Early Patterns of Gene Expression Correlate With the Humoral Immune Response to Influenza Vaccination in Humans
Early Patterns of Gene Expression Correlate With the Humoral Immune Response to Influenza Vaccination in Humans
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DOI：
10.1093/infdis/jiq156
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发表时间：
2011-04-01
影响因子：
6.4
通讯作者：
Belmont, John W.
中科院分区：
文献类型：
--
作者：
Bucasas, Kristine L.;Franco, Luis M.;Belmont, John W.
背景每年接种疫苗是预防流感的主要手段。然而，在疫苗应答中存在很大的个体间变异性，疫苗接种后体内发生的细胞事件知之甚少，并且尚未开发用于疫苗应答的适当生物标志物。我们用已获许可的三价流感疫苗对一组健康男性成年人进行免疫接种，并在接种疫苗前后对整体基因表达进行定时评估。我们分析了基因表达模式与疫苗体液免疫应答之间的关系。在免疫后24小时内检测到干扰素信号传导、阳性IL-6调节以及抗原加工和呈递相关基因表达的显著上调。晚期疫苗应答显示出提示蛋白质生物合成和细胞增殖增加的转录模式。综合分析揭示了494个基因的表达特征，包括STAT 1、CD 74和E2 F2，这与抗体反应的强度密切相关。高疫苗应答状态与干扰素信号传导和抗原加工及呈递基因的早期表达增加相关。这些结果突出了系统生物学方法在理解流感疫苗接种后体内发生的分子事件和开发更好的疫苗反应性预测因子方面的作用。
Background. Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed.Methods. We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination.Results. Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature-including STAT1, CD74, and E2F2-which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes.Conclusions. The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness.