Broad-spectrum humanized monoclonal neutralizing antibody against SARS-CoV-2 variants, including the Omicron variant

针对 SARS-CoV-2 变体(包括 Omicron 变体)的广谱人源化单克隆中和抗体

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作者:Kun Wen, Jian-Piao Cai, Xiaodi Fan, Xiaojuan Zhang, Cuiting Luo, Kai-Ming Tang, Huiping Shuai, Lin-Lei Chen, Ricky Ruiqi Zhang, Jianwen Situ, Hoi-Wah Tsoi, Kun Wang, Jasper Fuk-Woo Chan, Shuofeng Yuan, Kwok-Yung Yuen, Hongwei Zhou, Kelvin Kai-Wang To

Conclusions

Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

Methods

We produced mAbs by using hybridoma cells that generated from mice immunized with spike protein trimer and receptor binding domain (RBD). The panel of mAbs were screened for binding and neutralizing activity against different SARS-CoV-2 variants. The in vivo effectiveness of WKS13 was evaluated in a hamster model.

Results

Out of 960 clones, we identified 18 mAbs that could bind spike protein. Ten of the mAbs could attach to RBD, among which five had neutralizing activity against the ancestral strain and could block the binding between the spike protein and human ACE2. One of these mAbs, WKS13, had broad neutralizing activity against all Variants of Concern (VOCs), including the Omicron variant. Both murine or humanized versions of WKS13 could reduce the lung viral load in hamsters infected with the Delta variant. Conclusions: Our data showed that broad-spectrum high potency mAbs can be produced from immunized mice, which can be used in humans after humanization of the Fc region. Our method represents a versatile and rapid strategy for generating therapeutic mAbs for upcoming novel variants.

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