(A) PBMCs collected from participants before vaccination (Pre) and approximately 28 days following (Post) the second dose of the BNT162b2 (n = 33) or ChAdOx1-S (n = 13) vaccines were stimulated in vitro with heat-killed Streptococcus pneumoniae (HKSP), heat-killed Staphylococcus aureus (HKSA), resiquimod (R848), heat-killed Candida albicans (HKCA), or LPS for 20 to 22 hours. Cytokine production was quantified via multiplex immunoassay. (B) Shown is log₂ fold-change (median ± 95% CI) in cytokine concentrations (after versus before vaccination). (C) Expression (geometric mean fluorescence intensity [gMFI]) of HLA-DR and CD86 on classical monocytes (before versus after vaccination). (D) Shown is t-distributed stochastic neighbor embedding (t-SNE) analysis of ATAC-Seq data before and after vaccination. (E) Mean chromatin accessibility and (F) representative plots of peaks ± 5 kb of the TSS of selected genes previously shown to have altered accessibility in monocytes following BNT162b2 or BCG vaccination (4, 6). CPM, counts per million. (B, C, and E) Wilcoxon’s log-rank tests (after versus before vaccination). (C) Groups compared via Mann-Whitney U test. **P < 0.01.