Effect of the hepatitis B virus SecdCD40L vaccine therapy in HBV transgenic mice: A vaccineinduced activation of antigen presenting dendritic cells

The classical hepatitis B virus (HBV) DNA vaccination plasmid only encodes for a single viral antigen, either the S or the PreS2/S antigen. Many strategies have been employed to improve the effect of these DNA vaccines. Our previous study identified that the fusion gene, HBV Secd cluster of differentiation 40 ligand (CD40L), may promote the activation of dendritic cells (DCs) and enhance their function in vitro. In the current study, the effect of HBV SecdCD40L vaccine therapy on liver DCs was investigated, and its therapeutic potential in HBV transgenic (HBVTg) mice was evaluated. The eukaryotic expression plasmid, pcDNA3.1SecdCD40L, was constructed by inserting the HBV S gene and mouse CD40L gene into the vector, pcDNA3.1 (+). HBVTg mice were immunized with pcDNA3.1SecdCD40L, pcDNA3.1S, pcDNA3.1 or PBS. Following this, immunophenotyping, cytokine production and Tcell activation were analyzed in the CD11cenriched DC population obtained from the liver. Vaccine efficacy was further assessed by the detection of serological and biochemical parameters. When comparing with other control groups, DCs from HBVTg mice immunized with pcDNA3.1SecdCD40L exhibited increased expression of immunologically important cell molecules (CD86 and major histocompatibility complex class II), proinflammatory cytokines (interleukin12), and enhanced capacity to promote allogeneic Tcell proliferation. Furthermore, the HBV SecdCD40L vaccine resulted in a significant inhibition of HBV DNA replication and downregulation of the hepatitis B virus surface antigen (HBsAg) in HBVTg mice, without obvious liver injury. In conclusion, the HBV SecdCD40L vaccine may be a feasible strategy for chronic HBV immunotherapy via promoting DC activation and function.