Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant.
Evasion of neutralizing antibody responses by the SARS-CoV-2 BA.2.75 variant.
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DOI：
10.1016/j.chom.2022.09.015
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发表时间：
2022-11-09
影响因子：
30.3
通讯作者：
Liu, Shan-Lu
中科院分区：
文献类型：
--
作者：
Qu, Panke;Evans, John P.;Zheng, Yi-Min;Carlin, Claire;Saif, Linda J.;Oltz, Eugene M.;Xu, Kai;Gumina, Richard J.;Liu, Shan-Lu
新出现的BA.2.75严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）变体与祖先的BA.2变体相比，其刺突(S)蛋白中含有9个额外的突变。在这里，我们研究了BA.2.75在mrna接种和ba .1感染个体中的中和抗体逃逸，以及s功能变化的分子基础。值得注意的是，BA.2.75比BA.2表现出增强的中和抗性，但低于BA.4/5变体。BA.2.75的G446S和N460K突变是其增强对中和抗体抗性的主要原因。R493Q突变是对原型序列的回归，降低了BA.2.75的中和抗性。这些突变的影响与它们在常见中和抗体表位中的位置一致。此外，BA.2.75比BA.2表现出更强的细胞-细胞融合，这主要是由N460K突变驱动的，该突变增强了S加工。结构模型显示N460K增加了受体接触，提示受体利用增强和合胞体形成的机制。新出现的欧米克隆亚变体再次引发了人们对逃避现有免疫的担忧。Qu和同事比较了BA.2.75与先前变异的免疫抗性和融合原性。BA.2.75比BA.2具有更强的中和抗性，但比BA.4/5弱，并且融合原性增强，这主要是由G446S和N460K驱动的。
The newly emerged BA.2.75 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant contains 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here, we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in S. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2 but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The impact of these mutations is consistent with their locations in common neutralizing antibody epitopes. Further, BA.2.75 shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling reveals enhanced receptor contacts introduced by N460K, suggesting a mechanism of potentiated receptor utilization and syncytia formation. Newly emerged Omicron subvariants reignite concerns over escape from existing immunity. Qu and colleagues compare the immunity resistance and fusogenicity of BA.2.75 with prior variants. BA.2.75 exhibits stronger neutralization resistance than BA.2 but weaker than BA.4/5, as well as enhanced fusogenicity, which are largely driven by G446S and N460K, respectively.
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影响因子：
16.6
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
通讯作者：
Bloom JD
影响因子：
64.5
作者：
Li, Linjie;Liao, Hanyi;Meng, Yumin;Li, Weiwei;Han, Pengcheng;Liu, Kefang;Wang, Qing;Li, Dedong;Zhang, Yanfang;Wang, Liang;Fan, Zheng;Zhang, Yuqin;Wang, Qiyue;Zhao, Xin;Sun, Yeping;Huang, Niu;Qi, Jianxun;Gao, George Fu
通讯作者：
Gao, George Fu
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
影响因子：
30.3
作者：
Evans, John P.;Zeng, Cong;Qu, Panke;Faraone, Julia;Zheng, Yi-Min;Carlin, Claire;Bednash, Joseph S.;Zhou, Tongqing;Lozanski, Gerard;Mallampalli, Rama;Saif, Linda J.;Oltz, Eugene M.;Mohler, Peter J.;Xu, Kai;Gumina, Richard J.;Liu, Shan-Lu
通讯作者：
Liu, Shan-Lu
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.