title: Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus.
abstract: The 2015-2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, Anhui University, Hefei 230039, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Yang
authors.affiliation: Jiangxi Province Center for Disease Control and Prevention, Nanchang 330029, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lianpan
authors.initials: L
authors.lastname: Dai
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, Anhui University, Hefei 230039, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Center for Influenza Research and Early-warning, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ruchao
authors.initials: R
authors.lastname: Peng
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Junfu
authors.initials: J
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: He
authors.affiliation: Jiangxi Province Center for Disease Control and Prevention, Nanchang 330029, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Jiangxi Province Center for Disease Control and Prevention, Nanchang 330029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Ganzhou Prefecture Center for Disease Control and Prevention, Ganzhou 331000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Ganzhou Prefecture Center for Disease Control and Prevention, Ganzhou 331000, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Ganzhou Prefecture Center for Disease Control and Prevention, Ganzhou 331000, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Griffin
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Center for Influenza Research and Early-warning, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: MRC Human Immunology Unit, University of Oxford, Oxford OX3 9DS, U.K.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|Center for Biological Imaging, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Faculty of Biological Science, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Peiyi
authors.initials: P
authors.lastname: Wang
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. yanjh@im.ac.cn gaof@im.ac.cn.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|School of Life Sciences, Anhui University, Hefei 230039, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. yanjh@im.ac.cn gaof@im.ac.cn.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|CAS Center for Influenza Research and Early-warning, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry*; D000914:Antibodies, Viral / Q000737:chemistry*; D001665:Binding Sites; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D003716:Dengue Virus; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011487:Protein Conformation; D014709:Vero Cells; D000071244:Zika Virus; D000071243:Zika Virus Infection / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes