Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
Cell reports - 37(2021), 1 vom: 05. Okt., Seite 109771 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 18.10.2021 Date Revised 18.09.2023 published: Print-Electronic UpdateOf: bioRxiv. 2021 Jan 03;:. - PMID 33442681 Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2021.109771 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331289830 |
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| 100 | 1 | |a Banach, Bailey B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses |
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| 500 | |a Date Completed 18.10.2021 | ||
| 500 | |a Date Revised 18.09.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2021 Jan 03;:. - PMID 33442681 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be ∼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B-cell | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a biotechnology | |
| 650 | 4 | |a immunity | |
| 650 | 4 | |a neutralization | |
| 650 | 4 | |a public antibody | |
| 650 | 4 | |a virology | |
| 650 | 4 | |a yeast display | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
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| 650 | 7 | |a Immunoglobulin Light Chains |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
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| 650 | 7 | |a ACE2 protein, human |2 NLM | |
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| 700 | 1 | |a Cerutti, Gabriele |e verfasserin |4 aut | |
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| 700 | 1 | |a Shen, Chen-Hsiang |e verfasserin |4 aut | |
| 700 | 1 | |a Oliveira De Souza, Matheus |e verfasserin |4 aut | |
| 700 | 1 | |a Katsamba, Phinikoula S |e verfasserin |4 aut | |
| 700 | 1 | |a Tsybovsky, Yaroslav |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Pengfei |e verfasserin |4 aut | |
| 700 | 1 | |a Nair, Manoj S |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Francino-Urdániz, Irene M |e verfasserin |4 aut | |
| 700 | 1 | |a Steiner, Paul J |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiérrez-González, Matías |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a López Acevedo, Sheila N |e verfasserin |4 aut | |
| 700 | 1 | |a Nazzari, Alexandra F |e verfasserin |4 aut | |
| 700 | 1 | |a Wolfe, Jacy R |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Olia, Adam S |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, I-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Tongqing |e verfasserin |4 aut | |
| 700 | 1 | |a Reddem, Eswar R |e verfasserin |4 aut | |
| 700 | 1 | |a Bimela, Jude |e verfasserin |4 aut | |
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| 700 | 1 | |a Laflin, Amy D |e verfasserin |4 aut | |
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