Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages
Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages
Abstract SARS-CoV-2 variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding working mechanisms and developing therapeutic agents. In this study, we characterized previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-EM structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.
Wang Xinquan、Yin Qiangling、Wang Zejun、Shan Sisi、Zhang Laixing、Sun Lina、Jing Zhaofei、Wu Wei、Shi Xuanling、Li Jiandong、Wang Shiwen、Yang Maojun、Liang Mifang、Huang Tao、Yu Jinfang、Li Xiaoman、Qu Yuanyuan、Gui Fang、Li Xinguo、Pan Yongbing、Yang Xiaoming、Lu Jia、Duan Kai、Li Dexin、Zhang Linqi
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.NexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionNational Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionNexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua UniversityState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention||CDC-WIV Joint Research Center for Emerging Diseases and BiosafetyThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention||CDC-WIV Joint Research Center for Emerging Diseases and BiosafetyState Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and PreventionThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityThe Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityInstitution of Infectious Diseases, Shenzhen Bay LaboratoryNational Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd.State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention||CDC-WIV Joint Research Center for Emerging Diseases and BiosafetyNexVac Research Center, Comprehensive AIDS Research Center, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
医药卫生理论医学研究方法基础医学
Wang Xinquan,Yin Qiangling,Wang Zejun,Shan Sisi,Zhang Laixing,Sun Lina,Jing Zhaofei,Wu Wei,Shi Xuanling,Li Jiandong,Wang Shiwen,Yang Maojun,Liang Mifang,Huang Tao,Yu Jinfang,Li Xiaoman,Qu Yuanyuan,Gui Fang,Li Xinguo,Pan Yongbing,Yang Xiaoming,Lu Jia,Duan Kai,Li Dexin,Zhang Linqi.Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.05.27.493682.点此复制
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