Li Shuzhao, Sullivan Nicole L, Rouphael Nadine, Yu Tianwei, Banton Sophia, Maddur Mohan S, McCausland Megan, Chiu Christopher, Canniff Jennifer, Dubey Sheri, Liu Ken, Tran ViLinh, Hagan Thomas, Duraisingham Sai, Wieland Andreas, Mehta Aneesh K, Whitaker Jennifer A, Subramaniam Shankar, Jones Dean P, Sette Alessandro, Vora Kalpit, Weinberg Adriana, Mulligan Mark J, Nakaya Helder I, Levin Myron, Ahmed Rafi, Pulendran Bali
Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30303, USA.
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA.
Cell. 2017 May 18;169(5):862-877.e17. doi: 10.1016/j.cell.2017.04.026. Epub 2017 May 11.
Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4 T cells yet limited CD8 T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
带状疱疹（缠腰龙）在免疫功能低下的宿主和老年人中会导致严重发病。虽然有疫苗可用于预防带状疱疹，但其效力会随着年龄增长而下降。为了有助于理解驱动疫苗反应的机制，我们构建了一个多尺度、多因素反应网络（MMRN），用于研究接种减毒活疫苗Zostavax的健康年轻人和老年人的免疫情况。接种疫苗可诱导产生强大的抗原特异性抗体、浆母细胞和CD4 T细胞，但CD8 T细胞和抗病毒反应有限。MMRN揭示了正交数据集（如转录组学和代谢组学特征、细胞群体和细胞因子水平）之间的显著关联，并确定了疫苗免疫的免疫和代谢相关因素。与肌醇磷酸、甘油磷脂和甾醇代谢相关的网络与免疫紧密耦合。至关重要的是，甾醇调节结合蛋白1及其靶点是抗体和T滤泡细胞反应的关键整合因子。我们的方法广泛适用于研究人类免疫，并有助于识别疗效预测指标以及控制疫苗免疫的机制。
