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Structural basis for broad coronavirus neutralization
by
Hoffstrom, Benjamin G.
, Veesler, David
, Xiong, Xiaoli
, Acton, Oliver J.
, de van der Schueren, Willem
, Walls, Alexandra C.
, Tortorici, M. Alejandra
, Quispe, Joel
, Sauer, Maximilian M.
, Bowen, John E.
, McGuire, Andrew T.
, Homad, Leah
, Bosch, Berend-Jan
, Park, Young-Jun
, Wang, Chunyan
in
101/1
/ 101/28
/ 631/535/1258/1259
/ 631/535/1266
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - metabolism
/ Antibodies, Neutralizing - immunology
/ Antibodies, Neutralizing - metabolism
/ Antibodies, Viral - immunology
/ Antibodies, Viral - metabolism
/ Betacoronavirus - immunology
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Coronaviridae
/ Coronavirus Infections - immunology
/ Coronavirus Infections - prevention & control
/ Coronaviruses
/ COVID-19
/ Cross Reactions
/ Cross-reactivity
/ Crystallography
/ Epitopes
/ Female
/ Glycoproteins
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Membrane Biology
/ Membrane fusion
/ Membranes
/ Mice
/ Monoclonal antibodies
/ Neutralization
/ Protein Binding
/ Protein Structure
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
/ Structural analysis
/ Vaccination
/ Vaccines
/ Viral diseases
/ X-ray crystallography
2021
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Structural basis for broad coronavirus neutralization
by
Hoffstrom, Benjamin G.
, Veesler, David
, Xiong, Xiaoli
, Acton, Oliver J.
, de van der Schueren, Willem
, Walls, Alexandra C.
, Tortorici, M. Alejandra
, Quispe, Joel
, Sauer, Maximilian M.
, Bowen, John E.
, McGuire, Andrew T.
, Homad, Leah
, Bosch, Berend-Jan
, Park, Young-Jun
, Wang, Chunyan
in
101/1
/ 101/28
/ 631/535/1258/1259
/ 631/535/1266
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - metabolism
/ Antibodies, Neutralizing - immunology
/ Antibodies, Neutralizing - metabolism
/ Antibodies, Viral - immunology
/ Antibodies, Viral - metabolism
/ Betacoronavirus - immunology
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Coronaviridae
/ Coronavirus Infections - immunology
/ Coronavirus Infections - prevention & control
/ Coronaviruses
/ COVID-19
/ Cross Reactions
/ Cross-reactivity
/ Crystallography
/ Epitopes
/ Female
/ Glycoproteins
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Membrane Biology
/ Membrane fusion
/ Membranes
/ Mice
/ Monoclonal antibodies
/ Neutralization
/ Protein Binding
/ Protein Structure
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
/ Structural analysis
/ Vaccination
/ Vaccines
/ Viral diseases
/ X-ray crystallography
2021
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Structural basis for broad coronavirus neutralization
by
Hoffstrom, Benjamin G.
, Veesler, David
, Xiong, Xiaoli
, Acton, Oliver J.
, de van der Schueren, Willem
, Walls, Alexandra C.
, Tortorici, M. Alejandra
, Quispe, Joel
, Sauer, Maximilian M.
, Bowen, John E.
, McGuire, Andrew T.
, Homad, Leah
, Bosch, Berend-Jan
, Park, Young-Jun
, Wang, Chunyan
in
101/1
/ 101/28
/ 631/535/1258/1259
/ 631/535/1266
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - metabolism
/ Antibodies, Neutralizing - immunology
/ Antibodies, Neutralizing - metabolism
/ Antibodies, Viral - immunology
/ Antibodies, Viral - metabolism
/ Betacoronavirus - immunology
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Coronaviridae
/ Coronavirus Infections - immunology
/ Coronavirus Infections - prevention & control
/ Coronaviruses
/ COVID-19
/ Cross Reactions
/ Cross-reactivity
/ Crystallography
/ Epitopes
/ Female
/ Glycoproteins
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Membrane Biology
/ Membrane fusion
/ Membranes
/ Mice
/ Monoclonal antibodies
/ Neutralization
/ Protein Binding
/ Protein Structure
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
/ Structural analysis
/ Vaccination
/ Vaccines
/ Viral diseases
/ X-ray crystallography
2021
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Journal Article
Structural basis for broad coronavirus neutralization
2021
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Overview
Three highly pathogenic β-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight β-coronavirus spike glycoproteins, including all five human-infecting β-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with β-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-β-coronavirus vaccine.
Structural characterization of B6, a monoclonal antibody that cross-reacts with eight β-coronavirus spike proteins from three viral lineages, reveals a conserved cryptic epitope that could serve as a target for structure-guided design of a pan-β-coronavirus vaccine.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 101/28
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - metabolism
/ Antibodies, Neutralizing - immunology
/ Antibodies, Neutralizing - metabolism
/ Antibodies, Viral - immunology
/ Antibodies, Viral - metabolism
/ Betacoronavirus - immunology
/ Biomedical and Life Sciences
/ Coronavirus Infections - immunology
/ Coronavirus Infections - prevention & control
/ COVID-19
/ Epitopes
/ Female
/ Humans
/ Mice
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
/ Vaccines
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