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

Journal of Translational Medicine

Lixin Wang¹  Hong-ming Hu²  Wei Zhao¹  Meng Cao³  Pengfei Yin³  Shu Su³  Jingyu Liu³  Lei Ding³  Fei Fan³  Meng Xue³ 

[1] Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China;Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA;Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China

关键词: Autophagy;    Therapeutic vaccine;    DRibbles;    Hepatitis B virus;   

Others  :  1146398
DOI  :  10.1186/s12967-014-0361-4

 received in 2014-08-05, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

For 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.

Methods

We 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 mimic acute and chronic HBV infection in human.

Results

When 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-γ producing T cells in the chronic mouse model.

Conclusions

These 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.

【 授权许可】

   
2014 Xue et al.; licensee BioMed Central.

【 图 表 】

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