William N Voss, Y. 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, D. Boutz, Dalton M. Towers, Jonathan R. McDaniel, Daniel Billick, Jule Goike, Lori Rowe, Dhwani Batra, J. Pohl, Justin Lee, Shivaprakash Gangappa, S. Sambhara, M. Gadush, Nianshuang Wang, M. Person, B. Iverson, J. Gollihar, J. Dye, A. Herbert, I. J. Finkelstein, R. Baric, J. McLellan, G. Georgiou, J. Lavinder, G. Ippolito
Science, 2021
A public anti-COVID antibody repertoire Most analyses of the antibody responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have focused on antibodies cloned from memory B cells. This approach has led researchers to conclude that neutralizing antibodies (nAbs) primarily target the receptor-binding domain (RBD) of the virus's spike protein. Voss et al. took a different approach, using proteomic deconvolution of the serum immunoglobulin G antibody repertoire from four COVID-19 convalescent patients. They found that the nAb response was largely directed against epitopes such as the N-terminal domain (NTD), which lie outside the RBD. Several of these nAbs were shared among donors and targeted an NTD epitope that is frequently mutated by variants of concern. Science, abg5268, this issue p. 1108 Plasma immunoglobulin G responses to the SARS-CoV-2 spike contain shared, or “public,” antibodies against a site that is recurrently mutated in variants of concern. 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.
Cited by 26 publications.
Field of study: Medicine