A human antibody of potent efficacy against SARS-CoV-2 in rhesus macaques showed strong blocking activity to B.1.351.

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 during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), 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.

• Authors: 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
• Journal: mAbs (MAbs) 2021 Jan-Dec Vol. 13 Issue 1 Pg. 1930636 ISSN: 1942-0870 [Electronic] United States
• PMID: 34097570 (Publication Type: Journal Article)

Chemical References

• Antibodies, Neutralizing
• Antiviral Agents
• Epitopes
• JMB2002
• ACE2 protein, human
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (antagonists & inhibitors, genetics, immunology)
• Animals
• Antibodies, Neutralizing (pharmacology)
• Antibody Specificity
• Antiviral Agents (pharmacology)
• Binding Sites, Antibody
• CHO Cells
• COVID-19 (immunology, metabolism, prevention & control, virology)
• Chlorocebus aethiops
• Cricetulus
• Disease Models, Animal
• Epitopes
• Macaca mulatta
• SARS-CoV-2 (drug effects, immunology, pathogenicity)
• Vero Cells
• COVID-19 Drug Treatment