Anticoli Simona, Dorrucci Maria, Iessi Elisabetta, Zaffina Salvatore, Carsetti Rita, Vonesch Nicoletta, Tomao Paola, Ruggieri Anna
Reference Center for Gender-Specific Medicine, Istituto Superiore di Sanità [Italian National Institute of Health], 00161 Rome, Italy.
Department of Infectious Diseases, Istituto Superiore di Sanità [Italian National Institute of Health], 00161 Rome, Italy.
Int J Mol Sci. 2025 Aug 7;26(15):7636. doi: 10.3390/ijms26157636.
Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies.
基于性别的免疫差异显著影响疫苗接种的结果，然而，支撑这些差异的分子介质在很大程度上仍然难以捉摸。微小RNA（miRNA）作为基因表达的关键转录后调节因子，已成为先天性和适应性免疫反应的关键调节因子。在本研究中，我们调查了一组医护人员中选定的循环miRNA的表达谱，作为对mRNA新冠疫苗性别特异性体液反应的潜在生物标志物。在接种疫苗后的特定时间点（平均71天）纵向采集血浆样本，并使用RT-qPCR进行分析，以量化一组与免疫相关的miRNA。通过化学发光免疫测定法测量抗刺突（抗-S）IgG滴度。我们的结果揭示了miRNA表达动态中的性别依赖性差异，miR-221-3p和miR-148a-3p在接种疫苗的女性医护人员中显著过表达，而miR-155-5p在接种疫苗的男性中过表达。MiR-148a-3p以性别特异性方式与抗-S/RBD（RBD：受体结合域）IgG水平显著相关。对miRNA靶标的生物信息学分析表明，先天性和适应性免疫反应涉及不同的调节网络和途径，这可能是观察到的男性和女性之间免疫激活差异的潜在原因。这些发现支持循环miRNA作为监测和预测性别特异性疫苗诱导免疫反应及提供机制性见解的微创生物标志物的实用性，这些见解可能为量身定制的疫苗接种策略提供参考。
