A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses

doi:10.1038/s41467-024-49096-1

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	A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses
	Wang, Yingdan 1,2; Hao, Aihua 1; Ji, Ping 1; Ma, Yunping 1,3; Zhang, Zhaoyong 4; Chen, Jiali 1; Mao, Qiyu 1; Xiong, Xinyi4 ; Rehati, Palizhati 1; Wang, Yajie 1; Wang, Yanqun 4; Wen, Yumei 1; Lu, Lu 1; Chen, Zhenguo 1; Zhao, Jincun4,5 ; Wu, Fan 3; Huang, Jinghe 1,2; Sun, Lei 1
	2024-06-15
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	15 期号:1
发表状态	已发表
DOI	10.1038/s41467-024-49096-1
摘要	["The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants.","In this study, the authors develop a potent bispecific antibody targeting two epitopes within the SARS-CoV-2 receptor binding domain and showing robust prophylactic and therapeutic efficacy against XBB.1 infection in mice."]
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收录类别	SCI
语种	英语
资助项目	R&D Program of Guangzhou Laboratory[SRPG22-003] ; Shanghai Municipal Science and Technology Major Project[ZD2021CY001] ; Ministry of Science and Technology of China[2021YFC2302500] ; National Natural Science Foundation of China["32370995","31771008","3197014"] ; National Key Research and Development Program of China[2023YFE0118200] ; Shanghai Municipal Education Commission[22SG16] ; National Science and Technology Major Projects of China["2017ZX10202102","2018ZX10301403"] ; Shanghai Municipal Commission of Health and Family Planning[2018BR08]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:001249166000003
出版者	NATURE PORTFOLIO
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/395893
专题	免疫化学研究所生命科学与技术学院_博士生免疫化学研究所_特聘教授组_赵金存组
通讯作者	Zhao, Jincun; Wu, Fan; Huang, Jinghe; Sun, Lei
作者单位	1.Fudan Univ, Shanghai Peoples Hosp 5, Shanghai Inst Infect Dis & Biosecur, Inst Biomed Sci,Sch Basic Med Sci, Shanghai, Peoples R China 2.Fudan Univ, Shanghai Frontiers Sci Ctr Pathogen Microorganisms, Sch Basic Med Sci, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Affiliated Renji Hosp, Shanghai Immune Therapy Inst, Sch Med, Shanghai, Peoples R China 4.Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis,Natl Clin Res Ctr Resp Dis, Guangzhou 510120, Peoples R China 5.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Wang, Yingdan,Hao, Aihua,Ji, Ping,et al. A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses[J]. NATURE COMMUNICATIONS,2024,15(1).
APA	Wang, Yingdan.,Hao, Aihua.,Ji, Ping.,Ma, Yunping.,Zhang, Zhaoyong.,...&Sun, Lei.(2024).A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses.NATURE COMMUNICATIONS,15(1).
MLA	Wang, Yingdan,et al."A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses".NATURE COMMUNICATIONS 15.1(2024).