A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Nature communications - 12(2021), 1 vom: 17. März, Seite 1715 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Chunyan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.04.2021 Date Revised 19.09.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-021-21968-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM322883229 |
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| 100 | 1 | |a Wang, Chunyan |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 01.04.2021 | ||
| 500 | |a Date Revised 19.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth | ||
| 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 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Protein Subunits |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 700 | 1 | |a van Haperen, Rien |e verfasserin |4 aut | |
| 700 | 1 | |a Gutiérrez-Álvarez, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wentao |e verfasserin |4 aut | |
| 700 | 1 | |a Okba, Nisreen M A |e verfasserin |4 aut | |
| 700 | 1 | |a Albulescu, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Widjaja, Ivy |e verfasserin |4 aut | |
| 700 | 1 | |a van Dieren, Brenda |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez-Delgado, Raul |e verfasserin |4 aut | |
| 700 | 1 | |a Sola, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Hurdiss, Daniel L |e verfasserin |4 aut | |
| 700 | 1 | |a Daramola, Olalekan |e verfasserin |4 aut | |
| 700 | 1 | |a Grosveld, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a van Kuppeveld, Frank J M |e verfasserin |4 aut | |
| 700 | 1 | |a Haagmans, Bart L |e verfasserin |4 aut | |
| 700 | 1 | |a Enjuanes, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Drabek, Dubravka |e verfasserin |4 aut | |
| 700 | 1 | |a Bosch, Berend-Jan |e verfasserin |4 aut | |
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