Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant
Copyright © 2023 Wen, Cai, Fan, Zhang, Luo, Tang, Shuai, Chen, Zhang, Situ, Tsoi, Wang, Chan, Yuan, Yuen, Zhou and To..
Introduction: Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective.
Methods: We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model.
Results: Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant.
Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Frontiers in cellular and infection microbiology - 13(2023) vom: 15., Seite 1213806 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wen, Kun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.08.2023 Date Revised 11.09.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fcimb.2023.1213806 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361432607 |
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| 100 | 1 | |a Wen, Kun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 31.08.2023 | ||
| 500 | |a Date Revised 11.09.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Wen, Cai, Fan, Zhang, Luo, Tang, Shuai, Chen, Zhang, Situ, Tsoi, Wang, Chan, Yuan, Yuen, Zhou and To. | ||
| 520 | |a Introduction: Therapeutic monoclonal antibodies (mAbs) against the SARS-CoV-2 spike protein have been shown to improve the outcome of severe COVID-19 patients in clinical trials. However, novel variants with spike protein mutations can render many currently available mAbs ineffective | ||
| 520 | |a Methods: We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model | ||
| 520 | |a Results: Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant | ||
| 520 | |a Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a monoclonal antibody | |
| 650 | 4 | |a prophylaxis | |
| 650 | 4 | |a therapeutics | |
| 650 | 4 | |a variants of concern | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 700 | 1 | |a Cai, Jian-Piao |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaojuan |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Cuiting |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Kai-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Huiping |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lin-Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ricky Ruiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Situ, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a Tsoi, Hoi-Wah |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Hongwei |e verfasserin |4 aut | |
| 700 | 1 | |a To, Kelvin Kai-Wang |e verfasserin |4 aut | |
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