MedImmune, Translational Sciences, Gaithersburg, MD 20878, USA.
Vaccine. 2010 Apr 1;28(16):2865-76. doi: 10.1016/j.vaccine.2010.01.060. Epub 2010 Feb 12.
The protective mechanisms of influenza vaccines in young children are not completely understood. A phase 2 clinical study was conducted in 85 children 12-35 months of age to describe and compare the immune responses to live attenuated influenza vaccine (LAIV) with trivalent inactivated influenza vaccine (TIV). To better understand the biology of vaccine effects, oligonucleotide microarrays were employed to measure the genome-wide changes in transcript profiles in whole blood at approximately 7 days after 1 dose of LAIV or TIV. Of the total 265 differentially expressed genes identified in this study, 6 clusters of genes were identified to be tightly coexpressed, many of which are likely modulated by cytokines including type 1 interferons (IFNs) and granulocyte-macrophage colony-stimulating factor. Additional functional analyses revealed that the type 1 IFN pathway and cell cycle regulation-related genes are enriched in the 6 coexpressed gene sets. Promoter characterization of these coexpressed genes also supported this conclusion. Moreover, it is suggested that the IFN-stimulated response element is likely to be a potential bidirectional promoter, and the CCAAT/enhancer-binding protein might cooperate with the E2F transcription factor family in the regulation of the cell cycle in the early immune response induced by the influenza vaccine. Overall, our study clearly indicates that the expression profile changes induced by LAIV are significantly different from those induced by TIV. These results suggest that the pattern of overexpression of type 1 IFN-stimulated genes can potentially be used as a biomarker to identify the early vaccination response of LAIV and may also explain, to a certain extent, previous clinical study observations of LAIV-induced protection against influenza-like illness in the first 2 weeks after administration.
流感疫苗在幼儿中的保护机制尚未完全阐明。一项针对 85 名 12-35 月龄儿童的 2 期临床研究旨在描述和比较活减毒流感疫苗（LAIV）和三价灭活流感疫苗（TIV）的免疫反应。为了更好地了解疫苗效果的生物学机制，采用寡核苷酸微阵列技术在接种 LAIV 或 TIV 后约 7 天测量全血转录谱的全基因组变化。在这项研究中，共鉴定出 265 个差异表达基因，其中 6 个基因簇被鉴定为紧密共表达，其中许多基因可能受到细胞因子（包括 I 型干扰素（IFNs）和粒细胞-巨噬细胞集落刺激因子）的调节。额外的功能分析表明，I 型 IFN 途径和细胞周期调控相关基因在这 6 个共表达基因集中富集。这些共表达基因的启动子特征也支持了这一结论。此外，研究表明 IFN 刺激反应元件可能是一个潜在的双向启动子，CCAAT/增强子结合蛋白可能与 E2F 转录因子家族合作，调节流感疫苗诱导的早期免疫反应中的细胞周期。总的来说，我们的研究清楚地表明，LAIV 诱导的表达谱变化与 TIV 诱导的变化明显不同。这些结果表明，I 型 IFN 刺激基因的过度表达模式可能被用作识别 LAIV 早期接种反应的生物标志物，并且在一定程度上可以解释之前关于 LAIV 在接种后 2 周内预防类似流感疾病的临床研究观察结果。
