Haralambieva Iana H, Ratishvili Tamar, Goergen Krista M, Grill Diane E, Simon Whitney L, Chen Jun, Ovsyannikova Inna G, Poland Gregory A, Kennedy Richard B
Mayo Clinic Vaccine Research Group, USA.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Vaccine. 2025 May 10;55:127023. doi: 10.1016/j.vaccine.2025.127023. Epub 2025 Mar 23.
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.
微小RNA（miRNA）对基因表达的改变在很大程度上有助于基因调控和细胞功能。我们对53名个体在接种季节性灭活流感疫苗前后进行了一项全面研究，以表征淋巴细胞特异性miRNA表达（在纯化的B细胞、CD4+T细胞、CD8+T细胞和NK细胞中）及其对流感疫苗诱导的免疫结果（血凝抑制抗体滴度/HAI、病毒中和抗体滴度/VNA和记忆B细胞ELISPOT）的影响。总体而言，我们观察到流感疫苗接种前后miRNA表达相对稳定。统计分析发现了三种基线miRNA（miR-150-3p、miR-629-5p和miR-4443），它们与不同细胞类型中流感疫苗诱导的免疫结果显著相关。流感疫苗诱导的HAI/VNA滴度的预测模型确定了CD4 T细胞中的一组特定基线miRNA作为抗体反应的预测因子。对假定靶基因的通路富集分析揭示了几种受调控的信号通路和功能：TGF-β信号通路、PI3K-Akt信号通路、p53信号通路、MAPK信号通路、TNF信号通路和C型凝集素受体信号通路，以及细胞黏附和黏着连接，以及抗病毒宿主反应。总之，我们的研究为表观遗传修饰（miRNA）在流感疫苗诱导的免疫中的作用提供了证据。经过验证后，鉴定出的miRNA可能作为流感疫苗接种后免疫反应的潜在生物标志物。
