Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients.
Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients.
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DOI：
10.4049/jimmunol.182.3.1706
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发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Pinto LA
中科院分区：
文献类型：
--
作者：
García-Piñeres AJ;Hildesheim A;Dodd L;Kemp TJ;Yang J;Fullmer B;Harro C;Lowy DR;Lempicki RA;Pinto LA
人乳头状瘤（HPV）病毒样颗粒（VLP）疫苗最近获得许可。尽管中和抗体滴度被认为是预防感染的主要效应因子，但长期有效性的早期预测因子尚未确定，并且仍然缺乏对疫苗接种的先天性和适应性免疫应答的全面理解。在这里，微阵列被用来比较HPV-16 L1 VLP刺激的PBMC中的基因表达特征，这些PBMC来自接种疫苗前的17名疫苗和4名安慰剂接受者，以及接受第二次免疫后1个月。用单价HPV-16 L1 VLP疫苗接种与VLP刺激的PBMC中参与炎症/防御反应、细胞因子、干扰素和细胞周期途径的基因的调节相关。此外，存在与细胞毒性（GZMB，TNFSF 10）和调节（INDO，CTLA 4）活性相关的探针组的上调。发现细胞周期蛋白d2（CCND 2）和半乳糖凝集素（LGALS 2）与中和抗体滴度的相关性最强。选择22个差异表达的探针组在一个独立的样本集中通过RT-PCR进行确认。与微阵列数据的协议被认为是超过三分之二的这些probesets。在接种前收集的PBMC中观察到HPV-16 L1 VLP上调免疫/防御反应基因，特别是干扰素诱导的基因，其中许多基因在接种后进一步诱导。总之，我们鉴定了HPV-16 L1 VLP疫苗接种诱导的重要先天性和适应性反应相关基因。需要进一步的研究来确定免疫原性和长期保护的基因表达特征，在临床试验中预测长期HPV疫苗接种结果中具有潜在的实用性。
Human papilloma (HPV) virus-like particle (VLP) vaccines were recently licensed. Though neutralizing antibody titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMC from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization. Vaccination with a monovalent HPV-16 L1 VLP vaccine was associated with modulation of genes involved in the inflammatory/defense response, cytokine, interferon and cell cycle pathways in VLP-stimulated PBMC. Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with microarray data was seen for over two-thirds of these probesets. Up-regulation of immune/defense response genes by HPV-16 L1 VLP, in particular interferon-induced genes was observed in PBMC collected prior to vaccination, with many of these genes being further induced following vaccination. In conclusion, we identified important innate and adaptive response related- genes induced by vaccination with HPV-16 L1 VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials.
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