Figure 5. SARS-CoV-2 mRNA vaccines generate durable memory T cell responses.

A) Experimental design and B) gating strategy for quantifying the frequency of SARS-CoV-2-specific CD4+ and CD8+ T cells by AIM assay. For CD4+ T cells, antigen specificity was defined based on co-expression of CD40L and CD200. For CD8+ T cells, antigen specificity was defined based on expression of at least 4/5 activation markers. C) Frequencies of AIM+ CD4+ T and D) AIM+ CD8+ T cells over time in PBMC samples from vaccinated individuals. Data were background subtracted using a paired unstimulated control for each timepoint and are represented as a percentage of non-naïve CD4+ or CD8+ T cells. Fractions above plots indicate the number of individuals above their individual baseline at memory timepoints. Decay rates were calculated using a piecewise linear mixed effects model with censoring. Decay rates were similar in SARS-CoV-2 naïve and recovered groups. E) AIM+ CD4+ T cell memory subsets were identified based on surface expression of CD45RA and CD27, followed by CCR7. F) Frequencies of AIM+ CD4+ T cell memory subsets over time. G) Correlation matrix of memory subset skewing at peak (1 month) response with total AIM+ CD4+ T cell durability at 3 and 6 months. Durability was measured as the percent of peak response maintained at memory timepoints for each individual. H) Correlation between percent of EM1 cells at peak response with 6-month durability. I) AIM+ CD4+ T helper subsets were defined based on chemokine receptor expression. J) Frequencies of AIM+ CD4+ T helper subsets over time. Dotted lines indicate the limit of detection for the assay. Statistics were calculated using unpaired non-parametric Wilcoxon test with Holm correction for multiple comparisons. Correlations were calculated using non-parametric Spearman rank correlation.