Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model
Abstract Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 μg/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 28. Okt. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Imbrechts, Maya [VerfasserIn] |
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| doi: |
10.1101/2021.11.25.470011 |
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| PPN (Katalog-ID): |
XBI033117322 |
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| 520 | |a Abstract Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 μg/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs. | ||
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| 700 | 1 | |a Noppen, Sam |e verfasserin |4 aut | |
| 700 | 1 | |a Hollevoet, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Vercruysse, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Abdelnabi, Rana |e verfasserin |4 aut | |
| 700 | 1 | |a Foo, Caroline |e verfasserin |4 aut | |
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| 700 | 1 | |a Vanhoorelbeke, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Callewaert, Nico |e verfasserin |4 aut | |
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| 700 | 1 | |a Declerck, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Geukens, Nick |e verfasserin |4 aut | |
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