In vitro marker gene expression analyses in human peripheral blood mononuclear cells: A tool to assess safety of influenza vaccines in humans
In vitro marker gene expression analyses in human peripheral blood mononuclear cells: A tool to assess safety of influenza vaccines in humans
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DOI：
10.1080/1547691x.2018.1447052
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发表时间：
2018-01
影响因子：
3.3
通讯作者：
E. Sasaki;H. Momose;Yuki Hiradate;K. Ishii;T. Mizukami;I. Hamaguchi
中科院分区：
文献类型：
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作者：
E. Sasaki;H. Momose;Yuki Hiradate;K. Ishii;T. Mizukami;I. Hamaguchi
摘要疫苗接种于从儿童到老年人的健康个体中，因此通过使用临床前和批放行测试，每批疫苗的高水平安全性和质量一致性必须符合所需的质量标准。由于疫苗接种于人体，因此试验方法应考虑人体生物学反应的重演。我们开发了一种新方法，利用小鼠和大鼠模型中的生物标志物基因表达来评估流感疫苗的安全性。已知一些生物标志物基因在人淋巴细胞、巨噬细胞和树突状细胞中表达;因此，我们认为其中一些基因可能是人和小鼠评价流感疫苗安全性的常见生物标志物。在这项研究中，我们使用人外周血单核细胞（PBMC）作为主要的评估工具，以确认潜在的标记基因在人类中的有用性。PBMC中标志物基因表达的分析显示，在毒性参考流感疫苗（RE）刺激的PBMC中，生物标志物基因表达呈剂量相关性增加。虽然一些标记基因在血凝素裂解疫苗刺激的PBMC中显示出表达增加，但它们的表达水平低于来自两个不同供体的PBMC中的RE。许多标记基因的表达与趋化因子的产生相关。标记基因如IRF 7与其他1型干扰素（IFN）相关信号相关，并在CD 304+浆细胞样树突状细胞（pDC）群体中高度表达。这些结果表明，PBMC及其标记基因可能有助于疫苗在人体中的安全性评价。
Abstract Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety. In this study, we used human peripheral blood mononuclear cells (PBMC) as a primary assessment tool to confirm the usefulness of potential marker genes in humans. Analysis of marker gene expression in PBMC revealed biomarker gene expressions were dose-relatedly increased in toxic reference influenza vaccine (RE)-stimulated PBMC. Although some marker genes showed increased expression in hemagglutinin split vaccine-stimulated PBMC, their expression levels were lower than that of RE in PBMC from two different donors. Many marker gene expressions correlated with chemokine production. Marker genes such as IRF7 were associated with other Type 1 interferon (IFN)-associated signals and were highly expressed in the CD304+ plasmacytoid dendritic cell (pDC) population. These results suggest PBMC and their marker genes may be useful for vaccine safety evaluation in humans.