A tetravalent bispecific antibody outperforms the combination of its parental antibodies and neutralizes diverse SARS-CoV-2 variants
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
The devastating impact of COVID-19 on global health shows the need to increase our pandemic preparedness. Recombinant therapeutic antibodies were successfully used to treat and protect at-risk patients from COVID-19. However, the currently circulating Omicron subvariants of SARS-CoV-2 are largely resistant to therapeutic antibodies, and novel approaches to generate broadly neutralizing antibodies are urgently needed. Here, we describe a tetravalent bispecific antibody, A7A9 TVB, which actively neutralized many SARS-CoV-2 variants of concern, including early Omicron subvariants. Interestingly, A7A9 TVB neutralized more variants at lower concentration as compared to the combination of its parental monoclonal antibodies, A7K and A9L. A7A9 also reduced the viral load of authentic Omicron BA.1 virus in infected pseudostratified primary human nasal epithelial cells. Overall, A7A9 displayed the characteristics of a potent broadly neutralizing antibody, which may be suitable for prophylactic and therapeutic applications in the clinics, thus highlighting the usefulness of an effective antibody-designing approach.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:260 |
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| Enthalten in: |
Clinical immunology (Orlando, Fla.) - 260(2024) vom: 15. März, Seite 109902 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chiyyeadu, Abhishek [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.clim.2024.109902 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367087596 |
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| 100 | 1 | |a Chiyyeadu, Abhishek |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A tetravalent bispecific antibody outperforms the combination of its parental antibodies and neutralizes diverse SARS-CoV-2 variants |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The devastating impact of COVID-19 on global health shows the need to increase our pandemic preparedness. Recombinant therapeutic antibodies were successfully used to treat and protect at-risk patients from COVID-19. However, the currently circulating Omicron subvariants of SARS-CoV-2 are largely resistant to therapeutic antibodies, and novel approaches to generate broadly neutralizing antibodies are urgently needed. Here, we describe a tetravalent bispecific antibody, A7A9 TVB, which actively neutralized many SARS-CoV-2 variants of concern, including early Omicron subvariants. Interestingly, A7A9 TVB neutralized more variants at lower concentration as compared to the combination of its parental monoclonal antibodies, A7K and A9L. A7A9 also reduced the viral load of authentic Omicron BA.1 virus in infected pseudostratified primary human nasal epithelial cells. Overall, A7A9 displayed the characteristics of a potent broadly neutralizing antibody, which may be suitable for prophylactic and therapeutic applications in the clinics, thus highlighting the usefulness of an effective antibody-designing approach | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a Tetravalent bispecific antibody | |
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| 700 | 1 | |a Asgedom, Girmay |e verfasserin |4 aut | |
| 700 | 1 | |a Bruhn, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Rocha, Cheila |e verfasserin |4 aut | |
| 700 | 1 | |a Schlegel, Tom U |e verfasserin |4 aut | |
| 700 | 1 | |a Neumann, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Galla, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Vollmer Barbosa, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Ehrhardt, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Ha, Teng-Cheong |e verfasserin |4 aut | |
| 700 | 1 | |a Morgan, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Schoeder, Clara T |e verfasserin |4 aut | |
| 700 | 1 | |a Pöhlmann, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Kalinke, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Schambach, Axel |e verfasserin |4 aut | |
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