Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination.
Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination.
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DOI：
10.1038/ncomms10369
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发表时间：
2016-01-08
影响因子：
16.6
通讯作者：
Sékaly RP
中科院分区：
文献类型：
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作者：
Fourati S;Cristescu R;Loboda A;Talla A;Filali A;Railkar R;Schaeffer AK;Favre D;Gagnon D;Peretz Y;Wang IM;Beals CR;Casimiro DR;Carayannopoulos LN;Sékaly RP
衰老与疫苗接种反应低下有关，其机制尚不清楚。在这项研究中，未接种过B型肝炎病毒（HBV）的老年人接种了三种疫苗，包括一种抗HBV疫苗。在这里，我们表明，使用转录和细胞计数分析接种疫苗前收集的全血，增强B细胞反应的基因表达增强和记忆B细胞频率较高与HBV疫苗的反应更强。相比之下，较高水平的炎症反应转录物和促炎性先天细胞的频率增加与对该疫苗的较弱反应相关。红细胞数量增加和血液诱导的应答也与对HBV疫苗的应答不良相关。建立了一个基于转录组学的疫苗接种前预测HBV疫苗应答的模型，并在不同的老年人中进行了验证。这种中等准确（曲线下面积<65%）但稳健的特征得到流式细胞术和细胞因子分析的支持。这项研究是第一个确定基线预测因子和HBV疫苗应答机制的研究。 老龄化与疫苗的不良反应有关，但潜在的机制仍不清楚。在这里，作者使用一种基于系统的方法来定义与健康老年人对B型肝炎疫苗接种无反应性相关的疫苗接种前存在的分子特征。
Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve≈65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine. Ageing is associated with poor responses to vaccines but the underlying mechanism remains unclear. Here the authors use a systems-based approach to define molecular signatures present before vaccination that correlate with non-responsiveness to hepatitis B vaccination in healthy, elderly adults.