An HBV mRNA vaccine with favorable virological suppression and superior immunity

Abstract

AbstractClinical management of chronic hepatitis B (CHB) virus infection remains a big challenge and urges the development of novel therapeutics to achieve long-term virological control and seroconversion. In this study, we report on the development and evaluation of a highly efficacious therapeutic mRNA vaccine encoding the full-length hepatitis B virus (HBV) surface antigen (HBsAg). In pAAV-HBV1.2 and rAAV8-HBV1.3-transduced CHB mouse models, the HBV mRNA vaccine demonstrated potent therapeutic efficacy indicated by a complete serum viral clearance, a remarkable decline in intrahepatic HBcAg, viral DNA and RNA copies, as well as the induction of robust levels of anti-HBs antibodies, virus-specific T cells and memory B cells. In addition, the HBV mRNA vaccine induced strong innate immune activation, represented by the maturation of CD8α+and CD103+cDC1, CD11b+cDC2, monocytes and neutrophils. Taken together, the HBV mRNA vaccine is a promising therapeutic candidate holding prospect for further development and clinical investigation.