Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.

Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
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DOI:
10.1126/science.abg5268
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发表时间:
2021-06-04
期刊:
Science (New York, N.Y.)
影响因子:
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通讯作者:
Ippolito GC
Ippolito GC
中科院分区:
其他
文献类型:
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作者:
Voss WN;Hou YJ;Johnson NV;Delidakis G;Kim JE;Javanmardi K;Horton AP;Bartzoka F;Paresi CJ;Tanno Y;Chou CW;Abbasi SA;Pickens W;George K;Boutz DR;Towers DM;McDaniel JR;Billick D;Goike J;Rowe L;Batra D;Pohl J;Lee J;Gangappa S;Sambhara S;Gadush M;Wang N;Person MD;Iverson BL;Gollihar JD;Dye JM;Herbert AS;Finkelstein IJ;Baric RS;McLellan JS;Georgiou G;Lavinder JJ;Ippolito GC

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SARS-CoV-2感染后在血浆中循环的免疫球蛋白G(IgG)抗体的分子组成和结合表位尚不清楚。在恢复期受试者中,IgG库对刺突糖蛋白的蛋白质组学去卷积揭示了应答主要(>80%)针对位于受体结合结构域(RBD)外部的表位。在一名受试者中,仅四种IgG谱系就占了93.5%的应答,其中包括一种针对N-末端结构域(NTD)的抗体,该抗体对致死性病毒攻击具有保护作用。对多供体类“公共”抗体的遗传、结构和功能表征揭示了NTD表位,该表位在新出现的SARS-CoV-2变异体中反复突变。这些数据表明,“公共”NTD导向和其他非RBD血浆抗体是普遍存在的,并对SARS-CoV-2保护和抗体逃逸有影响。
The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of “public” antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that “public” NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape.
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