BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.
复制标题
DOI：
10.1038/s41586-022-04980-y
复制
发表时间：
2022-08
期刊：
影响因子：
64.8
通讯作者：
Xie, Xiaoliang Sunney
中科院分区：
文献类型：
--
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
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）Omicron亚系BA.2.12.1、BA.4和BA.5表现出比BA.2谱系更高的传播性。这些最近出现的变体的受体结合和免疫逃避能力需要立即调查。在这里，加上刺突蛋白的结构比较，我们表明，BA.2.12.1，BA.4和BA.5（BA.4和BA.5以下统称为BA.4/BA.5）表现出类似的结合亲和力BA.2的血管紧张素转换酶2（ACE 2）受体。值得注意的是，与BA.2相比，BA.2.12.1和BA.4/BA.5显示出对来自三联疫苗接种个体或来自疫苗接种后发生BA.1感染的个体的血浆的中和抗体逃避增加。为了描述潜在的抗体逃避机制，我们确定了针对病毒刺突蛋白受体结合结构域的1，640种中和抗体的逃避突变谱，表位分布和O-中和效率，其中包括从BA.1感染恢复的人中分离的614种抗体。接种疫苗后的BA.1感染主要唤起针对祖先（下文称为野生型（WT））SARS-CoV-2刺突蛋白的体液免疫记忆。所产生的引发抗体可以中和WT SARS-CoV-2和BA. 1，并且富集在刺突上不结合ACE 2的表位上。然而，这些交叉反应性中和抗体中的大多数被刺突突变体L452 Q、L452 R和F486 V避开。BA.1感染还可以诱导BA.1特异性抗体的新克隆，其有效地中和BA.1。然而，由于D405 N和F486 V突变，这些中和抗体在很大程度上被BA.2和BA.4/BA.5逃避，并且对前Omicron变体反应弱，表现出窄的中和宽度。治疗性中和抗体bebtelovimab和cigavimab可以有效地中和BA.2.12.1和BA.4/BA.5，而S371 F、D405 N和R408 S突变破坏了大多数广泛的肉瘤病毒中和抗体。总之，我们的研究结果表明，Omicron可能会进化突变，以逃避BA.1感染引起的体液免疫，这表明BA.1衍生的疫苗加强剂可能无法实现对新Omicron变体的广谱保护。对SARS-CoV-2 Omicron亚变体的抗体和刺突蛋白之间相互作用的生物化学和结构研究表明，这些变体如何进化以逃避抗体介导的中和。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles, epitope distribution and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab and cilgavimab can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. Biochemical and structural studies of the interactions between antibodies and spike proteins from SARS-CoV-2 Omicron subvariants indicate how these variants have evolved to escape antibody-mediated neutralization.
登录
查看更多内容
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：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
17.1
作者：
Jones BE;Brown-Augsburger PL;Corbett KS;Westendorf K;Davies J;Cujec TP;Wiethoff CM;Blackbourne JL;Heinz BA;Foster D;Higgs RE;Balasubramaniam D;Wang L;Zhang Y;Yang ES;Bidshahri R;Kraft L;Hwang Y;Žentelis S;Jepson KR;Goya R;Smith MA;Collins DW;Hinshaw SJ;Tycho SA;Pellacani D;Xiang P;Muthuraman K;Sobhanifar S;Piper MH;Triana FJ;Hendle J;Pustilnik A;Adams AC;Berens SJ;Baric RS;Martinez DR;Cross RW;Geisbert TW;Borisevich V;Abiona O;Belli HM;de Vries M;Mohamed A;Dittmann M;Samanovic MI;Mulligan MJ;Goldsmith JA;Hsieh CL;Johnson NV;Wrapp D;McLellan JS;Barnhart BC;Graham BS;Mascola JR;Hansen CL;Falconer E
通讯作者：
Falconer E
影响因子：
64.5
作者：
Cui Z;Liu P;Wang N;Wang L;Fan K;Zhu Q;Wang K;Chen R;Feng R;Jia Z;Yang M;Xu G;Zhu B;Fu W;Chu T;Feng L;Wang Y;Pei X;Yang P;Xie XS;Cao L;Cao Y;Wang X
通讯作者：
Wang X