Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status

Cell Host Microbe. 2022 Mar 9;30(3):388-399.e3. doi: 10.1016/j.chom.2022.02.003. Epub 2022 Feb 8.


Both SARS-CoV-2 infections and COVID-19 vaccines elicit memory T cell responses. Here, we report the development of 2 pools of experimentally defined SARS-CoV-2 T cell epitopes that, in combination with spike, were used to discriminate 4 groups of subjects with different SARS-CoV-2 infection and COVID-19 vaccine status. The overall T cell-based classification accuracy was 89.2% and 88.5% in the experimental and validation cohorts. This scheme was applicable to different mRNA vaccines and different lengths of time post infection/post vaccination and yielded increased accuracy when compared to serological readouts. T cell responses from breakthrough infections were also studied and effectively segregated from vaccine responses, with a combined performance of 86.6% across all 239 subjects from the 5 groups. We anticipate that a T cell-based immunodiagnostic scheme to classify subjects based on their vaccination and natural infection history will be an important tool for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.

Keywords: COVID-19; SARS-CoV-2; T cells; breakthrough infection; epitope; immunodiagnostic tool; vaccination; viruses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Viral
  • COVID-19 Vaccines*
  • COVID-19* / diagnosis
  • Epitopes, T-Lymphocyte
  • Humans
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • Vaccination


  • Antibodies, Viral
  • COVID-19 Vaccines
  • Epitopes, T-Lymphocyte
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2