T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Nature. 2022 Mar;603(7901):488-492. doi: 10.1038/s41586-022-04460-3. Epub 2022 Jan 31.


The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations1,2 that contribute to viral escape from antibody neutralization3-6 and reduce vaccine protection from infection7,8. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (n = 70). Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere9-12.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • COVID-19 Vaccines / immunology
  • Convalescence
  • Cross Reactions / immunology*
  • Hospitalization
  • Humans
  • Immunity, Cellular*
  • Middle Aged
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*
  • T-Lymphocytes / immunology*


  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants