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Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

Bin Ju, Qi Zhang, Xiangyang Ge, Ruoke Wang, Jiazhen Yu, Sisi Shan, Bing Zhou, Shuo Song, Xian Tang, Jinfang Yu, Jiwan Ge, Jun Lan, Jing Yuan, Haiyan Wang, Juanjuan Zhao, Shuye Zhang, Youchun Wang, Xuanling Shi, Lei Liu, Xinquan Wang, Zheng Zhang, View ORCID ProfileLinqi Zhang
doi: https://doi.org/10.1101/2020.03.21.990770
Bin Ju
1 Shenzhen Third People Hospital, China;
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  • For correspondence: jubin2013@163.com
Qi Zhang
2 Tsinghua University, Beijing, China;
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  • For correspondence: zhangqi2013@mail.tsinghua.edu.cn
Xiangyang Ge
3 Shenzhen Third People's Hospital, China;
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Ruoke Wang
4 Tsinghua University, China;
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Jiazhen Yu
3 Shenzhen Third People's Hospital, China;
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Sisi Shan
4 Tsinghua University, China;
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  • For correspondence: sss15@mails.tsinghua.edu.cn
Bing Zhou
3 Shenzhen Third People's Hospital, China;
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  • For correspondence: zhoubing9169@163.com
Shuo Song
5 Shenzhen Third People's Hospital;
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Xian Tang
3 Shenzhen Third People's Hospital, China;
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Jinfang Yu
4 Tsinghua University, China;
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Jiwan Ge
4 Tsinghua University, China;
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Jun Lan
4 Tsinghua University, China;
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  • For correspondence: lanj17@mails.tsinghua.edu.cn
Jing Yuan
3 Shenzhen Third People's Hospital, China;
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Haiyan Wang
5 Shenzhen Third People's Hospital;
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Juanjuan Zhao
3 Shenzhen Third People's Hospital, China;
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  • For correspondence: zhaojuanjuan1225@gmail.com
Shuye Zhang
6 Fudan University, China;
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  • For correspondence: zhangshuye@shphc.org.cn
Youchun Wang
7 National Institutes for Food and Drug Control, Beijing, China.;
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  • For correspondence: wangyc@nifdc.org.cn
Xuanling Shi
8 Tsinghua University School of Medicine;
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  • For correspondence: shixuanlingsk@mail.tsinghua.edu.cn
Lei Liu
3 Shenzhen Third People's Hospital, China;
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Xinquan Wang
9 Tsinghua University
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  • For correspondence: xinquanwang@mail.tsinghua.edu.cn
Zheng Zhang
3 Shenzhen Third People's Hospital, China;
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  • For correspondence: zhangzheng1975@aliyun.com
Linqi Zhang
9 Tsinghua University
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  • ORCID record for Linqi Zhang
  • For correspondence: zhanglinqi@tsinghua.edu.cn
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Abstract

The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. SARS CoV-2 cellular entry depends on binding between the viral Spike protein receptor-binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) target cell receptor. Here, we report on the isolation and characterization of 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells of eight SARS-CoV-2 infected individuals. These mAbs come from diverse families of antibody heavy and light chains without apparent enrichment for particular families in the repertoire. In samples from one patient selected for further analyses, we found coexistence of germline and germline divergent clones. Both clone types demonstrated impressive binding and neutralizing activity against pseudovirus and live SARS-CoV-2. However, the antibody neutralizing potency is determined by competition with ACE2 receptor for RBD binding. Surprisingly, none of the SARS CoV 2 antibodies nor the infected plasma cross-reacted with RBDs from either SARS CoV or MERS CoV although substantial plasma cross reactivity to the trimeric Spike proteins from SARS-CoV and MERS-CoV was found. These results suggest that antibody response to RBDs is viral species-specific while that cross-recognition target regions outside the RBD. The specificity and neutralizing characteristics of this plasma cross-reactivity requires further investigation. Nevertheless, the diverse and potent neutralizing antibodies identified here are promising candidates for prophylactic and therapeutic SARS-CoV-2 interventions.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 25, 2020.
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Potent human neutralizing antibodies elicited by SARS-CoV-2 infection
Bin Ju, Qi Zhang, Xiangyang Ge, Ruoke Wang, Jiazhen Yu, Sisi Shan, Bing Zhou, Shuo Song, Xian Tang, Jinfang Yu, Jiwan Ge, Jun Lan, Jing Yuan, Haiyan Wang, Juanjuan Zhao, Shuye Zhang, Youchun Wang, Xuanling Shi, Lei Liu, Xinquan Wang, Zheng Zhang, Linqi Zhang
bioRxiv 2020.03.21.990770; doi: https://doi.org/10.1101/2020.03.21.990770
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Potent human neutralizing antibodies elicited by SARS-CoV-2 infection
Bin Ju, Qi Zhang, Xiangyang Ge, Ruoke Wang, Jiazhen Yu, Sisi Shan, Bing Zhou, Shuo Song, Xian Tang, Jinfang Yu, Jiwan Ge, Jun Lan, Jing Yuan, Haiyan Wang, Juanjuan Zhao, Shuye Zhang, Youchun Wang, Xuanling Shi, Lei Liu, Xinquan Wang, Zheng Zhang, Linqi Zhang
bioRxiv 2020.03.21.990770; doi: https://doi.org/10.1101/2020.03.21.990770

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