1. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
- Author
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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, and Ippolito GC
- Subjects
- Animals, Antibodies, Monoclonal blood, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal immunology, Antibodies, Neutralizing blood, Antibodies, Neutralizing chemistry, Antibodies, Viral blood, Antibodies, Viral chemistry, Antibody Affinity, COVID-19 prevention & control, Epitopes immunology, Humans, Immune Evasion, Immunoglobulin G blood, Immunoglobulin G chemistry, Immunoglobulin Heavy Chains immunology, Immunoglobulin Variable Region immunology, Mice, Mice, Inbred BALB C, Mutation, Protein Domains, Proteomics, SARS-CoV-2 genetics, Spike Glycoprotein, Coronavirus chemistry, Spike Glycoprotein, Coronavirus genetics, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, Immunoglobulin G immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology
- 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., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2021
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