The effect of spike mutations on SARS-CoV-2 neutralization
2021
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 | Katie J. Doores | Marit J. van Gils | Laura E. McCoy
Summary: 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.
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