The effect of Spike mutations on SARS-CoV-2 neutralization


Cell Reports

Contributing to research themes:

Multiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, B.1.351 and P.1 lineages, it is critical to understand if 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 was dramatically reduced, in contrast, polyclonal antibodies from patients infected in early 2020 remained active against most mutated Spike pseudotypes, however potency was reduced in a minority of samples. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.

Author list:

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, on behalf of the SAFER Investigators, Katie J. Doores, Marit J. van Gils, Laura E. McCoy