Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Infect Dis. 2012 Nov 15;206(10):1512-20. doi: 10.1093/infdis/jis546. Epub 2012 Sep 4.
The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection.
We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses.
The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders.
We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.
天花疫苗引起的免疫反应变化的机制尚不清楚，但对于深入了解痘病毒免疫以及保护相关性具有重要意义。
我们评估了 197 名初次接种天花疫苗者的转录信使 RNA 表达变化，这些人代表了体液和细胞免疫反应的极端情况。
20 个差异表达最显著的基因包括肿瘤坏死因子受体超家族成员、干扰素（IFN）基因、趋化因子基因、锌指蛋白基因、核因子和组蛋白（P≤1.06E(-20)，q≤2.64E(-17)）。通路分析确定了 4 个富集通路，其中 CD4+T 细胞 Th17 亚群细胞因子的产生是最重要的通路（P=3.42E(-05)）。当比较高抗体应答者和低抗体应答者时，两个与先天免疫相关的通路（IFN 的抗病毒作用，P=8.95E(-05)；IFN-α/β信号通路，P=2.92E(-04)）被富集（错误发现率，<0.05）。与免疫功能和转录相关的基因（TLR8，P=0.0002；DAPP1，P=0.0003；LAMP3，P=9.96E(-05)；NR4A2，P≤0.0002；EGR3，P=4.52E(-05)）以及其他可能对免疫有影响的基因（LNPEP，P=3.72E(-05)；CAPRIN1，P=0.0001；XRN1，P=0.0001），在高抗体应答者与低抗体应答者之间的表达存在差异。
我们发现了新的和已知的与免疫相关的基因和通路，这些基因和通路可能解释了对天花疫苗接种的免疫反应差异。
