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

Cell Rep Med. 2022 Jan 24;3(2):100529. doi: 10.1016/j.xcrm.2022.100529. eCollection 2022 Feb 15.


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.

Keywords: B.1.1.529; Omicron; Omicron variant; SARS-CoV-2; antibody; booster dose; live-virus; mRNA vaccines; neutralization assay; vaccine induced immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / immunology*
  • Adult
  • Aged
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • BNT162 Vaccine / immunology*
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • Chlorocebus aethiops
  • Cohort Studies
  • Female
  • Humans
  • Immunization, Secondary / methods
  • Male
  • Middle Aged
  • Mutation
  • Neutralization Tests
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination / methods*
  • Vero Cells
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants