Zhang T.-Y.Guo X.-R.Wu Y.-T.Kang X.-Z.Zheng Q.-B.Qi R.-Y.Chen B.-B.Lan Y.Wei M.Wang S.-J.Xiong H.-L.Cao J.-L.Zhang B.-H.Qiao X.-Y.Huang X.-F.Wang Y.-B.Fang M.-J.Zhang Y.-L.Cheng T.Chen Y.-X.Zhao Q.-J.Li S.-W.Ge S.-X.PEI-JER CHENZhang J.Yuan Q.Xia N.-S.2021-07-032021-07-0320200017-5749https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063731654&doi=10.1136%2fgutjnl-2018-317725&partnerID=40&md5=977cb5751e303be157e75d3aee7559edhttps://scholars.lib.ntu.edu.tw/handle/123456789/568309Objective This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. Methods A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. Results Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. Conclusions The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans. ? 2020 Author(s).drug development; hepatitis B; immunotherapy[SDGs]SDG3drug carrier; epitope; hepatitis B core antigen; hepatitis B surface antibody; hepatitis B surface antigen; hepatitis B vaccine; immunoglobulin G; virus DNA; antivirus agent; epitope; hepatitis B antibody; hepatitis B surface antigen; hepatitis B vaccine; immunological adjuvant; virus DNA; amino acid sequence; animal experiment; animal model; animal tissue; antibody response; Article; B lymphocyte; bat; chronic hepatitis B; controlled study; dose response; drug design; drug efficacy; drug formulation; drug safety; female; Hepatitis B virus; humoral immunity; hydrodynamics; in vitro study; Macaca fascicularis; male; mouse; New Zealand White (rabbit); nonhuman; priority journal; roundleaf bat; transgenic mouse; vaccination; vaccine immunogenicity; viral clearance; virostatic activity; virus carrier; virus like agent; virus load; animal; Bagg albino mouse; biosynthesis; blood; chronic hepatitis B; genetics; immunology; immunotherapy; Leporidae; multimodality cancer therapy; procedures; virology; Adjuvants, Immunologic; Animals; Antiviral Agents; Combined Modality Therapy; DNA, Viral; Dose-Response Relationship, Immunologic; Epitopes, B-Lymphocyte; Female; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B virus; Hepatitis B, Chronic; Immunity, Humoral; Immunotherapy; Macaca fascicularis; Male; Mice, Inbred BALB C; Mice, Transgenic; Rabbitsjournal article10.1136/gutjnl-2018-317725309266532-s2.0-85063731654