Effect of lymphocyte miRNA expression on influenza vaccine-induced immunity

Alterations of gene expression by miRNAs contribute substantially to genetic regulation and cellular functions. We conducted a comprehensive study in 53 individuals before and after seasonal inactivated influenza vaccine to characterize lymphocyte-specific miRNA expression (in purified B cells, CD4+ T cells, CD8+ T cells, and NK cells) and its effect on influenza vaccine-induced immune outcomes (hemagglutination inhibition antibody titers/HAI, viral neutralizing antibody titers /VNA, and memory B cell ELISPOT). Overall, we observed relatively stable miRNA expression before and after influenza vaccination. Statistical analysis uncovered three baseline miRNAs (miR-150-3p, miR-629-5p, and miR-4443) that were significantly correlated with influenza vaccine-induced immune outcomes in different cell types. Predictive modeling of influenza vaccine-induced HAI/VNA titers identified a set of specific baseline miRNAs in CD4⁺ T cells as factors predictive of antibody responses. A pathway enrichment analysis on the putative target genes revealed several regulated signaling pathways and functions: TGF-β signaling, PI3K-Akt signaling, p53 signaling, MAPK signaling, TNF signaling, and C-type lectin receptor signaling, as well as cell adhesion and adherens junctions, and antiviral host response. In conclusion, our study offers evidence for the role of epigenetic modification (miRNAs) on influenza vaccine-induced immunity. After validation, identified miRNAs may serve as potential biomarkers of immune response after influenza vaccination.