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

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

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.