Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses
© 2022. The Author(s)..
As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature communications - 13(2022), 1 vom: 27. Dez., Seite 7957 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Mingxi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 29.12.2022 Date Revised 03.01.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-022-35642-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM350866287 |
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| 245 | 1 | 0 | |a Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses |
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| 500 | |a Date Revised 03.01.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines | ||
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| 700 | 1 | |a Aw, Zhen Qin |e verfasserin |4 aut | |
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| 700 | 1 | |a Lei, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Qingtai |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Junxian |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yiling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Yi Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Sisi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Senyan |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Jiwan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ruoke |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Jay Zengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuxing |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xuanling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Justin Jang Hann |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinquan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Linqi |e verfasserin |4 aut | |
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