Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination
Obesity and Sex Affect the Immune Responses to Tick-Borne Encephalitis Booster Vaccination
复制标题
DOI：
10.3389/fimmu.2020.00860
复制
发表时间：
2020-05-27
影响因子：
7.3
通讯作者：
Wiedermann, Ursula
中科院分区：
文献类型：
--
作者：
Garner-Spitzer, Erika;Poellabauer, Eva-Maria;Wiedermann, Ursula
在过去的30年里，肥胖急剧增加，并达到了世界卫生组织的全球流行病的规模。肥胖相关的慢性低水平炎症会导致严重的合并症，并直接影响许多免疫细胞，导致免疫功能障碍和对感染的易感性增加。因此，预防疫苗可预防的疾病至关重要，但肥胖对几种疫苗的反应性尚不清楚。为了评估对蜱传脑炎（TBE）疫苗的反应性，我们对37名肥胖者和36名体重正常的对照组重新接种了经许可的TBE疫苗。在TBE增强前、1周、4周和6个月的血清和外周血单个核细胞（PBMCs）中评估了代谢、激素和免疫特征以及疫苗特异性体液和细胞免疫反应。肥胖成年人的代谢（甘油三酯、胆固醇比率、瘦素、胰岛素）和促炎（c反应蛋白）参数显著增加。他们表现出tbe特异性抗体滴度（d7_d28）的较强初始增加，随后6个月后明显更快地下降，这与高体重指数、瘦素和胰岛素水平相关。与对照组相比，肥胖男性的抗体滴度增加了两倍，这与睾丸激素水平降低有关。肥胖也影响细胞反应：肥胖疫苗接种者的pbmc在抗原刺激下白细胞介素2和干扰素γ水平升高，表明瘦素依赖性促炎T(H)1极化。肥胖人群中总B细胞和初始B细胞的扩增可能解释了最初Ab滴度的增加，而B记忆细胞和血浆母细胞生成的减少可能与Ab的快速下降和有限的滴度维持有关。在T滤泡辅助细胞（Tfh）细胞中，Tfh17亚群显着扩增，特别是在肥胖男性中，我们观察到强烈的初始Ab增加。全身性而非局部的疫苗副作用在肥胖受试者中更常见，这可能是他们低级别促炎状态的结果。综上所述，TBE加强疫苗接种对肥胖个体有效，但Ab下降较快可能导致长期保护作用降低。疫苗应答的性别差异表明肥胖期间内分泌、代谢和免疫系统之间存在复杂的相互作用。疫苗接种后的长期保护作用的进一步研究正在进行中，并且计划对肥胖个体的TBE初次接种进行评估。
Obesity has dramatically increased over the last 30 years and reaches according to World Health Organization dimensions of a global epidemic. The obesity-associated chronic low-level inflammation contributes to severe comorbidities and directly affects many immune cells leading to immune dysfunction and increased susceptibility to infections. Thus, prophylaxis against vaccine-preventable diseases is crucial, yet the responsiveness to several vaccines is unclear under obesity. In order to assess the responsiveness to tick-borne encephalitis (TBE) vaccine, we revaccinated 37 obese individuals and 36 normal-weight controls with a licensed TBE vaccine. Metabolic, hormonal, and immunologic profiles along with vaccine-specific humoral and cellular immune responses were evaluated in sera and peripheral blood mononuclear cells (PBMCs) before, 1 week, 4 weeks, and 6 months after TBE booster. Obese adults had significantly increased metabolic (triglycerides, cholesterol ratios, leptin, insulin) and proinflammatory (C-reactive protein) parameters. They showed stronger initial increase of TBE-specific Ab titers (d7_d28) followed by a significantly faster decline after 6 months, which correlated with high body mass index and leptin and insulin levels. The fold increase of Ab-titer levels was significantly higher in obese compared to control males and linked to reduced testosterone levels. Obesity also affected cellular responses: PBMCs of the obese vaccinees had elevated interleukin 2 and interferon gamma levels upon antigen stimulation, indicating a leptin-dependent proinflammatory T(H)1 polarization. The expansion of total and naive B cells in obese might explain the initial increase of Ab titers, whereas the reduced B-memory cell and plasma blast generation could be related to fast Ab decline with a limited maintenance of titers. Among T follicular helper cell (Tfh) cells, the Tfh17 subset was significantly expanded particularly in obese males, where we observed a strong initial Ab increase. Systemic but not local vaccine side effects were more frequent in obese subjects as a possible consequence of their low-grade proinflammatory state. In summary, TBE booster vaccination was effective in obese individuals, yet the faster Ab decline could result in a reduced long-term protection. The sex-based differences in vaccine responses indicate a complex interplay of the endocrine, metabolic, and immune system during obesity. Further studies on the long-term protection after vaccination are ongoing, and also evaluation of primary vaccination against TBE in obese individuals is planned.