Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals

J Clin Invest. 2021 Sep 1;131(17):e152379. doi: 10.1172/JCI152379.


Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein-specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1-convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike-specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.

Keywords: Adaptive immunity; COVID-19; Cytokines; Immunology; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BNT162 Vaccine
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19* / blood
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunity, Cellular / drug effects*
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / metabolism
  • Spike Glycoprotein, Coronavirus* / blood
  • Spike Glycoprotein, Coronavirus* / immunology
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism


  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • BNT162 Vaccine