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

William N. Voss(The University of Texas at Austin), Yixuan J. Hou(University of North Carolina at Chapel Hill), Nicole V. Johnson(The University of Texas at Austin), George Delidakis(The University of Texas at Austin), Jin Eyun Kim(The University of Texas at Austin), Kamyab Javanmardi(The University of Texas at Austin), Andrew P. Horton(The University of Texas at Austin), Foteini Bartzoka(The University of Texas at Austin), Chelsea Paresi(The University of Texas at Austin), Yuri Tanno(The University of Texas at Austin), Chia‐Wei Chou(The University of Texas at Austin), Shawn A. Abbasi(United States Army Medical Research Institute of Infectious Diseases), Whitney Pickens(The University of Texas at Austin), Katia George(The University of Texas at Austin), Daniel R. Boutz(The University of Texas at Austin), Dalton M. Towers(The University of Texas at Austin), Jonathan R. McDaniel(Pfizer (United States)), Daniel Billick(The University of Texas at Austin), Jule Goike(The University of Texas at Austin), Lori A. Rowe(Tulane University), Dhwani Batra(Centers for Disease Control and Prevention), Jan Pohl(Centers for Disease Control and Prevention), Justin Lee(Centers for Disease Control and Prevention), Shivaprakash Gangappa(Centers for Disease Control and Prevention), Suryaprakash Sambhara(Centers for Disease Control and Prevention), Michelle Gadush(The University of Texas at Austin), Nianshuang Wang(The University of Texas at Austin), Maria D. Person(The University of Texas at Austin), Brent L. Iverson(The University of Texas at Austin), Jimmy Gollihar(Houston Methodist), John M. Dye(United States Army Medical Research Institute of Infectious Diseases), Andrew S. Herbert(United States Army Medical Research Institute of Infectious Diseases), Ilya J. Finkelstein(The University of Texas at Austin), Ralph S. Baric(University of North Carolina at Chapel Hill), Jason S. McLellan(The University of Texas at Austin), George Georgiou(The University of Texas at Austin), Jason J. Lavinder(The University of Texas at Austin), Gregory C. Ippolito(Houston Methodist)
Science
May 4, 2021
10.1126/science.abg5268
Cited by 291Open Access
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Abstract

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.

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