ABSTRACT
The cellular responses to the BNT162b2 vaccine and their correlation with antibody titer and gender determinants are critical to assess. We aimed to evaluate the cellular response kinetics, correlating it with gender and antibody titer.Peripheral Blood Mononuclear Cells (PBMC) were stimulated with SARS-CoV-2 Spike protein, and the IFN-gamma was evaluated by Elispot assay at 5 different timepoints, for up to 9 months after the BNT162b2 vaccine. 107 healthcare workers were divided into 4 age groups: <40 and >40 years for men, based on the gradual decline of testosterone with aging;<48 and >48 years for women based on the decrease of estrogen with menopause. Furthermore, seropositive individuals were analyzed at baseline to avoid confounding factors caused by the previous infection with SARS-CoV-2. We also analyzed pre-pandemic samples as controls to consider the cross-reactivity toward other coronaviruses. Among seronegative at baseline, the T-cell response against Sprotein changed from a median of 2 spot forming cells (SFC)/400.000 PBMC (Interquartile range, IQR, 0-17) before vaccination to a median of 42 (17.5-78.0) after the second dose. Then, it progressively decreased to 13 (0-34) at 6 months after vaccination and 11 (0-31) after 9 months. At all timepoints, the differences were statistically significant compared to baseline values. Moreover, the results obtained after the second dose were significantly higher than those observed at any other time point. Indeed, a significant correlation was observed between T-cell response and anti-S antibody titer (p<0.001), previously analyzed, even if it was weak in magnitude (r=0.314). Natural seropositive showed higher T cell response at baseline than seronegative ones (median: 2 vs. 29, p=0.003), even if there were no significant differences in response at later time points. Our data suggest that T-cell reactiveness is poorly impacted by sex and age, whereas age was significantly associated with anti-S antibody titer. T-cell response declines 9 months later administration, indicating a waning of immune response over time. So, the positive correlation with the antibody titer confirms a linkage between different arms of adaptive responses and potentially converts future vaccinations into a tailored process.