Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5

Cell Discovery

Article

Hongguang Xu¹  Jie Jiao¹  Jun Lu¹  Yanan Zhang¹  Qiaoping Wang¹  Hua Jiang¹  Deyong Song¹  Haifeng Zhao¹  Yanyan Zhao¹  Baiping Sun¹  Rui Li¹  Xin Shao¹  Huimin Zhang¹  Hong Liu¹  Muding Rao¹  Zhenduo Shen¹  Jianxia Feng¹  Ying Li¹  Mengqi Zong¹  Min Li¹  Changlin Dou¹  Chuangchuang Dong¹  Jing Han¹  Xiaoping Yu¹  Beibei Yu¹  Yuanzhu Gao²  Xiaomin Ma²  An Yan²  Ruxi Qi²  Zheng Liu²  Maoqin Duan³  Shuo Liu³  Lan Wang³  Lu Zhang⁴  Xiaodan Ni⁵  Yanxia Wang⁵  Fanhao Meng⁵  Chunna You⁶  Guangying Du⁶  Yanqun Wang⁷  Jincun Zhao⁸ 

[1] Antibody Research and Development Center, Shandong Boan Biotechnology Co., Ltd., Yantai, Shandong, China;Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, Guangdong, China;Division of Monoclonal Antibodies, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, China;Health and Quarantine Laboratory, Guangzhou Customs District Technology Centre, Guangzhou, Guangdong, China;Shuimu BioSciences Ltd, Beijing, China;State Key Laboratory of Long-acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co. Ltd, Yantai, Shandong, China;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, Guangdong, China;GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China;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, Guangdong, China;Guangzhou Laboratory, Bio-Island, Guangzhou, Guangdong, China;Institute of Infectious disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China;Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China;Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China;

DOI  :  10.1038/s41421-022-00509-9

 received in 2022-09-20, accepted in 2022-12-07,  发布年份 2022

来源: Springer

【 摘 要 】

SARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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