- 作者: Chen-Yi Chiang, Mei-Yu Chen, Chia-Wei Hsu, Chia-Yeh Liu, Yu-Wen Tsai, Hung-Chun Liao, Jia-Ying Yan, Zih-Shiuan Chuang, Hsin-I. Wang, Chien-Hsiung Pan, Chia-Yi Yu, Guann-Yi Yu, Ching-Len Liao, Shih-Jen Liu & Hsin-Wei Chen
- 作者服務機構: 1.Department of Life Sciences, National Tsing Hua University, Hsinchu, 30072, Taiwan 2.Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 406040, Taiwan 3.Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, 307378, Taiwan 4.National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 35053, Taiwan
- 中文摘要:
- 英文摘要:
Background: Calls for the coronavirus to be treated as an endemic illness, such as the fu, are increasing. After achiev‑
ing 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 SARSCoV-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 stand‑
ard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 block‑
ing 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 efects of the best monoclo‑
nal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model.
Results: Several monoclonal antibodies were selected that neutralize diferent 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 afnity 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 identifed neutralizing epitopes
of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in diferent
regions.
Conclusions: Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Mul‑
tiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks. - 中文關鍵字:
- 英文關鍵字: COVID-19, Monoclonal antibody, Neutralization, SARS-CoV-2, Variant