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Human IgG cell neutralizing monoclonal antibodies block SARS-CoV-2 infection
Jinkai Wan; Shenghui Xing; Longfei Ding; Yongheng Wang; Dandan Zhu; Bowen Rong; Siqing Wang; Kun Chen; Chenxi He; Songhua Yuan; Chengli Qiu; Chen Zhao; Xiaoyan Zhang; Xiangxi Wang; Yanan Lu; Jianqing Xu; Fei Lan.
Affiliation
  • Jinkai Wan; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Shenghui Xing; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Longfei Ding; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
  • Yongheng Wang; Active Motif China Inc., Shanghai, 201315, China
  • Dandan Zhu; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
  • Bowen Rong; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Siqing Wang; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Kun Chen; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Chenxi He; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
  • Songhua Yuan; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
  • Chengli Qiu; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
  • Chen Zhao; Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
  • Xiaoyan Zhang; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China
  • Xiangxi Wang; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
  • Yanan Lu; Active Motif China Inc., Shanghai, 201315, China
  • Jianqing Xu; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China
  • Fei Lan; Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, L
Preprint in English | bioRxiv | ID: ppbiorxiv-104117
ABSTRACT
The coronavirus induced disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide threat to human lives, and neutralizing antibodies present a great therapeutic potential in curing affected patients. We purified more than one thousand memory B cells specific to SARS-CoV-2 S1 or RBD (receptor binding domain) antigens from 11 convalescent COVID-19 patients, and a total of 729 naturally paired heavy and light chain fragments were obtained by single B cell cloning technology. Among these, 178 recombinant monoclonal antibodies were tested positive for antigen binding, and the top 13 binders with Kd below 0.5 nM are all RBD binders. Importantly, all these 13 antibodies could block pseudoviral entry into HEK293T cells overexpressing ACE2, with the best ones showing IC50s around 2-3 nM. We further identified 8 neutralizing antibodies against authentic virus with IC50s within 10 nM. Among these, 414-1 blocked authentic viral entry at IC50 of 1.75 nM and in combination with 105-38 could achieve IC50 as low as 0.45 nM. Meanwhile, we also found that 3 antibodies could cross-react with the SARS-CoV spike protein. Altogether, our study provided a panel of potent human neutralizing antibodies for COVID19 as therapeutics candidates for further development.
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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2020 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Type of study: Rct Language: English Year: 2020 Document type: Preprint
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