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 J Lavinder; Gregory C Ippolito

doi:10.1126/science.abg5268

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

Science. 2021 Jun 4;372(6546):1108-1112. doi: 10.1126/science.abg5268. Epub 2021 May 4.

Authors

William N Voss¹, Yixuan J Hou^#², Nicole V Johnson^#¹, George Delidakis³, Jin Eyun Kim⁴, Kamyab Javanmardi¹, Andrew P Horton¹, Foteini Bartzoka¹, Chelsea J Paresi⁵, Yuri Tanno³, Chia-Wei Chou¹, Shawn A Abbasi⁶, Whitney Pickens¹, Katia George¹, Daniel R Boutz^{1

7}, Dalton M Towers³, Jonathan R McDaniel⁸, Daniel Billick¹, Jule Goike¹, Lori Rowe^{9

10}, Dhwani Batra⁹, Jan Pohl⁹, Justin Lee⁹, Shivaprakash Gangappa¹¹, Suryaprakash Sambhara¹¹, Michelle Gadush¹², Nianshuang Wang¹, Maria D Person¹², Brent L Iverson⁵, Jimmy D Gollihar^{1

7

13}, John M Dye⁶, Andrew S Herbert⁶, Ilya J Finkelstein¹, Ralph S Baric^{2

14}, Jason S McLellan¹, George Georgiou^{1

3

4

15}, Jason J Lavinder^{16

3}, Gregory C Ippolito^{16

13

15}

Affiliations

¹ Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
² Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
⁴ Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
⁵ Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
⁶ U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
⁷ CCDC Army Research Laboratory-South, The University of Texas at Austin, Austin, TX, USA.
⁸ Biomedicine Design, Pfizer, Cambridge, MA, USA.
⁹ Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹⁰ Tulane National Primate Research Center Department of Microbiology 18703 Three Rivers Road Covington, LA, USA.
¹¹ Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
¹² Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
¹³ Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
¹⁴ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁵ Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
¹⁶ Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. jlavinder@utexas.edu gci@utexas.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antibodies, Monoclonal / blood
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / chemistry
Antibodies, Neutralizing / immunology*
Antibodies, Viral / blood
Antibodies, Viral / chemistry
Antibodies, Viral / immunology*
Antibody Affinity
COVID-19 / immunology*
COVID-19 / prevention & control
Epitopes / immunology
Humans
Immune Evasion
Immunoglobulin G / blood
Immunoglobulin G / chemistry
Immunoglobulin G / immunology*
Immunoglobulin Heavy Chains / immunology
Immunoglobulin Variable Region / immunology
Mice
Mice, Inbred BALB C
Mutation
Protein Domains
Proteomics
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Epitopes
Immunoglobulin G
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding