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

Abstract

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.

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Affiliated Institutions

• Brigham and Women's Hospital US
• Massachusetts General Hospital US
• Max Planck Institute for Infection Biology DE
• Dana-Farber Cancer Institute US
• Africa Health Research Institute ZA
• University of KwaZulu-Natal ZA
• Centre for the AIDS Programme of Research in South Africa ZA
• Ragon Institute of MGH, MIT and Harvard US

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