title: An autophagosome-based therapeutic vaccine for HBV infection: a preclinical evaluation.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. xuemeng1800@sina.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. fanfei617@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. ccdl@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. jingyunini@126.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. sushussnine@gmail.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Su
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. ypfyinpengfei@foxmail.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. mcao1979@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China. mcao1979@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China. hhu@providence.org.|Laboratory of Cancer Immunobiology, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA. hhu@providence.org.
authors.forename: Hong-ming
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu, PR China. lxwang@seu.edu.cn.|Cancer Research and Biotherapy Center, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China. lxwang@seu.edu.cn.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001343:Autophagy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006509:Hepatitis B / Q000628:therapy*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000276:immunology*
chemical_list: D017325:Hepatitis B Vaccines