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Sci Transl Med. 2016 Dec 14;8(369):369ra179.

Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus.

Wang Q1,2, Yang H1,3, Liu X4, Dai L5, Ma T1,3, Qi J6, Wong G2,6,7, Peng R6, Liu S6,8, Li J1, Li S6, Song J6, Liu J9, He J10, Yuan H4, Xiong Y4, Liao Y11, Li J11, Yang J11, Tong Z1,2,6, Griffin BD12,13, Bi Y2,6,7, Liang M14, Xu X15, Qin C16, Cheng G9, Zhang X17,18, Wang P19, Qiu X12,13, Kobinger G12, Shi Y2,6, Yan J20,2,3,6,21, Gao GF22,5,6,7,8,14,23,24.

Author information

1
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
2
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
3
School of Life Sciences, Anhui University, Hefei 230039, China.
4
Jiangxi Province Center for Disease Control and Prevention, Nanchang 330029, China.
5
Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
6
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
7
CAS Center for Influenza Research and Early-warning, Chinese Academy of Sciences, Beijing 100101, China.
8
School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
9
Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
10
Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
11
Ganzhou Prefecture Center for Disease Control and Prevention, Ganzhou 331000, China.
12
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
13
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada.
14
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
15
MRC Human Immunology Unit, University of Oxford, Oxford OX3 9DS, U.K.
16
Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Institute of Medical Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, China.
17
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
18
Center for Biological Imaging, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
19
Faculty of Biological Science, University of Leeds, Leeds LS2 9JT, U.K.
20
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.
21
College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
22
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China. yanjh@im.ac.cn gaof@im.ac.cn.
23
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
24
Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.

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.

PMID:
27974667
DOI:
10.1126/scitranslmed.aai8336
[Indexed for MEDLINE]

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