Effect of the hepatitis B virus S-ecdCD40L vaccine therapy in HBV transgenic mice: A vaccine-induced activation of antigen presenting dendritic cells

Abstract

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 S-ecd 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 S-ecdCD40L vaccine therapy on liver DCs was investigated, and its therapeutic potential in HBV transgenic (HBV-Tg) mice was evaluated. The eukaryotic expression plasmid, pcDNA3.1-S-ecdCD40L, was constructed by inserting the HBV S gene and mouse CD40L gene into the vector, pcDNA3.1 (+). HBV-Tg mice were immunized with pcDNA3.1-S-ecdCD40L, pcDNA3.1-S, pcDNA3.1 or PBS. Following this, immunophenotyping, cytokine production and T-cell activation were analyzed in the CD11c-enriched 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 HBV-Tg mice immunized with pcDNA3.1-S-ecdCD40L exhibited increased expression of immunologically important cell molecules (CD86 and major histocompatibility complex class II), pro-inflammatory cytokines (interleukin-12), and enhanced capacity to promote allogeneic T-cell proliferation. Furthermore, the HBV S-ecdCD40L vaccine resulted in a significant inhibition of HBV DNA replication and downregulation of the hepatitis B virus surface antigen (HBsAg) in HBV-Tg mice, without obvious liver injury. In conclusion, the HBV S-ecdCD40L vaccine may be a feasible strategy for chronic HBV immunotherapy via promoting DC activation and function.