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  4. A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice
 
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A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice

Journal
Gut
Journal Volume
69
Journal Issue
2
Pages
343-354
Date Issued
2020
Author(s)
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.
DOI
10.1136/gutjnl-2018-317725
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
Abstract
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).
Subjects
drug development; hepatitis B; immunotherapy
SDGs

[SDGs]SDG3

Other Subjects
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
Publisher
BMJ Publishing Group
Type
journal article

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