Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

TLDR

Vaccination induces potent neutralizing antibodies against SARS‑CoV‑2, yet surveillance has identified spike‑mutant variants that may evade these responses. The study assessed neutralization potency in 99 BNT162b2 or mRNA‑1273 recipients against pseudoviruses of 10 circulating SARS‑CoV‑2 strains. Five of the ten pseudoviruses, bearing RBD mutations K417N/T, E484K, and N501Y, were highly resistant to neutralization, and cross‑neutralization of B.1.351 was comparable to SARS‑CoV and bat‑derived WIV1‑CoV, indicating that a few mutations can mediate potent escape and underscoring the need for broadly protective interventions.

Abstract

SUMMARY Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.