The effect of spike mutations on SARS-CoV-2 neutralization
Chloe Rees-Spear, Luke Muir, Sarah Griffith, Judith Heaney, Yoann Aldon, Jonne L. Snitselaar, Peter Thomas, Carl Graham, Jeffrey Seow, Nayung Lee, Annachiara Rosa, Chloë Roustan, Catherine Houlihan, Rogier W. Sanders, Ravindra K. Gupta, Peter Cherepanov, Hans J. Stauss, Eleni Nastouli, Katie J. Doores, Marit J. van Gils, Laura E. McCoy
Abstract
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.