Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5
Wang，Yanqun1,2; Yan，An3; Song，Deyong4; Dong，Chuangchuang4; Rao，Muding4; Gao，Yuanzhu3; Qi，Ruxi3; Ma，Xiaomin3; Wang，Qiaoping4; Xu，Hongguang4; Liu，Hong4; Han，Jing4; Duan，Maoqin5; Liu，Shuo5; Yu，Xiaoping4; Zong，Mengqi4; Feng，Jianxia4; Jiao，Jie4; Zhang，Huimin4; Li，Min4; Yu，Beibei4; Wang，Yanxia6; Meng，Fanhao6; Ni，Xiaodan6; Li，Ying4; Shen，Zhenduo4; Sun，Baiping4; Shao，Xin4; Zhao，Haifeng4; Zhao，Yanyan4; Li，Rui4; Zhang，Yanan4; Du，Guangying7; Lu，Jun4; You，Chunna7; Jiang，Hua4; Zhang，Lu8; Wang，Lan5; Dou，Changlin4; Liu，Zheng3; Zhao，Jincun1,9,10,11,12
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.
Cited Times [WOS]:1
|Document Type||Journal Article|
|Department||Cryo-Electron Microscopy Center|
1.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
2.GMU-GIBH Joint School of Life Sciences,Guangzhou Medical University,Guangzhou,Guangdong,China
3.Cryo-electron Microscopy Center,Southern University of Science and Technology,Shenzhen,Guangdong,China
4.Antibody Research and Development Center,Shandong Boan Biotechnology Co.,Ltd.,Yantai,Shandong,China
5.Division of Monoclonal Antibodies,Institute for Biological Product Control,National Institutes for Food and Drug Control (NIFDC),Beijing,China
6.Shuimu BioSciences Ltd,Beijing,China
7.State Key Laboratory of Long-acting and Targeting Drug Delivery System,Shandong Luye Pharmaceutical Co. Ltd,Yantai,Shandong,China
8.Health and Quarantine Laboratory,Guangzhou Customs District Technology Centre,Guangzhou,Guangdong,China
10.Institute of Infectious disease,Guangzhou Eighth People’s Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China
11.Shanghai Institute for Advanced Immunochemical Studies,School of Life Science and Technology,ShanghaiTech University,Shanghai,China
12.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
|Corresponding Author Affilication||School of Medicine; The Third People's Hospital of Shenzhen|
Wang，Yanqun,Yan，An,Song，Deyong,et al. Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5[J]. Cell Discovery,2023,9:3.
Wang，Yanqun.,Yan，An.,Song，Deyong.,Dong，Chuangchuang.,Rao，Muding.,...&Zhao，Jincun.(2023).Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5.Cell Discovery,9,3.
Wang，Yanqun,et al."Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5".Cell Discovery 9(2023):3.
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