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

doi:10.1038/s41421-022-00509-9

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	Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5
	Wang, Yanqun 1,2; Yan, An 3; Song, Deyong 4; Dong, Chuangchuang 4; Rao, Muding 4; Gao, Yuanzhu 3; Qi, Ruxi 3; Ma, Xiaomin 3; Wang, Qiaoping 4; Xu, Hongguang 4; Liu, Hong 4; Han, Jing 4; Duan, Maoqin 5; Liu, Shuo 5; Yu, Xiaoping 4; Zong, Mengqi 4; Feng, Jianxia 4; Jiao, Jie 4; Zhang, Huimin 4; Li, Min 4; Yu, Beibei 4; Wang, Yanxia 6; Meng, Fanhao 6; Ni, Xiaodan 6; Li, Ying 4; Shen, Zhenduo 4; Sun, Baiping 4; Shao, Xin 4; Zhao, Haifeng 4; Zhao, Yanyan 4; Li, Rui 4; Zhang, Yanan 4; Du, Guangying 7; Lu, Jun 4; You, Chunna 7; Jiang, Hua 4; Zhang, Lu 8; Wang, Lan 5; Dou, Changlin 4; Liu, Zheng 3; Zhao, Jincun1,9,10,11,12
	2023-12-01
发表期刊	CELL DISCOVERY; (IF:13.0[JCR-2023],14.8[5-Year])
ISSN	2056-5968
EISSN	2056-5968
卷号	9 期号:1
DOI	10.1038/s41421-022-00509-9
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.
学科门类	Biochemistry ; Molecular Biology ; Genetics ; Cell Biology
URL	查看原文
收录类别	SCOPUS
语种	英语
原始文献类型	Article
Scopus 记录号	2-s2.0-85145723196
来源库	SCOPUS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286436
专题	免疫化学研究所免疫化学研究所_特聘教授组_赵金存组
作者单位	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,Guangdong,Guangzhou,China; 2.GMU-GIBH Joint School of Life Sciences,Guangzhou Medical University,Guangdong,Guangzhou,China; 3.Cryo-electron Microscopy Center,Southern University of Science and Technology,Guangdong,Shenzhen,China; 4.Antibody Research and Development Center,Shandong Boan Biotechnology Co.,Ltd.,Shandong,Yantai,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,Shandong,Yantai,China; 8.Health and Quarantine Laboratory,Guangzhou Customs District Technology Centre,Guangdong,Guangzhou,China; 9.Guangzhou Laboratory,Bio-Island,Guangdong,Guangzhou,China; 10.Institute of Infectious disease,Guangzhou Eighth People’s Hospital of Guangzhou Medical University,Guangdong,Guangzhou,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,Guangdong,Shenzhen,China
推荐引用方式 GB/T 7714	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(1).
APA	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(1).
MLA	Wang, Yanqun,et al."Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5".CELL DISCOVERY; 9.1(2023).