An autophagosome-based therapeutic vaccine for HBV infection: a preclinical evaluation

Meng Xue, Fei Fan, Lei Ding, Jingyu Liu, Shu Su, Pengfei Yin, Meng Cao, Wei Zhao, Hong-ming Hu, Lixin Wang

BackgroundFor more than 240 million chronic HBV carriers worldwide, effective therapeutic HBV vaccines are urgently needed. Recently, we demonstrated that autophagosomes were efficient antigens carriers and capable to cross-prime robust T-cell responses and mediate regression of multiple established tumors. Here we tested whether autophagosomes derived from HBV expressing cells could also function as a therapeutic vaccine.MethodsWe generated an autophagosome-based HBV vaccine from HBV-expressing hepatoma cells and examined its ability to induce polyvalent anti-HBV T-cell responses and therapeutic efficacy in mouse models that mimics acute and chronic HBV infection in human.ResultsWhen compared to the vaccine based on recombinant HBsAg, autophagosome-based HBV vaccine cross-primed multi-specific anti-HBV T-cell responses and significantly reduced HBV replication and HBcAg expression in livers of both acute and chronic mouse models. Therapeutic effect of this HBV vaccine depended on anti-HBV CD8+ effector T cells and associated with increased HBsAg and HBcAg specific IFN-¿ producing T cells in the chronic mouse model.ConclusionsThese results indicated that autophagosome-based HBV vaccine could effectively suppress the HBV replication, clear the HBV infected hepatocytes, and break the HBV tolerance in mouse model. The potential clinical application of autophagosome-based HBV vaccine is discussed.