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

Qihui Wang; Huabing Yang; Xiaoqing Liu; Lianpan Dai; Tong Ma; Jianxun Qi; Gary Wong; Ruchao Peng; Sheng Liu; Junfu Li; Shihua Li; Jian Song; Jianying Liu; Jianhua He; Hui Yuan; Ying Xiong; Yong Liao; Jianhua Li; Jianping Yang; Zhou Tong; Bryan D Griffin; Yuhai Bi; Mifang Liang; Xiaoning Xu; Chuan Qin; Gong Cheng; Xinzheng Zhang; Peiyi Wang; Xiangguo Qiu; Gary Kobinger; Yi Shi; Jinghua Yan; George F Gao

doi:10.1126/scitranslmed.aai8336

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

Sci Transl Med. 2016 Dec 14;8(369):369ra179. doi: 10.1126/scitranslmed.aai8336.

Authors

Qihui Wang^{1

2}, Huabing Yang^{1

3}, Xiaoqing Liu⁴, Lianpan Dai⁵, Tong Ma^{1

3}, Jianxun Qi⁶, Gary Wong^{2

6

7}, Ruchao Peng⁶, Sheng Liu^{6

8}, Junfu Li¹, Shihua Li⁶, Jian Song⁶, Jianying Liu⁹, Jianhua He¹⁰, Hui Yuan⁴, Ying Xiong⁴, Yong Liao¹¹, Jianhua Li¹¹, Jianping Yang¹¹, Zhou Tong^{1

2

6}, Bryan D Griffin^{12

13}, Yuhai Bi^{2

6

7}, Mifang Liang¹⁴, Xiaoning Xu¹⁵, Chuan Qin¹⁶, Gong Cheng⁹, Xinzheng Zhang^{17

18}, Peiyi Wang¹⁹, Xiangguo Qiu^{12

13}, Gary Kobinger¹², Yi Shi^{2

6}, Jinghua Yan^{20

2

3

6

21}, George F Gao^{22

5

6

7

8

14

23

24}

Affiliations

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.

PMID: 27974667
DOI: 10.1126/scitranslmed.aai8336

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.

MeSH terms

Animals
Antibodies, Monoclonal / chemistry
Antibodies, Neutralizing / chemistry*
Antibodies, Viral / chemistry*
Binding Sites
Chlorocebus aethiops
Cross Reactions
Dengue Virus
Disease Models, Animal
Epitopes / chemistry
Humans
Mice
Mice, Transgenic
Protein Conformation
Vero Cells
Zika Virus
Zika Virus Infection / immunology*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Epitopes

Grants and funding

CIHR/Canada