Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters
Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters
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DOI：
10.1172/jci121309
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发表时间：
2018-08-31
影响因子：
15.9
通讯作者：
Sette, Alessandro
中科院分区：
文献类型：
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作者：
Antunes, Ricardo da Silva;Babor, Mariana;Sette, Alessandro
在20世纪90年代中期，全细胞百日咳（wP）疫苗与局部和全身不良事件相关，促使许多高收入国家用无细胞百日咳（aP）疫苗替代。在过去十年中，仅接种aP疫苗的儿童百日咳发病率有所上升。我们使用激活诱导标记（AIM）试验比较了接种初始剂量wP或aP疫苗的个体对aP增强剂的免疫反应。具体来说，我们在体外检查了百日咳特异性记忆CD4(+) T细胞应答，强调了2/Th2型与1/Th1型和Th17型差异极化作为儿童接种疫苗的功能。值得注意的是，在当代aP增强剂后，来自原始aP的供体细胞(a)与IL-4， IL-5, IL-13， IL-9和tgf - β增加相关，并减少ifn - γ和IL-17的产生，(b)其体外扩增记忆细胞的能力缺陷，以及(c)体外增殖能力较差。这些差异似乎是T细胞特异性的，因为在aP增强后，两组的抗体滴度和浆母细胞都有相当的增加。总之，我们的数据表明，尽管反复使用脱细胞增强剂，但最初接种aP疫苗的成年人与最初接种wP的成年人相比，在T细胞反应的极化和增殖方面存在长期影响和差异。
In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4(+) T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-beta and decreased IFN-gamma and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.