
HBsAg- and
HBcAg-specific immunity in HBV TM, and activation of endogenous DC in HBV TM without inducing liver damage suggests that
HBcAg should be an integral component of the therapeutic
vaccine against CHB.