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

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 RoweDhwani 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

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1108-1112
Number of pages	5
Journal	Science
Volume	372
Issue number	6546
DOIs	https://doi.org/10.1126/science.abg5268
State	Published - Jun 4 2021

Keywords

Animals
Antibodies, Monoclonal/blood
Antibodies, Neutralizing/blood
Antibodies, Viral/blood
Antibody Affinity
COVID-19/immunology
Epitopes/immunology
Humans
Immune Evasion
Immunoglobulin G/blood
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

ASJC Scopus subject areas

General

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10.1126/science.abg5268

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Voss, W. N., Hou, Y. J., Johnson, N. V., Delidakis, G., Kim, J. E., Javanmardi, K., Horton, A. P., Bartzoka, F., Paresi, C. J., Tanno, Y., Chou, C. W., Abbasi, S. A., Pickens, W., George, K., Boutz, D. R., Towers, D. M., McDaniel, J. R., Billick, D., Goike, J., ... Ippolito, G. C. (2021). Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. Science, 372(6546), 1108-1112. https://doi.org/10.1126/science.abg5268

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 & Ippolito, GC 2021, 'Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes', Science, vol. 372, no. 6546, pp. 1108-1112. https://doi.org/10.1126/science.abg5268

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

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.",

keywords = "Animals, Antibodies, Monoclonal/blood, Antibodies, Neutralizing/blood, Antibodies, Viral/blood, Antibody Affinity, COVID-19/immunology, Epitopes/immunology, Humans, Immune Evasion, Immunoglobulin G/blood, 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",

author = "Voss, {William N.} and Hou, {Yixuan J.} and Johnson, {Nicole V.} and George Delidakis and Kim, {Jin Eyun} and Kamyab Javanmardi and Horton, {Andrew P.} and Foteini Bartzoka and Paresi, {Chelsea J.} and Yuri Tanno and Chou, {Chia Wei} and Abbasi, {Shawn A.} and Whitney Pickens and Katia George and Boutz, {Daniel R.} and Towers, {Dalton M.} and McDaniel, {Jonathan R.} and Daniel Billick and Jule Goike and Lori Rowe and Dhwani Batra and Jan Pohl and Justin Lee and Shivaprakash Gangappa and Suryaprakash Sambhara and Michelle Gadush and Nianshuang Wang and Person, {Maria D.} and Iverson, {Brent L.} and Gollihar, {Jimmy D.} and Dye, {John M.} and Herbert, {Andrew S.} and Finkelstein, {Ilya J.} and Baric, {Ralph S.} and McLellan, {Jason S.} and George Georgiou and Lavinder, {Jason J.} and Ippolito, {Gregory C.}",

note = "Publisher Copyright: {\textcopyright} 2021 American Association for the Advancement of Science. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2021",

month = jun,

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doi = "10.1126/science.abg5268",

language = "English (US)",

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pages = "1108--1112",

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T1 - Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes

AU - Voss, William N.

AU - Hou, Yixuan J.

AU - Johnson, Nicole V.

AU - Delidakis, George

AU - Kim, Jin Eyun

AU - Javanmardi, Kamyab

AU - Horton, Andrew P.

AU - Bartzoka, Foteini

AU - Paresi, Chelsea J.

AU - Tanno, Yuri

AU - Chou, Chia Wei

AU - Abbasi, Shawn A.

AU - Pickens, Whitney

AU - George, Katia

AU - Boutz, Daniel R.

AU - Towers, Dalton M.

AU - McDaniel, Jonathan R.

AU - Billick, Daniel

AU - Goike, Jule

AU - Rowe, Lori

AU - Batra, Dhwani

AU - Pohl, Jan

AU - Lee, Justin

AU - Gangappa, Shivaprakash

AU - Sambhara, Suryaprakash

AU - Gadush, Michelle

AU - Wang, Nianshuang

AU - Person, Maria D.

AU - Iverson, Brent L.

AU - Gollihar, Jimmy D.

AU - Dye, John M.

AU - Herbert, Andrew S.

AU - Finkelstein, Ilya J.

AU - Baric, Ralph S.

AU - McLellan, Jason S.

AU - Georgiou, George

AU - Lavinder, Jason J.

AU - Ippolito, Gregory C.

N1 - Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2021/6/4

Y1 - 2021/6/4

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Monoclonal/blood

KW - Antibodies, Neutralizing/blood

KW - Antibodies, Viral/blood

KW - Antibody Affinity

KW - COVID-19/immunology

KW - Epitopes/immunology

KW - Humans

KW - Immune Evasion

KW - Immunoglobulin G/blood

KW - Immunoglobulin Heavy Chains/immunology

KW - Immunoglobulin Variable Region/immunology

KW - Mice

KW - Mice, Inbred BALB C

KW - Mutation

KW - Protein Domains

KW - Proteomics

KW - SARS-CoV-2/genetics

KW - Spike Glycoprotein, Coronavirus/chemistry

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U2 - 10.1126/science.abg5268

DO - 10.1126/science.abg5268

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AN - SCOPUS:85107445328

SN - 0036-8075

VL - 372

SP - 1108

EP - 1112

JO - Science

JF - Science

IS - 6546

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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