Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies
Neutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. A 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on "up" RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These 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.
| Errataetall: |
UpdateIn: Cell. 2020 Aug 20;182(4):828-842.e16. - PMID 32645326 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 29. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Barnes, Christopher O [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Revised 11.02.2024 published: Electronic UpdateIn: Cell. 2020 Aug 20;182(4):828-842.e16. - PMID 32645326 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.05.28.121533 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311561047 |
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| 245 | 1 | 0 | |a Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies |
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| 500 | |a UpdateIn: Cell. 2020 Aug 20;182(4):828-842.e16. - PMID 32645326 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Neutralizing antibody responses to coronaviruses focus on the trimeric spike, with most against the receptor-binding domain (RBD). Here we characterized polyclonal IgGs and Fabs from COVID-19 convalescent individuals for recognition of coronavirus spikes. Plasma IgGs differed in their degree of focus on RBD epitopes, recognition of SARS-CoV, MERS-CoV, and mild coronaviruses, and how avidity effects contributed to increased binding/neutralization of IgGs over Fabs. Electron microscopy reconstructions of polyclonal plasma Fab-spike complexes showed recognition of both S1A and RBD epitopes. A 3.4Å cryo-EM structure of a neutralizing monoclonal Fab-S complex revealed an epitope that blocks ACE2 receptor-binding on "up" RBDs. Modeling suggested that IgGs targeting these sites have different potentials for inter-spike crosslinking on viruses and would not be greatly affected by identified SARS-CoV-2 spike mutations. These 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 | ||
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| 700 | 1 | |a Huey-Tubman, Kathryn E |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Magnus A G |e verfasserin |4 aut | |
| 700 | 1 | |a Sharaf, Naima G |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffman, Pauline R |e verfasserin |4 aut | |
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| 700 | 1 | |a Cetrulo Lorenzi, Julio C |e verfasserin |4 aut | |
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