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Human neutralizing antibodies elicited by SARS-CoV-2 infection

Author

Listed:
  • Bin Ju

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Qi Zhang

    (Tsinghua University)

  • Jiwan Ge

    (Tsinghua University)

  • Ruoke Wang

    (Tsinghua University)

  • Jing Sun

    (State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University)

  • Xiangyang Ge

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Jiazhen Yu

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Sisi Shan

    (Tsinghua University)

  • Bing Zhou

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Shuo Song

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Xian Tang

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Jinfang Yu

    (Tsinghua University)

  • Jun Lan

    (Tsinghua University)

  • Jing Yuan

    (Shenzhen Third People’s Hospital)

  • Haiyan Wang

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital)

  • Juanjuan Zhao

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Shuye Zhang

    (Fudan University)

  • Youchun Wang

    (Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control)

  • Xuanling Shi

    (Tsinghua University)

  • Lei Liu

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Jincun Zhao

    (State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University)

  • Xinquan Wang

    (Tsinghua University)

  • Zheng Zhang

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Linqi Zhang

    (Tsinghua University)

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention1–3. The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2)2,4–6. Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2.

Suggested Citation

  • Bin Ju & Qi Zhang & Jiwan Ge & Ruoke Wang & Jing Sun & Xiangyang Ge & Jiazhen Yu & Sisi Shan & Bing Zhou & Shuo Song & Xian Tang & Jinfang Yu & Jun Lan & Jing Yuan & Haiyan Wang & Juanjuan Zhao & Shuy, 2020. "Human neutralizing antibodies elicited by SARS-CoV-2 infection," Nature, Nature, vol. 584(7819), pages 115-119, August.
  • Handle: RePEc:nat:nature:v:584:y:2020:i:7819:d:10.1038_s41586-020-2380-z
    DOI: 10.1038/s41586-020-2380-z
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    Citations

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    Cited by:

    1. Oscar Guzmán-Martínez & Kathia Guardado & Miguel Varela-Cardoso & Alejandro Trujillo-Rivera & Iván Gómez-Ñañez & María Cristina Ortiz-León & Rafaela Espinosa & Celso Ramos & Julio Isael Pérez-Carreón , 2021. "Potential Protection of Pre-Existent Antibodies to Human Coronavirus 229E on COVID-19 Severity," IJERPH, MDPI, vol. 18(17), pages 1-9, August.
    2. Caitlin I. Stoddard & Kevin Sung & Zak A. Yaffe & Haidyn Weight & Guillaume Beaudoin-Bussières & Jared Galloway & Soren Gantt & Judith Adhiambo & Emily R. Begnel & Ednah Ojee & Jennifer Slyker & Dalto, 2023. "Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Tomohiro Takano & Takashi Sato & Ryutaro Kotaki & Saya Moriyama & Shuetsu Fukushi & Masahiro Shinoda & Kiyomi Kabasawa & Nagashige Shimada & Mio Kousaka & Yu Adachi & Taishi Onodera & Kazutaka Terahar, 2023. "Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Bin Ju & Qing Fan & Miao Wang & Xuejiao Liao & Huimin Guo & Haiyan Wang & Xiangyang Ge & Lei Liu & Zheng Zhang, 2022. "Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections," Nature Communications, Nature, vol. 13(1), pages 1-6, December.
    5. Danique M. H. Rijswijck & Albert Bondt & Max Hoek & Karlijn Straten & Tom G. Caniels & Meliawati Poniman & Dirk Eggink & Chantal Reusken & Godelieve J. Bree & Rogier W. Sanders & Marit J. Gils & Alber, 2022. "Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Yifan Wang & Caixuan Liu & Chao Zhang & Yanxing Wang & Qin Hong & Shiqi Xu & Zuyang Li & Yong Yang & Zhong Huang & Yao Cong, 2022. "Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Mendoza, Daniel E. & Ochoa-Sánchez, Ana & Samaniego, Esteban P., 2022. "Forecasting of a complex phenomenon using stochastic data-based techniques under non-conventional schemes: The SARS-CoV-2 virus spread case," Chaos, Solitons & Fractals, Elsevier, vol. 158(C).
    8. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Yanqun Wang & An Yan & Deyong Song & Maoqin Duan & Chuangchuang Dong & Jiantao Chen & Zihe Jiang & Yuanzhu Gao & Muding Rao & Jianxia Feng & Zhaoyong Zhang & Ruxi Qi & Xiaomin Ma & Hong Liu & Beibei Y, 2024. "Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Andrew C. Hunt & Bastian Vögeli & Ahmed O. Hassan & Laura Guerrero & Weston Kightlinger & Danielle J. Yoesep & Antje Krüger & Madison DeWinter & Michael S. Diamond & Ashty S. Karim & Michael C. Jewett, 2023. "A rapid cell-free expression and screening platform for antibody discovery," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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