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

Rees-Spear, Chloe; Muir, Luke; Griffith, Sarah A.; Heaney, Judith; Aldon, Yoann; Snitselaar, Jonne L.; Thomas, Peter; Graham, Carl; Seow, Jeffrey; Lee, Nayung; Rosa, Annachiara; Roustan, Chloe; Houlihan, Catherine F.; Sanders, Rogier W.; Gupta, Ravindra K.; Cherepanov, Peter; Stauss, Hans J.; Nastouli, Eleni; Doores, Katie J.; van Gils, Marit J.; McCoy, Laura E.

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.