Center for Global Health, Department of Internal Medicine, Center for Global Health, University of New Mexico, Albuquerque, NM, USA.
Center for Global Health, Department of Internal Medicine, Center for Global Health, University of New Mexico, Albuquerque, NM, USA.
Antiviral Res. 2020 Feb;174:104703. doi: 10.1016/j.antiviral.2019.104703. Epub 2020 Jan 10.
For more than 20 years, researchers have used laboratory mice lacking type I or both type I and type II interferon (IFN) responses to study viruses that cause hemorrhagic fever (HF) in humans. Whereas immunocompetent mice do not become ill when infected with Ebola, Lassa, dengue and other HF viruses, IFN-deficient mice typically develop severe or fatal disease when inoculated with these pathogens. The ease of employment of these "mouse models" has led to their extensive use in biocontainment laboratories to assess the efficacy of novel vaccines, often without consideration of whether adaptive immune responses in IFN-deficient mice accurately mirror those in humans. Failure to consider these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate this question. This paper examines how the lack of type I or both type I and type II IFN signaling may affect the development of adaptive immune responses in mice and the outcome of vaccine studies. A second article reviews the published literature on the use of IFN-deficient mice for the assessment of novel vaccines against HF viruses.
20 多年来,研究人员一直使用缺乏 I 型或 I 型和 II 型干扰素(IFN)反应的实验室小鼠来研究导致人类出血热(HF)的病毒。虽然免疫功能正常的小鼠在感染埃博拉、拉萨、登革热和其他 HF 病毒时不会生病,但缺乏 IFN 的小鼠在接种这些病原体时通常会患上严重或致命的疾病。这些“小鼠模型”易于使用,已导致它们在生物安全实验室中广泛用于评估新型疫苗的功效,而通常不考虑 IFN 缺乏小鼠中的适应性免疫反应是否准确反映人类的反应。不考虑这些问题可能会导致对小鼠实验预测价值的不适当期望。在两篇特邀文章中,我们研究了这个问题。本文探讨了缺乏 I 型或 I 型和 II 型 IFN 信号传导如何影响小鼠适应性免疫反应的发展以及疫苗研究的结果。第二篇文章回顾了关于使用 IFN 缺乏小鼠评估新型 HF 病毒疫苗的已发表文献。