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 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.
Keywords:
COVID-19; ELISA; Fab; IgG; MERS-CoV; SARS-CoV; SARS-CoV-2; convalescent plasma; coronavirus; electron microscopy.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Neutralizing / blood
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Antibodies, Neutralizing / chemistry*
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Antibodies, Neutralizing / isolation & purification
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Antibodies, Viral / immunology
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Antibodies, Viral / isolation & purification
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Betacoronavirus / chemistry*
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Betacoronavirus / immunology
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COVID-19
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COVID-19 Serotherapy
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Coronavirus Infections / blood
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Coronavirus Infections / immunology*
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Coronavirus Infections / therapy
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Cross Reactions
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Cryoelectron Microscopy
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Epitope Mapping
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Epitopes
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Humans
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Immunization, Passive
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Immunoglobulin Fab Fragments / blood
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Immunoglobulin Fab Fragments / chemistry*
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Immunoglobulin Fab Fragments / isolation & purification
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Immunoglobulin Fab Fragments / ultrastructure
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Immunoglobulin G / blood
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Immunoglobulin G / chemistry*
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Immunoglobulin G / isolation & purification
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Immunoglobulin G / ultrastructure
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Middle East Respiratory Syndrome Coronavirus / chemistry
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Middle East Respiratory Syndrome Coronavirus / immunology
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Models, Molecular
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Pandemics
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Pneumonia, Viral / blood
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Pneumonia, Viral / immunology*
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SARS-CoV-2
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Severe acute respiratory syndrome-related coronavirus / chemistry
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Severe acute respiratory syndrome-related coronavirus / immunology
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Spike Glycoprotein, Coronavirus / chemistry*
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Spike Glycoprotein, Coronavirus / immunology
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Epitopes
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Immunoglobulin Fab Fragments
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Immunoglobulin G
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Spike Glycoprotein, Coronavirus
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spike protein, SARS-CoV-2