Hamaguchi Isao, Imai Jun-ichi, Momose Haruka, Kawamura Mika, Mizukami Takuo, Kato Hiroshi, Naito Seishiro, Maeyama Jun-ichi, Masumi Atsuko, Kuramitsu Madoka, Takizawa Kazuya, Mochizuki Masayo, Ochiai Masaki, Yamamoto Akihiko, Horiuchi Yoshinobu, Nomura Nobuo, Watanabe Shinya, Yamaguchi Kazunari
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
Vaccine. 2007 Apr 30;25(17):3355-64. doi: 10.1016/j.vaccine.2006.12.059. Epub 2007 Jan 16.
Conventional animal tests such as leukocytosis promoting tests have been used for decades to evaluate toxicity of pertussis vaccine. Here, we examined gene expression in relation to the vaccine toxicity using a DNA microarray. Comparison of conventional animal test data with the DNA microarray-based gene expression data revealed a gene expression pattern highly correlated with leukocytosis in animals. Of 10,490 rat genes analyzed, two genes, alpha1-acid-glycoprotein (Agp) and hemopexin (Hpx), were found up-regulated by the toxin administration in a dose-dependent manner (assayed by a quantitative PCR based on the microarray). Variation of the gene expression was very small amongst the test animals, and the results were highly reproducible. These findings suggest that gene expression analysis of vaccine-treated animals can be used as an accurate and simple method of pertussis vaccine safety assessment.
诸如白细胞增多促进试验等传统动物试验已被用于评估百日咳疫苗的毒性数十年。在此，我们使用DNA微阵列研究了与疫苗毒性相关的基因表达。将传统动物试验数据与基于DNA微阵列的基因表达数据进行比较，揭示了一种与动物白细胞增多高度相关的基因表达模式。在分析的10490个大鼠基因中，发现两个基因，即α1-酸性糖蛋白（Agp）和血红素结合蛋白（Hpx），经毒素给药后呈剂量依赖性上调（通过基于微阵列的定量PCR测定）。试验动物之间基因表达的变化非常小，结果具有高度可重复性。这些发现表明，对接受疫苗治疗的动物进行基因表达分析可作为一种准确且简单的百日咳疫苗安全性评估方法。
