An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses
The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Science translational medicine - 14(2022), 646 vom: 25. Mai, Seite eabn6859 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Lihong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.05.2022 Date Revised 13.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/scitranslmed.abn6859 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339679085 |
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| 100 | 1 | |a Liu, Lihong |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 27.05.2022 | ||
| 500 | |a Date Revised 13.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The devastation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses, suggesting that 10-40 is a promising agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses but also uncovered a distinct antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Immunoglobulin Isotypes |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Iketani, Sho |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yicheng |e verfasserin |4 aut | |
| 700 | 1 | |a Reddem, Eswar R |e verfasserin |4 aut | |
| 700 | 1 | |a Casner, Ryan G |e verfasserin |4 aut | |
| 700 | 1 | |a Nair, Manoj S |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper F-W |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Maple |e verfasserin |4 aut | |
| 700 | 1 | |a Cerutti, Gabriele |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhiteng |e verfasserin |4 aut | |
| 700 | 1 | |a Morano, Nicholas C |e verfasserin |4 aut | |
| 700 | 1 | |a Castagna, Candace D |e verfasserin |4 aut | |
| 700 | 1 | |a Corredor, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Poon, Vincent Kwok-Man |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Chris Chun-Sing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Cunningham, Marcus |e verfasserin |4 aut | |
| 700 | 1 | |a Chavez, Alejandro |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Michael T |e verfasserin |4 aut | |
| 700 | 1 | |a Perlin, David S |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuji, Moriya |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Kwong, Peter D |e verfasserin |4 aut | |
| 700 | 1 | |a Sheng, Zizhang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Shapiro, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, David D |e verfasserin |4 aut | |
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