Abstract
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 mimic 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-γ 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0361-4) contains supplementary material, which is available to authorized users.
Highlights
For more than 240 million chronic hepatitis B virus (HBV) carriers worldwide, effective therapeutic HBV vaccines are urgently needed
We examined whether different autophagy inducers could increase the production of DRibbles from a HBV-producing hepatoma cells and further investigated whether HBV+ DRibbles vaccine could induce polyvalent anti-HBV immune responses and reduce ‘HBV infection’ in a mouse model [18]
DRibbles are capable to encapsulate multiple HBV antigens First, we investigated whether DRibbles contained HBV antigens when they were prepared from HepG2.2.15 cells that were transfected with HBV DNA and stably expressed HBV antigens
Summary
For more than 240 million chronic HBV carriers worldwide, effective therapeutic HBV vaccines are urgently needed. A vaccination strategy using DNA prime and protein boost worked poorly in a recent randomized clinical trial [8] These rather disappointing results are likely related to the fact that vaccination with the HBsAg alone is insufficient and a strong, polyvalent, and poly-functional CD8+ T-cell response against other HBV antigen besides HBsAg is required for viral clearance. Such a T-cell response was detected in subjects with self-limited HBV infection, but it is exhausted and
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