Induction of high affinity monoclonal antibodies against SARS-CoV-2 variant infection using a DNA prime-protein boost strategy

被引:5
|
作者
Chiang, Chen-Yi [1 ]
Chen, Mei-Yu [1 ]
Hsu, Chia-Wei [1 ]
Liu, Chia-Yeh [1 ]
Tsai, Yu-Wen [1 ]
Liao, Hung-Chun [1 ,2 ]
Yan, Jia-Ying [1 ]
Chuang, Zih-Shiuan [1 ]
Wang, Hsin-, I [1 ]
Pan, Chien-Hsiung [1 ]
Yu, Chia-Yi [1 ]
Yu, Guann-Yi [1 ]
Liao, Ching-Len [1 ]
Liu, Shih-Jen [1 ,3 ,4 ]
Chen, Hsin-Wei [1 ,3 ,4 ]
机构
[1] Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol, Miaoli 35053, Taiwan
[2] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 30072, Taiwan
[3] China Med Univ, Grad Inst Biomed Sci, Taichung 406040, Taiwan
[4] Kaohsiung Med Univ, Grad Inst Med, Kaohsiung 307378, Taiwan
关键词
COVID-19; Monoclonal antibody; Neutralization; SARS-CoV-2; Variant; CORONAVIRUS; SARS;
D O I
10.1186/s12929-022-00823-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:13
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