miR-451a levels rather than human papillomavirus vaccine administration is associated with the severity of murine experimental autoimmune encephalomyelitis.

Human papilloma virus (HPV) vaccine is currently the most effective prophylaxis to prevent cervical cancer. However, concerns regarding its potential severe adverse reactions have limited the vaccination rate. HPV vaccines have been determined to contain adjuvants which induce inflammation by the innate immune system and are crucial for triggering adaptive immunity. MicroRNA-451a (miR-451a) is located within circulating extracellular vesicles (EVs) and regulates the innate immune response. In this study, we examined the effect of HPV vaccines and EV miR-451a on murine experimental autoimmune encephalomyelitis (EAE), which is an autoimmune disorder that affects the central nervous system. Although HPV vaccine induced pro-inflammatory cytokine expression and macrophage cell death, it failed to exacerbate mouse EAE, whereas circulating EV miR-451a levels were associated with the severity of EAE. Since miR-451a knockout exhibited only marginal effect on the murine EAE clinical score, our data suggest that miR-451a levels reflect an unknown condition associated with EAE severity. Interestingly, excessive uptake of glucose increased EV miR-451a levels both in vitro and in vivo and also exacerbated mouse EAE. Therefore, environmental factors that increase EV miR-451a levels exacerbate the autoimmune disorder more than the HPV vaccine. These observations provide evidence for the safety of HPV vaccines.

人乳头瘤病毒（HPV）疫苗是目前预防宫颈癌最有效的预防措施。然而，对其潜在严重不良反应的担忧限制了接种率。HPV疫苗已被确定含有佐剂，这些佐剂可通过先天免疫系统诱导炎症，并且对触发适应性免疫至关重要。微小RNA - 451a（miR - 451a）位于循环的细胞外囊泡（EVs）内，可调节先天免疫反应。在本研究中，我们检测了HPV疫苗和细胞外囊泡miR - 451a对小鼠实验性自身免疫性脑脊髓炎（EAE）的影响，EAE是一种影响中枢神经系统的自身免疫性疾病。尽管HPV疫苗诱导了促炎细胞因子表达和巨噬细胞死亡，但它并未加剧小鼠EAE，而循环的细胞外囊泡miR - 451a水平与EAE的严重程度相关。由于miR - 451a基因敲除对小鼠EAE临床评分仅显示出轻微影响，我们的数据表明miR - 451a水平反映了一种与EAE严重程度相关的未知状况。有趣的是，过量摄取葡萄糖在体外和体内均增加了细胞外囊泡miR - 451a水平，并且也加剧了小鼠EAE。因此，增加细胞外囊泡miR - 451a水平的环境因素比HPV疫苗更能加剧自身免疫性疾病。这些观察结果为HPV疫苗的安全性提供了证据。