mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant

TLDR

The SARS‑CoV‑2 omicron variant emerged in November 2021 and contains multiple spike mutations. Serum from mRNA‑vaccinated individuals was tested for neutralization against omicron using a live‑virus assay. Neutralizing activity against omicron dropped 30‑fold 2–4 weeks after the primary series, vanished in naïve individuals after six months, remained detectable (though 22‑fold reduced) in recovered subjects, and was restored to >90% neutralization with a 14‑fold reduction after a booster, demonstrating that a third dose is required for robust protection.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. At 2-4 weeks after a primary series of vaccinations, we observe a 30-fold reduction in neutralizing activity against omicron. Six months after the initial two-vaccine doses, sera from naive vaccinated subjects show no neutralizing activity against omicron. In contrast, COVID-19-recovered individuals 6 months after receiving the primary series of vaccinations show a 22-fold reduction, with the majority of the subjects retaining neutralizing antibody responses. In naive individuals following a booster shot (third dose), we observe a 14-fold reduction in neutralizing activity against omicron, and over 90% of subjects show neutralizing activity. These findings show that a third dose is required to provide robust neutralizing antibody responses against the omicron variant.