Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.
Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.
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鉴定多种 SARS-CoV-2 变体 RBD 区域内高度保守的中和表位。
DOI：
10.1038/s41467-024-45050-3
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发表时间：
2024-01-29
影响因子：
16.6
通讯作者：
Zhao, Jincun
中科院分区：
文献类型：
--
作者：
Wang, Yanqun;Yan, An;Song, Deyong;Duan, Maoqin;Dong, Chuangchuang;Chen, Jiantao;Jiang, Zihe;Gao, Yuanzhu;Rao, Muding;Feng, Jianxia;Zhang, Zhaoyong;Qi, Ruxi;Ma, Xiaomin;Liu, Hong;Yu, Beibei;Wang, Qiaoping;Zong, Mengqi;Jiao, Jie;Xing, Pingping;Pan, Rongrong;Li, Dan;Xiao, Juxue;Sun, Junbo;Li, Ying;Zhang, Linfeng;Shen, Zhenduo;Sun, Baiping;Zhao, Yanyan;Zhang, Lu;Dai, Jun;Zhao, Jingxian;Wang, Lan;Dou, Changlin;Liu, Zheng;Zhao, Jincun
SARS-CoV-2变异体的不断出现继续削弱现有中和抗体的效力，特别是XBB.1.5和EG.5，它们显示出特殊的免疫逃避特性。在这里，我们鉴定了由广谱中和抗体BA 7535靶向的高度保守的中和表位，其不仅对先前的变体（例如α、β、γ、δ和Omicron BA.1-BA.5），而且对最近出现的Omicron亚变体（包括BF. 7、CH. 1. 1、XBB. 1、XBB. 1. 5、XBB. 1. 9. 1、EG. 5）表现出高中和效力。使用cryo-EM对具有BA 7535-Fab的Omicron Spike三聚体的结构分析表明，BA 7535识别高度保守的隐蔽受体结合结构域（RBD）表位，避免了RBD中的大多数突变热点。此外，基于BA 7535-Fab/RBD复合物相互作用的结构模拟剖析了BA 7535对最新变体的广泛中和作用。单独使用BA 7535或与BA 7208联合使用的治疗性和预防性治疗可保护雌性小鼠免受循环Omicron BA.5和XBB. 1变体感染，表明高度保守的中和表位可作为开发高效治疗性抗体和疫苗的潜在靶标。最近的SARS-CoV-2变种显示出特殊的免疫逃避特性。在这里，作者确定了RBD内的一个高度保守的表位，该表位被广谱中和抗体BA 7535靶向，该抗体在小鼠研究中显示出治疗性抗病毒效力。
The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines. Most recent SARS-CoV-2 variants showed exceptional immune evasion properties. Here, the authors identify a highly conserved epitope within the RBD targeted by a broad spectrum neutralizing antibody BA7535 that shows therapeutic antiviral potency in mouse studies.
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影响因子：
7.3
作者：
通讯作者：
--
影响因子：
64.5
作者：
Nutalai, Rungtiwa;Zhou, Daming;Tuekprakhon, Aekkachai;Ginn, Helen M.;Supasa, Piyada;Liu, Chang;Huo, Jiandong;Mentzer, Alexander J.;Duyvesteyn, Helen M. E.;Dijokaite-Guraliuc, Aiste;Skelly, Donal;Ritter, Thomas G.;Amini, Ali;Bibi, Sagida;Adele, Sandra;Johnson, Sile Ann;Constantinides, Bede;Webster, Hermione;Temperton, Nigel;Klenerman, Paul;Barnes, Eleanor;Dunachie, Susanna J.;Crook, Derrick;Pollard, Andrew J.;Lambe, Teresa;Goulder, Philip;Paterson, Neil G.;Williams, Mark A.;Hall, David R.;Mongkolsapaya, Juthathip;Fry, Elizabeth E.;Dejnirattisai, Wanwisa;Ren, Jingshan;Stuart, David, I;Screaton, Gavin R.
通讯作者：
Screaton, Gavin R.
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S