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

• Published in: Science Vol. 372; no. 6546; pp. 1108 - 1112
• Main Authors: Voss, William N, Hou, Yixuan J, Johnson, Nicole V, Delidakis, George, Kim, Jin Eyun, Javanmardi, Kamyab, Horton, Andrew P, Bartzoka, Foteini, Paresi, Chelsea J, Tanno, Yuri, Chou, Chia-Wei, Abbasi, Shawn A, Pickens, Whitney, George, Katia, Boutz, Daniel R, Towers, Dalton M, McDaniel, Jonathan R, Billick, Daniel, Goike, Jule, Rowe, Lori, Batra, Dhwani, Pohl, Jan, Lee, Justin, Gangappa, Shivaprakash, Sambhara, Suryaprakash, Gadush, Michelle, Wang, Nianshuang, Person, Maria D, Iverson, Brent L, Gollihar, Jimmy D, Dye, John, Herbert, Andrew, Finkelstein, Ilya J, Baric, Ralph S, McLellan, Jason S, Georgiou, George, Lavinder, Jason J, Ippolito, Gregory C
• Format: Journal Article Web Resource
• Language: English
• Published: United States The American Association for the Advancement of Science 04.06.2021; American Association for the Advancement of Science
• Subjects: Antibodies; Binding; Blood plasma; Chemical composition; Coronaviruses; COVID-19; Deconvolution; Domains; Epitopes; Glycoproteins; IgG antibody; Immunoglobulin G; Immunoglobulins; Immunological memory; Immunology; Infections; Lymphocytes B; Medical research; Memory cells; Microbio; Receptors; Respiratory diseases; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike glycoprotein; Spike protein; Structural analysis; Structure-function relationships; Viral diseases; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abg5268

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.