國家衛生研究院 NHRI:Item 3990099045/14340

NHRI > National Institute of Infectious Diseases and Vaccinology > Hsin-Wei Chen > Periodical Articles > Item 3990099045/14340

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14340

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:	[Hsin-Wei Chen] Periodical Articles [Shih-Jen Liu] Periodical Articles [Ching-Len Liao] Periodical Articles [Guann-Yi Yu] Periodical Articles [Chia-Yi Yu] Periodical Articles [Chien-Hsiung Pan] Periodical Articles

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