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

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Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes
Science ( IF 56.9 ) Pub Date : 2021-06-04 , DOI: 10.1126/science.abg5268
William N Voss ₁ , Yixuan J Hou ₂ , Nicole V Johnson ₁ , George Delidakis ₃ , Jin Eyun Kim ₄ , Kamyab Javanmardi ₁ , Andrew P Horton ₁ , Foteini Bartzoka ₁ , Chelsea J Paresi ₅ , Yuri Tanno ₃ , Chia-Wei Chou ₁ , Shawn A Abbasi ₆ , Whitney Pickens ₁ , Katia George ₁ , Daniel R Boutz _{1,

7} , Dalton M Towers ₃ , Jonathan R McDaniel ₈ , Daniel Billick ₁ , Jule Goike ₁ , Lori Rowe _{9,

10} , Dhwani Batra ₉ , Jan Pohl ₉ , Justin Lee ₉ , Shivaprakash Gangappa ₁₁ , Suryaprakash Sambhara ₁₁ , Michelle Gadush ₁₂ , Nianshuang Wang ₁ , Maria D Person ₁₂ , Brent L Iverson ₅ , Jimmy D Gollihar _{1,

7,

13} , John M Dye ₆ , Andrew S Herbert ₆ , Ilya J Finkelstein ₁ , Ralph S Baric _{2,

14} , Jason S McLellan ₁ , George Georgiou _{1,

3,

4,

15} , Jason J Lavinder _{1,

3} , Gregory C Ippolito _{1,

13,

15}

Affiliation

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
CCDC Army Research Laboratory-South, The University of Texas at Austin, Austin, TX, USA.
Biomedicine Design, Pfizer, Cambridge, MA, USA.
Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Tulane National Primate Research Center Department of Microbiology 18703 Three Rivers Road Covington, LA, USA.
Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.

The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (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 amino (N)-terminal domain (NTD)–directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multidonor 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.

中文翻译：

SARS-CoV-2 非 RBD 刺突表位的普遍、保护性和会聚 IgG 识别

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染后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。对恢复期受试者中的 IgG 库与刺突糖蛋白进行蛋白质组学解卷积，结果表明反应主要 (>80%) 针对位于受体结合域 (RBD) 外部的表位。在一名受试者中，仅四种 IgG 谱系就占了 93.5% 的反应，其中包括氨基 (N) 末端结构域 (NTD) 定向抗体，可防止致命病毒攻击。对一类多供体“公共”抗体的遗传、结构和功能特征揭示了一个 NTD 表位，该表位在新出现的 SARS-CoV-2 令人关注的变体中经常发生突变。这些数据表明，“公共”NTD 定向抗体和其他非 RBD 血浆抗体很普遍，并且对 SARS-CoV-2 保护和抗体逃逸具有影响。

更新日期：2021-06-04

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