Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine

Nature. 2021 Sep;597(7875):268-273. doi: 10.1038/s41586-021-03841-4. Epub 2021 Jul 28.


SARS-CoV-2 spike mRNA vaccines1-3 mediate protection from severe disease as early as ten days after prime vaccination3, when neutralizing antibodies are hardly detectable4-6. Vaccine-induced CD8+ T cells may therefore be the main mediators of protection at this early stage7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Here we show on a single-epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion that generated highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared with natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution. Our results indicate that CD8+ T cells are important effector cells, are expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • BNT162 Vaccine
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Vaccines / immunology*
  • Cells, Cultured
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunization, Secondary
  • Immunologic Memory / immunology
  • SARS-CoV-2 / chemistry
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology
  • Time Factors
  • Vaccination*
  • Vaccines, Synthetic / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • mRNA Vaccine
  • spike protein, SARS-CoV-2
  • BNT162 Vaccine