Epigenetic aging in immune response to HBV vaccine in B cells isolated from health care workers

Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5–10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients. Bisulphite converted DNA from 71 isolated B cell samples were hybridised to the Illumina Infiniun MethylationEPIC BeadChip following manufacture's protocols.

医护人员（Healthcare Workers, HCWs）是乙型肝炎病毒（Hepatitis B Virus, HBV）感染的高风险人群。值得注意的是，约5%~10%的普通人群对HBV疫苗接种无应答。本研究旨在通过检测DNA甲基化（DNA methylation, DNAm）水平，估算不同性别、对HBV疫苗接种呈应答（Responder, R）或无应答（Non-responder, NR）的医护人员外周血B细胞的生物学年龄。本研究采集了年龄介于22~62岁的41名应答者与30名无应答者的B细胞样本，利用全基因组DNA甲基化数据计算一系列生物标志物。研究发现，HBV疫苗接种无应答与表观遗传衰老加速（DNAmAge、AltumAge、DunedinPoAm）相关，并伴随表观遗传漂移。与同组应答者相比，女性无应答者的端粒长度预估水平更高，而C反应蛋白（C-reactive protein, CRP）炎症风险评分更低。总体而言，应答者与无应答者之间的表观遗传差异在女性群体中较男性群体更为显著。本研究证实，多款基于DNA甲基化的衰老时钟及生物标志物与HBV疫苗接种无应答风险升高相关，该关联在女性群体中尤为突出。基于上述结果，本研究提出表观遗传衰老加速可能是疫苗接种无应答的潜在致病机制之一。该研究结论可为优化疫苗接种策略的效果评估提供参考，尤其适用于医护人员与易感人群。本研究按照制造商提供的实验方案，将71份分离得到的B细胞样本的亚硫酸氢盐转化DNA与Illumina Infiniun MethylationEPIC BeadChip芯片进行杂交。