PT - JOURNAL ARTICLE AU - Huajun Zhao AU - Yating Yu AU - Zhenguang Liu AU - Lulu Huang AU - Ailu Yang AU - Lina Jiao AU - Zuchen Song AU - Yucan Wang AU - Cuiping Bao AU - Ruihong Yu AU - Lin Yu AU - Guan Wang AU - Deyi Wang AU - Qiuju Han AU - Liang Zhang AU - Liang Huang AU - Jian Zhang AU - Yong Yang AU - Ang Lin TI - An HBV mRNA vaccine with favorable virological suppression and superior immunity AID - 10.1101/2022.11.18.517095 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.11.18.517095 4099 - http://biorxiv.org/content/early/2022/11/20/2022.11.18.517095.short 4100 - http://biorxiv.org/content/early/2022/11/20/2022.11.18.517095.full AB - Clinical 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.Competing Interest StatementThe authors have declared no competing interest.