Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes
William N. Voss, Yixuan J. Hou*, Nicole V. Johnson*, George Delidakis, Jin Eyun Kim, Kamyab Javanmardi, Andrew P. Horton, Foteini Bartzoka, Chelsea J. Paresi, Yuri Tanno, Chia-Wei Chou, Shawn A. Abbasi, Whitney Pickens, Katia George, Daniel R. Boutz, Dalton M. Towers, Jonathan R. McDaniel, Daniel Billick, Jule Goike, Lori Rowe, Dhwani Batra, Jan Pohl, Justin Lee, Shivaprakash Gangappa, Suryaprakash Sambhara, Michelle Gadush, Nianshuang Wang, Maria D. Person, Brent L. Iverson, Jimmy D. Gollihar, John M. Dye, Andrew S. Herbert, Ilya J. Finkelstein, Ralph S. Baric, Jason S. McLellan, George Georgiou, Jason L. Lavinder†, and Gregory C. Ippolito† (* co-first authors; † co-corresponding)
Science, Volume 372, Issue 6546, Pages 1108–1112 (2021)
DOI: 10.1126/science.abg5268
Table of Contents
Abstract
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.
Full Text Availability
The license terms selected by the author(s) for this article do not permit archiving in PMC. The full text is available from the publisher.
References
For the complete references list, please see the full text on PMC or consult the published article in Science 372(6546):1108–1112 (2021).