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Human neutralizing antibodies elicited by SARS-CoV-2 infection.
Nature. 2020 08; 584(7819):115-119.Nat

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.

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Authors+Show Affiliations

Ju B
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Zhang Q
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, China.
Ge J
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.
Wang R
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, China.
Sun J
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, Guangzhou, China.
Ge X
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Yu J
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Shan S
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, China.
Zhou B
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Song S
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Tang X
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Yu J
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.
Lan J
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.
Yuan J
Department for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.
Wang H
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.
Zhao J
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Zhang S
Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Wang Y
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China.
Shi X
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, China.
Liu L
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Zhao J
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, Guangzhou, China.
Wang X
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China. xinquanwang@mail.tsinghua.edu.cn.
Zhang Z
Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China. zhangzheng1975@aliyun.com. The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China. zhangzheng1975@aliyun.com.
Zhang L
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and Beijing Advanced Innovation Center for Structural Biology, School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, China. zhanglinqi@tsinghua.edu.cn.

MeSH

AdultAgedAngiotensin-Converting Enzyme 2Antibodies, NeutralizingAntibodies, ViralB-LymphocytesBetacoronavirusCOVID-19ChildClone CellsCoronavirus InfectionsCross ReactionsCrystallizationCrystallography, X-RayFemaleHumansMaleMiddle AgedModels, MolecularNeutralization TestsPandemicsPeptidyl-Dipeptidase APlasmaPneumonia, ViralSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32454513

Citation

Ju, Bin, et al. "Human Neutralizing Antibodies Elicited By SARS-CoV-2 Infection." Nature, vol. 584, no. 7819, 2020, pp. 115-119.
Ju B, Zhang Q, Ge J, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020;584(7819):115-119.
Ju, B., Zhang, Q., Ge, J., Wang, R., Sun, J., Ge, X., Yu, J., Shan, S., Zhou, B., Song, S., Tang, X., Yu, J., Lan, J., Yuan, J., Wang, H., Zhao, J., Zhang, S., Wang, Y., Shi, X., ... Zhang, L. (2020). Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature, 584(7819), 115-119. https://doi.org/10.1038/s41586-020-2380-z
Ju B, et al. Human Neutralizing Antibodies Elicited By SARS-CoV-2 Infection. Nature. 2020;584(7819):115-119. PubMed PMID: 32454513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human neutralizing antibodies elicited by SARS-CoV-2 infection. AU - Ju,Bin, AU - Zhang,Qi, AU - Ge,Jiwan, AU - Wang,Ruoke, AU - Sun,Jing, AU - Ge,Xiangyang, AU - Yu,Jiazhen, AU - Shan,Sisi, AU - Zhou,Bing, AU - Song,Shuo, AU - Tang,Xian, AU - Yu,Jinfang, AU - Lan,Jun, AU - Yuan,Jing, AU - Wang,Haiyan, AU - Zhao,Juanjuan, AU - Zhang,Shuye, AU - Wang,Youchun, AU - Shi,Xuanling, AU - Liu,Lei, AU - Zhao,Jincun, AU - Wang,Xinquan, AU - Zhang,Zheng, AU - Zhang,Linqi, Y1 - 2020/05/26/ PY - 2020/03/13/received PY - 2020/05/18/accepted PY - 2020/5/27/pubmed PY - 2020/8/13/medline PY - 2020/5/27/entrez SP - 115 EP - 119 JF - Nature JO - Nature VL - 584 IS - 7819 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32454513/Human_neutralizing_antibodies_elicited_by_SARS_CoV_2_infection_ L2 - https://doi.org/10.1038/s41586-020-2380-z DB - PRIME DP - Unbound Medicine ER -