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Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals
Anthony T. Tan, … , David C. Lye, Antonio Bertoletti
Anthony T. Tan, … , David C. Lye, Antonio Bertoletti
Published September 1, 2021
Citation Information: J Clin Invest. 2021;131(17):e152379. https://doi.org/10.1172/JCI152379.
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Research Article Immunology

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

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Abstract

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.

Authors

Anthony T. Tan, Joey M.E. Lim, Nina Le Bert, Kamini Kunasegaran, Adeline Chia, Martin D.C. Qui, Nicole Tan, Wan Ni Chia, Ruklanthi de Alwis, Ding Ying, Jean X.Y. Sim, Eng Eong Ooi, Lin-Fa Wang, Mark I-Cheng Chen, Barnaby E. Young, Li Yang Hsu, Jenny G.H. Low, David C. Lye, Antonio Bertoletti

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Figure 6

Longitudinal quantification of spike-specific T cells from whole blood in vaccinated and infected individuals.

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Longitudinal quantification of spike-specific T cells from whole blood i...
(A) SARS-CoV-2 spike–specific T cell responses in vaccinated individuals (n = 112; 201 samples) and in convalescent asymptomatic (n = 62; 62 samples) and symptomatic (n = 68; 115 samples) COVID-19 patients were longitudinally quantified by measuring IFN-γ secretion in whole blood after SpG peptide pool stimulation. Cross-reactive SARS-CoV-2 spike–specific T cells were also quantified in whole blood from individuals who were infected with SARS-CoV-1 eighteen years ago (n = 12; 12 samples). The responses of individuals before receiving BNT162b2 vaccination are shown for reference. Pie chart shows the number of peptides in the SpG peptide pool that are conserved or unique between SARS-CoV-2 and SARS-CoV-1. The sampling timespan (highlighted in yellow) is shown, and the number of samples analyzed at each time point is indicated in parentheses. Dashed lines denote the detection cutoff for the measured cytokines. D~14, day ~14. (B) Quantities of secreted IFN-γ (red) and IL-2 (blue) in SpG peptide pool–stimulated whole blood from vaccinees and COVID-19 patients sampled 2–3 months after a boost vaccination dose (Vacc.) or viral clearance. The bars indicate the median value for each group, and the dashed lines indicate the detection cutoff for the measured cytokines. Significant differences were analyzed and are displayed as above. (C) Longitudinal dynamics of secreted IFN-γ (red) and IL-2 (blue) in SpG peptide pool–stimulated whole blood from vaccinees and patients with COVID-19. Dashed lines indicate the detection cutoff for the measured cytokines. Significant differences in each group were analyzed by 1-way ANOVA, and the P value (adjusted for multiple comparisons) are shown. NS = P > 0.05. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001.

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