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The use of mice lacking type I or both type I and type II interferon responses in research on hemorrhagic fever viruses. Part 2: Vaccine efficacy studies.
Antiviral Research ( IF 7.6 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.antiviral.2019.104702
Marko Zivcec 1 , Christina F Spiropoulou 1 , Jessica R Spengler 1
Affiliation  

For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, agents that cause viral HF in humans, such as Ebola and Lassa virus, do not cause disease in mature immunocompetent mice. In contrast, IFN-deficient mice typically develop severe or fatal disease when inoculated with these agents. The sensitivity of IFN-deficient mice to disease has led to their widespread use in biocontainment laboratories to assess the efficacy of novel vaccines against HF viruses, often without considering whether adaptive immune responses in IFN-deficient mice accurately mirror those in immunocompetent humans. Failure to recognize these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate these questions. The present article reviews the use of IFN-deficient mice for assessing novel vaccines against HF viruses, including Ebola, Lassa, Crimean-Congo hemorrhagic fever and Rift Valley fever viruses. A companion paper examines the general question of how the lack of IFN signaling may affect adaptive immune responses and the outcome of vaccine studies in mice.

中文翻译:

在出血热病毒研究中使用缺乏I型或I型和II型干扰素反应的小鼠。第2部分:疫苗功效研究。

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)反应的实验室小鼠研究导致人类出血热(HF)的高含量病毒。除裂谷热病毒外,在人类中引起病毒性HF的药物,例如埃博拉病毒和拉沙病毒,均不会在具有免疫功能的成熟小鼠中引起疾病​​。相反,用这些试剂接种的IFN缺陷小鼠通常会出现严重或致命的疾病。缺乏IFN的小鼠对疾病的敏感性已导致它们在生物控制实验室中得到广泛使用,以评估针对HF病毒的新型疫苗的功效,而通常没有考虑到缺乏IFN的小鼠中的适应性免疫反应是否能准确反映出免疫能力强的人的免疫反应。无法识别这些问题可能会导致对鼠标实验的预测价值的不当期望。在两篇受邀的文章中,我们研究了这些问题。本文概述了IFN缺陷小鼠在评估针对HF病毒的新型疫苗中的用途,这些疫苗包括埃博拉病毒,Lassa病毒,克里米亚-刚果出血热病毒和裂谷热病毒。随附的论文探讨了有关缺少IFN信号传导可能如何影响适应性免疫反应以及小鼠疫苗研究结果的一般问题。
更新日期:2020-01-23
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