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Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection.
Cell Rep. 2020 Jul 21; 32(3):107918.CR

Abstract

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.

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Authors+Show Affiliations

Wan J
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Xing S
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ding L
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Wang Y
Active Motif China, Inc., Shanghai 201315, China.
Gu C
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wu Y
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Rong B
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Li C
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wang S
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chen K
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
He C
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhu D
National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Yuan S
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Qiu C
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Zhao C
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Nie L
Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou City, Zhejiang Province 318000, China.
Gao Z
Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou City, Zhejiang Province 318000, China.
Jiao J
Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou City, Zhejiang Province 318000, China.
Zhang X
Shanghai Public Health Clinical Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China.
Wang X
National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Ying T
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wang H
Zhejiang Hisun Pharmaceutical Co., Ltd., Taizhou City, Zhejiang Province 318000, China.
Xie Y
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: yhxie@fudan.edu.cn.
Lu Y
Active Motif China, Inc., Shanghai 201315, China. Electronic address: ylu@activemotif.com.
Xu J
Shanghai Public Health Clinical Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China. Electronic address: xujianqing@shphc.org.cn.
Lan F
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: fei_lan@fudan.edu.cn.

MeSH

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralB-LymphocytesBetacoronavirusCOVID-19Coronavirus InfectionsEpitope MappingEpitopesHumansImmunologic MemoryNeutralization TestsPandemicsPneumonia, ViralProtein DomainsReceptors, VirusSARS-CoV-2Spike Glycoprotein, Coronavirus

Pub Type(s)

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

Language

eng

PubMed ID

32668215

Citation

Wan, Jinkai, et al. "Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection." Cell Reports, vol. 32, no. 3, 2020, p. 107918.
Wan J, Xing S, Ding L, et al. Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. Cell Rep. 2020;32(3):107918.
Wan, J., Xing, S., Ding, L., Wang, Y., Gu, C., Wu, Y., Rong, B., Li, C., Wang, S., Chen, K., He, C., Zhu, D., Yuan, S., Qiu, C., Zhao, C., Nie, L., Gao, Z., Jiao, J., Zhang, X., ... Lan, F. (2020). Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. Cell Reports, 32(3), 107918. https://doi.org/10.1016/j.celrep.2020.107918
Wan J, et al. Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. Cell Rep. 2020 Jul 21;32(3):107918. PubMed PMID: 32668215.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. AU - Wan,Jinkai, AU - Xing,Shenghui, AU - Ding,Longfei, AU - Wang,Yongheng, AU - Gu,Chenjian, AU - Wu,Yanling, AU - Rong,Bowen, AU - Li,Cheng, AU - Wang,Siqing, AU - Chen,Kun, AU - He,Chenxi, AU - Zhu,Dandan, AU - Yuan,Songhua, AU - Qiu,Chengli, AU - Zhao,Chen, AU - Nie,Lei, AU - Gao,Zhangzhao, AU - Jiao,Jingyu, AU - Zhang,Xiaoyan, AU - Wang,Xiangxi, AU - Ying,Tianlei, AU - Wang,Haibin, AU - Xie,Youhua, AU - Lu,Yanan, AU - Xu,Jianqing, AU - Lan,Fei, Y1 - 2020/07/03/ PY - 2020/5/27/received PY - 2020/6/16/revised PY - 2020/6/25/accepted PY - 2020/7/16/pubmed PY - 2020/8/4/medline PY - 2020/7/16/entrez KW - COVID-19 KW - RBD KW - SARS-CoV-2 KW - coronavirus KW - cross-neutralizing antibody KW - epitope KW - human antibodies KW - infection KW - neutralizing antibodies KW - spike protein SP - 107918 EP - 107918 JF - Cell reports JO - Cell Rep VL - 32 IS - 3 N2 - Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/32668215/Human_IgG_Neutralizing_Monoclonal_Antibodies_Block_the_SARS_CoV_2_Infection_ DB - PRIME DP - Unbound Medicine ER -