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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/14340
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| Title: | Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy |
| Authors: | Chiang, CY;Chen, MY;Hsu, CW;Liu, CY;Tsai, YW;Liao, HC;Yan, JY;Chuang, ZS;Wang, HI;Pan, CH;Yu, CY;Yu, GY;Liao, CL;Liu, SJ;Chen, HW |
| Contributors: | National Institute of Infectious Diseases and Vaccinology |
| Abstract: | 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. |
| Date: | 2022-06-09 |
| Relation: | Journal of Biomedical Science. 2022 Jun 9;29:Article number 37. |
| Link to: | http://dx.doi.org/10.1186/s12929-022-00823-0 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000810130900002 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85131711295 |
| Appears in Collections: | [陳信偉] 期刊論文
[劉士任] 期刊論文
[廖經倫] 期刊論文
[余冠儀] 期刊論文
[余佳益] 期刊論文
[潘建雄] 期刊論文
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| PUB35681239.pdf | | 3941Kb | Adobe PDF | 228 | View/Open |
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