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题名

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

作者
通讯作者Wang,Lan; Dou,Changlin; Liu,Zheng; Zhao,Jincun
共同第一作者Wang,Yanqun; Yan,An; Song,Deyong
发表日期
2023-01-07
DOI
发表期刊
ISSN
2056-5968
EISSN
2056-5968
卷号9期号:1页码:3
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.

相关链接[Scopus记录]
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语种
英语
学校署名
通讯
资助项目
National Key R&D Program of China[
WOS研究方向
Cell Biology
WOS类目
Cell Biology
WOS记录号
WOS:000910153200001
出版者
Scopus记录号
2-s2.0-85145723196
来源库
Scopus
引用统计
被引频次[WOS]:14
成果类型期刊论文
条目标识符http://sustech.caswiz.com/handle/2SGJ60CL/420926
专题冷冻电镜中心
南方科技大学医学院
南方科技大学第二附属医院
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,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
9.Guangzhou Laboratory,Bio-Island,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
通讯作者单位冷冻电镜中心;  南方科技大学医学院;  南方科技大学第二附属医院
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):3.
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),3.
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):3.
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