Neutralization, effector function and immune imprinting of Omicron variants.
Neutralization, effector function and immune imprinting of Omicron variants.
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DOI：
10.1038/s41586-023-06487-6
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发表时间：
2023-09
期刊：
影响因子：
64.8
通讯作者：
Veesler, David
中科院分区：
文献类型：
--
作者：
Addetia, Amin;Piccoli, Luca;Case, James Brett;Park, Young-Jun;Beltramello, Martina;Guarino, Barbara;Dang, Ha;de Melo, Guilherme Dias;Pinto, Dora;Sprouse, Kaitlin;Scheaffer, Suzanne M.;Bassi, Jessica;Silacci-Fregni, Chiara;Muoio, Francesco;Dini, Marco;Vincenzetti, Lucia;Acosta, Rima;Johnson, Daisy;Subramanian, Sambhavi;Saliba, Christian;Giurdanella, Martina;Lombardo, Gloria;Leoni, Giada;Culap, Katja;Mcalister, Carley;Rajesh, Anushka;Dellota, Exequiel;Zhou, Jiayi;Farhat, Nisar;Bohan, Dana;Noack, Julia;Chen, Alex;Lempp, Florian A.;Quispe, Joel;Kergoat, Lauriane;Larrous, Florence;Cameroni, Elisabetta;Whitener, Bradley;Giannini, Olivier;Cippa, Pietro;Ceschi, Alessandro;Ferrari, Paolo;Franzetti-Pellanda, Alessandra;Biggiogero, Maira;Garzoni, Christian;Zappi, Stephanie;Bernasconi, Luca;Kim, Min Jeong;Rosen, Laura E.;Schnell, Gretja;Czudnochowski, Nadine;Benigni, Fabio;Franko, Nicholas;Logue, Jennifer K.;Yoshiyama, Courtney;Stewart, Cameron;Chu, Helen;Bourhy, Herve;Schmid, Michael A.;Purcell, Lisa A.;Snell, Gyorgy;Lanzavecchia, Antonio;Diamond, Michael S.;Corti, Davide;Veesler, David
目前流行的SARS-CoV-2变体在刺突蛋白的受体结合结构域（RBD）的热点处获得了会聚突变。这些突变对病毒感染和传播的影响以及疫苗和治疗的有效性仍然知之甚少。在这里，我们证明，最近出现的BQ.1.1和XBB.1.5变种结合宿主ACE 2具有高亲和力，并促进膜融合更有效地比早期的Omicron变种。与S309抗体（sotrovimab的亲本抗体）和人ACE 2的片段抗原结合区结合的BQ.1.1、XBB.1和BN. 1 RBD的结构解释了通过构象选择、改变的ACE 2识别和免疫逃避保持抗体结合。我们发现，sotrovimab与所有Omicron变体紧密结合，促进Fc依赖性效应子功能，并保护BQ.1.1激发的小鼠和XBB.1.5激发的仓鼠。疫苗引发的人血浆抗体与当前Omicron变体交叉反应并触发针对当前Omicron变体的效应子功能，尽管中和活性降低，表明了针对疾病的保护机制，例如S309。交叉反应的RBD指导的人类记忆B细胞仍然占主导地位，即使在两次暴露于Omicron尖峰，强调了持久的免疫印迹的作用。目前流行的SARS-CoV-2 Omicron变异体刺突蛋白热点的会聚突变增加了对宿主受体的结合亲和力，并促进与宿主细胞膜的更有效融合。
Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting. Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.
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DOI：
10.1126/science.abq0203
发表时间：
2022-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Cao, Yunlong;Yisimayi, Ayijiang;Jian, Fanchong;Song, Weiliang;Xiao, Tianhe;Wang, Lei;Du, Shuo;Wang, Jing;Li, Qianqian;Chen, Xiaosu;Yu, Yuanling;Wang, Peng;Zhang, Zhiying;Liu, Pulan;An, Ran;Hao, Xiaohua;Wang, Yao;Feng, Rui;Sun, Haiyan;Zhao, Lijuan;Zhang, Wen;Zhao, Dong;Zheng, Jiang;Yu, Lingling;Li, Can;Zhang, Na;Wang, Rui;Niu, Xiao;Yang, Sijie;Song, Xuetao;Chai, Yangyang;Hu, Ye;Shi, Yansong;Zheng, Linlin;Li, Zhiqiang;Gu, Qingqing;Shao, Fei;Huang, Weijin;Jin, Ronghua;Shen, Zhongyang;Wang, Youchun;Wang, Xiangxi;Xiao, Junyu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney
影响因子：
2.2
作者：
Chen, Shaoxia;McMullan, Greg;Faruqi, Abdul R.;Murshudov, Garib N.;Short, Judith M.;Scheres, Sjors H. W.;Henderson, Richard
通讯作者：
Henderson, Richard
影响因子：
64.8
作者：
Cho A;Muecksch F;Schaefer-Babajew D;Wang Z;Finkin S;Gaebler C;Ramos V;Cipolla M;Mendoza P;Agudelo M;Bednarski E;DaSilva J;Shimeliovich I;Dizon J;Daga M;Millard KG;Turroja M;Schmidt F;Zhang F;Tanfous TB;Jankovic M;Oliveria TY;Gazumyan A;Caskey M;Bieniasz PD;Hatziioannou T;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
17.1
作者：
Bartsch YC;Tong X;Kang J;Avendaño MJ;Serrano EF;García-Salum T;Pardo-Roa C;Riquelme A;Cai Y;Renzi I;Stewart-Jones G;Chen B;Medina RA;Alter G
通讯作者：
Alter G