https://scholars.lib.ntu.edu.tw/handle/123456789/568309
標題: | A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice | 作者: | 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 CHEN Zhang J. Yuan Q. Xia N.-S. |
關鍵字: | drug development; hepatitis B; immunotherapy | 公開日期: | 2020 | 出版社: | BMJ Publishing Group | 卷: | 69 | 期: | 2 | 起(迄)頁: | 343-354 | 來源出版物: | Gut | 摘要: | Objective 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). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063731654&doi=10.1136%2fgutjnl-2018-317725&partnerID=40&md5=977cb5751e303be157e75d3aee7559ed https://scholars.lib.ntu.edu.tw/handle/123456789/568309 |
ISSN: | 0017-5749 | DOI: | 10.1136/gutjnl-2018-317725 | SDG/關鍵字: | drug 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; Rabbits |
顯示於: | 臨床醫學研究所 |
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