System vaccinology for the evaluation of influenza vaccine safety by multiplex gene detection of novel biomarkers in a preclinical study and batch release test.
System vaccinology for the evaluation of influenza vaccine safety by multiplex gene detection of novel biomarkers in a preclinical study and batch release test.
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DOI：
10.1371/journal.pone.0101835
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yamaguchi K
中科院分区：
文献类型：
--
作者：
Mizukami T;Momose H;Kuramitsu M;Takizawa K;Araki K;Furuhata K;Ishii KJ;Hamaguchi I;Yamaguchi K
疫苗是预防传染病的有益和普遍的工具。因此，疫苗的安全性在试验的临床前阶段得到了严格的评估，每一批疫苗都必须由国家控制实验室根据各国发布的指南进行测试。尽管疫苗生产平台和方法很多，但用于安全性评估的动物试验到目前为止还没有变化。我们最近开发了一种疫苗安全性评估的系统生物学方法，其中在一项大鼠临床前研究中鉴定了特定的生物标记物，评估了大流行性H5N1流感疫苗的安全性，包括IRF7、Lgals9、Lgalsbp3、Cxcl11、TIMP1、TAP2、Psmb9、Psme1、TapBP、C2、CSF1、Mx2、Zbp1、Ifrd1、Trafd1、Cxcl9、β2m、NPC1、NGFR和IFI47。目前的研究评估了这20个生物标志物是否可以使用多重基因检测系统来评估季节性三价流感疫苗的安全性、批次到批次和制造商到制造商的一致性。当我们评估来自四个不同制造商的流感HA疫苗(HIV)时，生物标记物分析与常规动物使用试验(如异常毒性试验)的结果相关。此外，与常规方法相比，毒性检测的敏感性和差异性更高、更准确。尽管B制造商的HAV引起的体重略有下降，但统计学上没有显著差异，但我们的结果表明，B制造商的HAV3个碱基、TAPBP、LGals9、IRF7和C2基因在大鼠肺组织中的表达与其他受试HAV有显著差异。使用在这项研究中确认的生物标志物，我们预测流感疫苗的批次之间的一致性和安全性在2天内，而传统的安全性测试需要更长的时间。这些生物标志物将促进未来新流感疫苗的开发，并提供机会开发评估批次间一致性和疫苗安全性的体外方法，作为动物试验的替代方案。
Vaccines are beneficial and universal tools to prevent infectious disease. Thus, safety of vaccines is strictly evaluated in the preclinical phase of trials and every vaccine batch must be tested by the National Control Laboratories according to the guidelines published by each country. Despite many vaccine production platforms and methods, animal testing for safety evaluation is unchanged thus far. We recently developed a systems biological approach to vaccine safety evaluation where identification of specific biomarkers in a rat pre-clinical study evaluated the safety of vaccines for pandemic H5N1 influenza including Irf7, Lgals9, Lgalsbp3, Cxcl11, Timp1, Tap2, Psmb9, Psme1, Tapbp, C2, Csf1, Mx2, Zbp1, Ifrd1, Trafd1, Cxcl9, β2m, Npc1, Ngfr and Ifi47. The current study evaluated whether these 20 biomarkers could evaluate the safety, batch-to-batch and manufacturer-to-manufacturer consistency of seasonal trivalent influenza vaccine using a multiplex gene detection system. When we evaluated the influenza HA vaccine (HAv) from four different manufactures, the biomarker analysis correlated to findings from conventional animal use tests, such as abnormal toxicity test. In addition, sensitivity of toxicity detection and differences in HAvs were higher and more accurate than with conventional methods. Despite a slight decrease in body weight caused by HAv from manufacturer B that was not statistically significant, our results suggest that HAv from manufacturer B is significantly different than the other HAvs tested with regard to Lgals3bp, Tapbp, Lgals9, Irf7 and C2 gene expression in rat lungs. Using the biomarkers confirmed in this study, we predicted batch-to-batch consistency and safety of influenza vaccines within 2 days compared with the conventional safety test, which takes longer. These biomarkers will facilitate the future development of new influenza vaccines and provide an opportunity to develop in vitro methods of evaluating batch-to-batch consistency and vaccine safety as an alternative to animal testing.
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影响因子：
5.5
作者：
Brennan, FR;Dougan, G
通讯作者：
Dougan, G
影响因子：
5.5
作者：
Hamaguchi, Isao;Imai, Jun-ichi;Yamaguchi, Kazunari
通讯作者：
Yamaguchi, Kazunari
影响因子：
5.7
作者：
Wang IM;Bett AJ;Cristescu R;Loboda A;ter Meulen J
通讯作者：
ter Meulen J
DOI：
10.1016/s0092-1157(79)80044-x
发表时间：
1979-01-01
期刊：
JOURNAL OF BIOLOGICAL STANDARDIZATION
影响因子：
--
作者：
NICHOLSON, KG;TYRRELL, DAJ;ANDERSON, SG
通讯作者：
ANDERSON, SG
影响因子：
5.5
作者：
Hamaguchi, Isao;Imai, Jun-ichi;Yamaguchi, Kazunari
通讯作者：
Yamaguchi, Kazunari