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A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

Chunyin Gu, Xiaodan Cao, Zongda Wang, Xue Hu, Yanfeng Yao, Yiwu Zhou, Peipei Liu, Xiaowu Liu, Ge Gao, Xiao Hu, Yecheng Zhang, Zhen Chen, Li Gao, Yun Peng, Fangfang Jia, Chao Shan, Li Yu, Kunpeng Liu, Nan Li, Weiwei Guo, Guoping Jiang, Juan Min, Jianjian Zhang, Lu Yang, Meng Shi, Tianquan Hou, Yanan Li, Weichen Liang, Guoqiao Lu, Congyi Yang, Yuting Wang, Kaiwen Xia, Zheng Xiao, Jianhua Xue, Xueyi Huang, Xin Chen, Haixia Ma, Donglin Song, Zhongzong Pan, Xueping Wang, Haibing Guo, Hong Liang, Zhiming Yuan, View ORCID ProfileWuxiang Guan, Su-Jun Deng
doi: https://doi.org/10.1101/2021.02.07.429299
Chunyin Gu
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xiaodan Cao
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Zongda Wang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xue Hu
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Yanfeng Yao
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Yiwu Zhou
4Department of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, People’s Republic of China
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Peipei Liu
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xiaowu Liu
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Ge Gao
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Xiao Hu
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Yecheng Zhang
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Zhen Chen
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Li Gao
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Yun Peng
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Fangfang Jia
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Chao Shan
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Li Yu
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Kunpeng Liu
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Nan Li
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Weiwei Guo
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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Guoping Jiang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Juan Min
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Jianjian Zhang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Lu Yang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Meng Shi
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Tianquan Hou
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Yanan Li
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Weichen Liang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Guoqiao Lu
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Congyi Yang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Yuting Wang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Kaiwen Xia
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Zheng Xiao
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Jianhua Xue
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xueyi Huang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xin Chen
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Haixia Ma
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Donglin Song
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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Zhongzong Pan
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Xueping Wang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Haibing Guo
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Hong Liang
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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Zhiming Yuan
3National Biosafety Laboratory, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China
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  • For correspondence: dengsujun@jemincare.com
Wuxiang Guan
2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China
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  • ORCID record for Wuxiang Guan
  • For correspondence: dengsujun@jemincare.com
Su-Jun Deng
1Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, People’s Republic of China
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  • For correspondence: dengsujun@jemincare.com
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Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

Competing Interest Statement

C. G., X. C., Z. W., P. L., X. L., L. G., F. J., L. Y., N. L., G. J., J. Z., L. Y., M. S., T. H., Y. L., W. L., G. L., C. Y., Y. W., K. X., Z. X., J. X., X. H., X. C., Z. P., X. W., H. G., H. L., and S. D. were employed by Shanghai Jemincare Pharmaceuticals Co., Ltd. All other authors declared no competing interests.

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A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques
Chunyin Gu, Xiaodan Cao, Zongda Wang, Xue Hu, Yanfeng Yao, Yiwu Zhou, Peipei Liu, Xiaowu Liu, Ge Gao, Xiao Hu, Yecheng Zhang, Zhen Chen, Li Gao, Yun Peng, Fangfang Jia, Chao Shan, Li Yu, Kunpeng Liu, Nan Li, Weiwei Guo, Guoping Jiang, Juan Min, Jianjian Zhang, Lu Yang, Meng Shi, Tianquan Hou, Yanan Li, Weichen Liang, Guoqiao Lu, Congyi Yang, Yuting Wang, Kaiwen Xia, Zheng Xiao, Jianhua Xue, Xueyi Huang, Xin Chen, Haixia Ma, Donglin Song, Zhongzong Pan, Xueping Wang, Haibing Guo, Hong Liang, Zhiming Yuan, Wuxiang Guan, Su-Jun Deng
bioRxiv 2021.02.07.429299; doi: https://doi.org/10.1101/2021.02.07.429299
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A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques
Chunyin Gu, Xiaodan Cao, Zongda Wang, Xue Hu, Yanfeng Yao, Yiwu Zhou, Peipei Liu, Xiaowu Liu, Ge Gao, Xiao Hu, Yecheng Zhang, Zhen Chen, Li Gao, Yun Peng, Fangfang Jia, Chao Shan, Li Yu, Kunpeng Liu, Nan Li, Weiwei Guo, Guoping Jiang, Juan Min, Jianjian Zhang, Lu Yang, Meng Shi, Tianquan Hou, Yanan Li, Weichen Liang, Guoqiao Lu, Congyi Yang, Yuting Wang, Kaiwen Xia, Zheng Xiao, Jianhua Xue, Xueyi Huang, Xin Chen, Haixia Ma, Donglin Song, Zhongzong Pan, Xueping Wang, Haibing Guo, Hong Liang, Zhiming Yuan, Wuxiang Guan, Su-Jun Deng
bioRxiv 2021.02.07.429299; doi: https://doi.org/10.1101/2021.02.07.429299

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