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Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy
BACKGROUND: Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved f...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178533/ https://www.ncbi.nlm.nih.gov/pubmed/35681239 http://dx.doi.org/10.1186/s12929-022-00823-0 |
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author | Chiang, Chen-Yi Chen, Mei-Yu Hsu, Chia-Wei Liu, Chia-Yeh Tsai, Yu-Wen Liao, Hung-Chun Yan, Jia-Ying Chuang, Zih-Shiuan Wang, Hsin-I. Pan, Chien-Hsiung Yu, Chia-Yi Yu, Guann-Yi Liao, Ching-Len Liu, Shih-Jen Chen, Hsin-Wei |
author_facet | Chiang, Chen-Yi Chen, Mei-Yu Hsu, Chia-Wei Liu, Chia-Yeh Tsai, Yu-Wen Liao, Hung-Chun Yan, Jia-Ying Chuang, Zih-Shiuan Wang, Hsin-I. Pan, Chien-Hsiung Yu, Chia-Yi Yu, Guann-Yi Liao, Ching-Len Liu, Shih-Jen Chen, Hsin-Wei |
author_sort | Chiang, Chen-Yi |
collection | PubMed |
description | BACKGROUND: Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. METHODS: We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. RESULTS: Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. CONCLUSIONS: Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12929-022-00823-0. |
format | Online Article Text |
id | pubmed-9178533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91785332022-06-09 Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy Chiang, Chen-Yi Chen, Mei-Yu Hsu, Chia-Wei Liu, Chia-Yeh Tsai, Yu-Wen Liao, Hung-Chun Yan, Jia-Ying Chuang, Zih-Shiuan Wang, Hsin-I. Pan, Chien-Hsiung Yu, Chia-Yi Yu, Guann-Yi Liao, Ching-Len Liu, Shih-Jen Chen, Hsin-Wei J Biomed Sci Research BACKGROUND: Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. METHODS: We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. RESULTS: Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. CONCLUSIONS: Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12929-022-00823-0. BioMed Central 2022-06-09 /pmc/articles/PMC9178533/ /pubmed/35681239 http://dx.doi.org/10.1186/s12929-022-00823-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chiang, Chen-Yi Chen, Mei-Yu Hsu, Chia-Wei Liu, Chia-Yeh Tsai, Yu-Wen Liao, Hung-Chun Yan, Jia-Ying Chuang, Zih-Shiuan Wang, Hsin-I. Pan, Chien-Hsiung Yu, Chia-Yi Yu, Guann-Yi Liao, Ching-Len Liu, Shih-Jen Chen, Hsin-Wei Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title_full | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title_fullStr | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title_full_unstemmed | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title_short | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
title_sort | induction of high affinity monoclonal antibodies against sars-cov-2 variant infection using a dna prime-protein boost strategy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178533/ https://www.ncbi.nlm.nih.gov/pubmed/35681239 http://dx.doi.org/10.1186/s12929-022-00823-0 |
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