Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants.

Wang, Lingshu; Zhou, Tongqing; Zhang, Yi; Yang, Eun Sung; Schramm, Chaim A; Shi, Wei; Pegu, Amarendra; Oloniniyi, Olamide K et al. · Science · 2021

basic_science · Level V

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Abstract

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC<sub>50</sub>) 0.3 to 11.1 nanograms per milliliter; IC<sub>80</sub> 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.

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