A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model
The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 16. Aug. |
| Sprache: |
Englisch |
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| Anmerkungen: |
Date Revised 16.02.2024 published: Electronic UpdateIn: Cell. 2020 Sep 23;:. - PMID 33058755 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.08.15.252320 |
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| PPN (Katalog-ID): |
NLM313917701 |
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| 245 | 1 | 2 | |a A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model |
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| 500 | |a Date Revised 16.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Cell. 2020 Sep 23;:. - PMID 33058755 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 A revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy | ||
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| 700 | 1 | |a Kornau, Hans-Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Sendin, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Max Corman, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hejun |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Nicholas C |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xueyong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chang-Chun D |e verfasserin |4 aut | |
| 700 | 1 | |a Trimpert, Jakob |e verfasserin |4 aut | |
| 700 | 1 | |a Höltje, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Dietert, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Stöffler, Laura |e verfasserin |4 aut | |
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| 700 | 1 | |a van Hoof, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Homeyer, Marie A |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Julius |e verfasserin |4 aut | |
| 700 | 1 | |a Abdelgawad, Azza |e verfasserin |4 aut | |
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| 700 | 1 | |a Li, Lucie Y |e verfasserin |4 aut | |
| 700 | 1 | |a Barthel, Paula Charlotte |e verfasserin |4 aut | |
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