title: Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen.
abstract: OBJECTIVE
  This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models.
  
  
  METHODS
  Therapeutic effects of mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated.
  
  
  RESULTS
  Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fcγ receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody-viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance.
  
  
  CONCLUSIONS
  These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Tian-Ying
authors.initials: TY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China Xiamen Blood Services, Xiamen 361002, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Lun-Zhi
authors.initials: LZ
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lo
authors.affiliation: Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan.
authors.forename: Cheng-Pu
authors.initials: CP
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chang-Ru
authors.initials: CR
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Xue-Ran
authors.initials: XR
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biological Sciences and Center for Bioimaging Sciences, National University of Singapore, Singapore, 117543, Singapore National University of Singapore (Suzhou) Research Institute, Suzhou 215123, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Mo
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Wen-Xin
authors.initials: WX
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Academia Sinica, Institute of Biomedical Sciences, Taipei, Taiwan.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: James Wk
authors.initials: JW
authors.lastname: Shih
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Qin-Jian
authors.initials: QJ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China Department of Biological Sciences and Center for Bioimaging Sciences, National University of Singapore, Singapore, 117543, Singapore National University of Singapore (Suzhou) Research Institute, Suzhou 215123, China.
authors.forename: Y Adam
authors.initials: YA
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Science & School of Public Health, Xiamen University, Xiamen, China National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science & School of Public Health, Xiamen University, Xiamen, China.
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004279:DNA, Viral / Q000187:drug effects; D004195:Disease Models, Animal; D000939:Epitopes; D006514:Hepatitis B Surface Antigens / Q000187:drug effects* / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D022781:Hepatocytes / Q000821:virology; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D000939:Epitopes; D006514:Hepatitis B Surface Antigens
keywords: ANTIBODY TARGETED THERAPY; ANTIVIRAL THERAPY; HEPATITIS B; IMMUNOTHERAPY; INFECTIOUS DISEASE