Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Christopher O. Barnes; Anthony P. West; Kathryn E. Huey-Tubman; Magnus A.G. Hoffmann; Naima G. Sharaf; Pauline R. Hoffman; Nicholas Koranda; Harry B. Gristick; Christian Gaebler; Frauke Muecksch; Julio C.Cetrulo Lorenzi; Shlomo Finkin; Thomas Hägglöf; Arlene Hurley; Katrina G. Millard; Yiska Weisblum; Fabian Schmidt; Theodora Hatziioannou; Paul D. Bieniasz; Marina Caskey; Davide F. Robbiani; Michel C. Nussenzweig; Pamela J. Bjorkman

doi:10.1016/j.cell.2020.06.025

Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Christopher O. Barnes
, Anthony P. West
, Kathryn E. Huey-Tubman
, Magnus A.G. Hoffmann
, Naima G. Sharaf
, Pauline R. Hoffman
, Nicholas Koranda
, Harry B. Gristick
, Christian Gaebler
, Frauke Muecksch
, Julio C.Cetrulo Lorenzi
, Shlomo Finkin
, Thomas Hägglöf
, Arlene Hurley
, Katrina G. Millard
, Yiska Weisblum
, Fabian Schmidt
, Theodora Hatziioannou
, Paul D. Bieniasz
, Marina Caskey

Davide F. Robbiani, Michel C. Nussenzweig^*, Pamela J. Bjorkman^*

^*Corresponding author for this work

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

569 Scopus citations

Abstract

Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1^A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

Original language	English
Pages (from-to)	828-842.e16
Journal	Cell
Volume	182
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2020.06.025
State	Published - 20 Aug 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 The Author(s)

Keywords

COVID-19
ELISA
Fab
IgG
MERS-CoV
SARS-CoV
SARS-CoV-2
convalescent plasma
coronavirus
electron microscopy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2020.06.025

Cite this

Barnes, C. O., West, A. P., Huey-Tubman, K. E., Hoffmann, M. A. G., Sharaf, N. G., Hoffman, P. R., Koranda, N., Gristick, H. B., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Finkin, S., Hägglöf, T., Hurley, A., Millard, K. G., Weisblum, Y., Schmidt, F., Hatziioannou, T., Bieniasz, P. D., ... Bjorkman, P. J. (2020). Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies. Cell, 182(4), 828-842.e16. https://doi.org/10.1016/j.cell.2020.06.025

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title = "Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies",

abstract = "Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 {\AA} cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.",

keywords = "COVID-19, ELISA, Fab, IgG, MERS-CoV, SARS-CoV, SARS-CoV-2, convalescent plasma, coronavirus, electron microscopy",

author = "Barnes, \{Christopher O.\} and West, \{Anthony P.\} and Huey-Tubman, \{Kathryn E.\} and Hoffmann, \{Magnus A.G.\} and Sharaf, \{Naima G.\} and Hoffman, \{Pauline R.\} and Nicholas Koranda and Gristick, \{Harry B.\} and Christian Gaebler and Frauke Muecksch and Lorenzi, \{Julio C.Cetrulo\} and Shlomo Finkin and Thomas H{\"a}ggl{\"o}f and Arlene Hurley and Millard, \{Katrina G.\} and Yiska Weisblum and Fabian Schmidt and Theodora Hatziioannou and Bieniasz, \{Paul D.\} and Marina Caskey and Robbiani, \{Davide F.\} and Nussenzweig, \{Michel C.\} and Bjorkman, \{Pamela J.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = aug,

day = "20",

doi = "10.1016/j.cell.2020.06.025",

language = "אנגלית",

volume = "182",

pages = "828--842.e16",

journal = "Cell",

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Barnes, CO, West, AP, Huey-Tubman, KE, Hoffmann, MAG, Sharaf, NG, Hoffman, PR, Koranda, N, Gristick, HB, Gaebler, C, Muecksch, F, Lorenzi, JCC, Finkin, S, Hägglöf, T, Hurley, A, Millard, KG, Weisblum, Y, Schmidt, F, Hatziioannou, T, Bieniasz, PD, Caskey, M, Robbiani, DF, Nussenzweig, MC & Bjorkman, PJ 2020, 'Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies', Cell, vol. 182, no. 4, pp. 828-842.e16. https://doi.org/10.1016/j.cell.2020.06.025

TY - JOUR

T1 - Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

AU - Barnes, Christopher O.

AU - West, Anthony P.

AU - Huey-Tubman, Kathryn E.

AU - Hoffmann, Magnus A.G.

AU - Sharaf, Naima G.

AU - Hoffman, Pauline R.

AU - Koranda, Nicholas

AU - Gristick, Harry B.

AU - Gaebler, Christian

AU - Muecksch, Frauke

AU - Lorenzi, Julio C.Cetrulo

AU - Finkin, Shlomo

AU - Hägglöf, Thomas

AU - Hurley, Arlene

AU - Millard, Katrina G.

AU - Weisblum, Yiska

AU - Schmidt, Fabian

AU - Hatziioannou, Theodora

AU - Bieniasz, Paul D.

AU - Caskey, Marina

AU - Robbiani, Davide F.

AU - Nussenzweig, Michel C.

AU - Bjorkman, Pamela J.

PY - 2020/8/20

Y1 - 2020/8/20

N2 - Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

AB - Neutralizing antibody responses to coronaviruses mainly target the receptor-binding domain (RBD) of the trimeric spike. Here, we characterized polyclonal immunoglobulin Gs (IgGs) and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their focus on RBD epitopes, recognition of alpha- and beta-coronaviruses, and contributions of avidity to increased binding/neutralization of IgGs over Fabs. Using electron microscopy, we examined specificities of polyclonal plasma Fabs, revealing recognition of both S1A and RBD epitopes on SARS-CoV-2 spike. Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding. Modeling based on these structures suggested different potentials for inter-spike crosslinking by IgGs on viruses, and characterized IgGs would not be affected by identified SARS-CoV-2 spike mutations. Overall, our studies structurally define a recurrent anti-SARS-CoV-2 antibody class derived from VH3-53/VH3-66 and similarity to a SARS-CoV VH3-30 antibody, providing criteria for evaluating vaccine-elicited antibodies.

KW - COVID-19

KW - ELISA

KW - Fab

KW - IgG

KW - MERS-CoV

KW - SARS-CoV

KW - SARS-CoV-2

KW - convalescent plasma

KW - coronavirus

KW - electron microscopy

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U2 - 10.1016/j.cell.2020.06.025

DO - 10.1016/j.cell.2020.06.025

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C2 - 32645326

AN - SCOPUS:85087716217

SN - 0092-8674

VL - 182

SP - 828-842.e16

JO - Cell

JF - Cell

IS - 4

ER -

Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Abstract

Bibliographical note

Keywords

UN SDGs

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