Crouse Bethany, Robinson Christine, Huseby Kelcher April, Laudenbach Megan, Abrahante Juan E, Pravetoni Marco
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455 USA.
Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55455 USA.
NPJ Vaccines. 2020 Oct 21;5:99. doi: 10.1038/s41541-020-00247-7. eCollection 2020.
Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4 T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.
阿片类药物使用障碍（OUD）影响着全球超过2700万人。抗阿片类疫苗为治疗OUD和预防过量用药提供了一种有前景的策略。本研究利用细胞因子信号的免疫调节来提高疫苗效力，发现阻断白细胞介素-4（IL-4）可提高针对羟考酮和芬太尼的疫苗在雄性和雌性小鼠中的效力。IL-4受体、信号转导和转录激活因子6（STAT6）的基因缺失，或基于抗体的IL-13清除，均未提高疫苗对阿片类药物的效力，提示I型IL-4受体参与其中。阻断IL-4增强疫苗效力与次级淋巴器官生发中心形成改善以及活化CD4 T细胞群体亚群中的选择性转录组特征有关。这些数据表明，IL-4既是抗OUD疫苗效力的药理学靶点，也是潜在生物标志物。
