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

TLDR

SARS‑CoV‑2 vaccines protect by inducing neutralizing antibodies against the spike protein, but the rapid emergence of variants such as B.1.1.7, B.1.351, and P.1 raises concerns about continued antibody effectiveness. The study aims to assess how spike mutations affect neutralization by comparing neutralization of a panel of spike pseudotypes, including B.1.1.7 and individual mutations, to that of the original virus. Researchers generated spike pseudotypes with mutations derived from SARS‑CoV divergence and performed neutralization assays to evaluate antibody responses. Monoclonal antibody neutralization was dramatically reduced, whereas polyclonal sera from early‑2020 infections remained active against most mutated pseudotypes, though potency fell in a minority of samples, underscoring the need for real‑time monitoring of spike changes and vaccine efficacy.

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.