Anti-SARS-CoV-2 cellular immunity in 571 vaccinees assessed using an interferon-γ release assay

Generation of antigen-specific memory T cells has been analyzed only for few coronavirus disease 2019 (COVID-19) vaccinees, whereas antibody titers have been serologically measured for a large number of individuals. Here, we assessed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular immune response in a large cohort using interferon (IFN)-γ release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals who received the viral spike (S) protein-expressing BNT162b2 mRNA SARS-CoV-2 vaccine. Serum IgG titers against the receptor-binding domain (RBD) of S protein were measured. Samples of 28 vaccinees were subjected to flow cytometry analysis of T cells derived from short-term whole blood culture. IFN-γ production triggered by S antigens was observed in most individuals 8 weeks after receiving the second dose of the vaccine, indicating acquisition of T cell memory responses. The frequencies of activated T cell subsets were strongly correlated with IFN-γ levels, supporting the usability of our approach. S antigen-stimulated IFN-γ levels were weakly correlated with anti-RBD IgG titers and associated with pre-vaccination infection and adverse reactions after the second dose. Our approach revealed cellular immunity acquired after COVID-19 vaccination, providing insights regarding the effects and adverse reactions of vaccination.