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The effect of spike mutations on SARS-CoV-2 neutralization.

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journal contribution
posted on 31.03.2021, 11:54 by Chloe Rees-Spear, Luke Muir, Sarah A Griffith, Judith Heaney, Yoann Aldon, Jonne L Snitselaar, Peter Thomas, Carl Graham, Jeffrey Seow, Nayung Lee, Annachiara Rosa, Chloe Roustan, Catherine F Houlihan, Rogier W Sanders, Ravindra K Gupta, Peter Cherepanov, Hans J Stauss, Eleni Nastouli, SAFER Investigators, Katie J Doores, Marit J van Gils, Laura E McCoy
Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines show protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, spike. Because new SARS-CoV-2 variants are emerging rapidly, as exemplified by the B.1.1.7, B.1.351, and P.1 lineages, it is critical to understand whether antibody responses induced by infection with the original SARS-CoV-2 virus or current vaccines remain effective. In this study, we evaluate neutralization of a series of mutated spike pseudotypes based on divergence from SARS-CoV and then compare neutralization of the B.1.1.7 spike pseudotype and individual mutations. Spike-specific monoclonal antibody neutralization is reduced dramatically; in contrast, polyclonal antibodies from individuals infected in early 2020 remain active against most mutated spike pseudotypes, but potency is reduced in a minority of samples. This work highlights that changes in SARS-CoV-2 spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their effect on vaccine efficacy.

Funding

Crick (Grant ID: 10015, Grant title: STP Structural Biology) Crick (Grant ID: 10061, Grant title: Cherepanov FC001061)

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