Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein
Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines..
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Preprint| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 20. Mai Zur Gesamtaufnahme - year:2020 |
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| Sprache: |
Englisch |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2020.05.15.096511 |
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| PPN (Katalog-ID): |
XBI017917654 |
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| 245 | 1 | 0 | |a Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein |
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| 520 | |a Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines. | ||
| 700 | 1 | |a Wrapp, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Herbert, Andrew S. |e verfasserin |4 aut | |
| 700 | 1 | |a Maurer, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Haslwanter, Denise |e verfasserin |4 aut | |
| 700 | 1 | |a Sakharkar, Mrunal |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Rohit K. |e verfasserin |4 aut | |
| 700 | 1 | |a Dieterle, M. Eugenia |e verfasserin |4 aut | |
| 700 | 1 | |a Lilov, Asparouh |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Deli |e verfasserin |4 aut | |
| 700 | 1 | |a Tse, Longping V. |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Nicole V. |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Ching-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nianshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Nett, Juergen H. |e verfasserin |4 aut | |
| 700 | 1 | |a Champney, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Burnina, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Sinclair, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Carl |e verfasserin |4 aut | |
| 700 | 1 | |a Pudi, Sarat |e verfasserin |4 aut | |
| 700 | 1 | |a Bortz, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Wirchnianski, Ariel S. |e verfasserin |4 aut | |
| 700 | 1 | |a Laudermilch, Ethan |e verfasserin |4 aut | |
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| 700 | 1 | |a Dye, John M. |e verfasserin |4 aut | |
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