首页|Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.The rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus strain.Here,we report two angi-otensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigor-ous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutral-ization against recent variants including currently dominant XBB.1.5.Together,these findings expand our under-standing of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

SARS-CoV-2broad neutralizing antibodyrearrangementsynergistic neutralization

Hui Sun、Tingting Deng、Yali Zhang、Yanling Lin、Yanan Jiang、Yichao Jiang、Yang Huang、Shuo Song、Lingyan Cui、Tingting Li、Hualong Xiong、Miaolin Lan、Liqin Liu、Yu Li、Qianjiao Fang、Kunyu Yu、Wenling Jiang、Lizhi Zhou、Yuqiong Que、Tianying Zhang、Quan Yuan、Tong Cheng、Zheng Zhang、Hai Yu、Jun Zhang、Wenxin Luo、Shaowei Li、Qingbing Zheng、Ying Gu、Ningshao Xia

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State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,School of Public Health,School of Life Sciences,Xiamen University,Xiamen 361102,China

National Institute of Diagnostics and Vaccine Development in Infectious Diseases,School of Public Health,School of Life Sciences,Xiamen University,Xiamen 361102,China

State Key Laboratory of Vaccines for Infectious Diseases,School of Public Health,School of Life Sciences,Xiamen University,Xiamen 361102,China

Xiang An Biomedicine Laboratory,Xiamen 36110

Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen 518112,China

The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen 518112,China

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National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaFujian Natural Science FoundationIndustry-University-Research Project of XiamenFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central UniversitiesNational Postdoctoral Science Foundation of ChinaCAMS Innovation Fund for Medical Sciences

2021YFC23014048199149182272305321709422020J060072022CXY010620720220006207202200042021M7126592019RU022

2024

10.1093/procel/pwad040

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(2)
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