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An Autophagosome-Based Therapeutic Vaccine for Hbv Infection: A Preclinical Evaluation
SUNLONG BIOTECH / 2024-01-09
  • Author:Xue, M., Fan, F., Ding, L., Liu, J., Su, S., Yin, P., Cao, M., Zhao, W., Hu, H. M. & Wang, L.

  • Periodical:Journal of translational medicine 12, 361 (2014)

  • Article source

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.

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