Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque
Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque
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DOI：
10.3390/v9110319
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发表时间：
2017-11-01
期刊：
影响因子：
4.7
通讯作者：
Griffiths, Anthony
中科院分区：
文献类型：
--
作者：
Alfson, Kendra J.;Avena, Laura E.;Griffiths, Anthony
埃博拉病毒（EBOV）是一种丝状病毒，可引起埃博拉病毒病（EVD）。尽管迫切需要，但尚无针对丝状病毒感染的批准疫苗或疗法。开发和测试针对埃博拉病毒的有效对策需要使用动物模型，并全面了解该模型如何与人类埃博拉病毒病相一致。大多数已发表的研究报告了模拟针刺传播的肠外暴露结果。然而，根据埃博拉病毒病疫情的数据，密切接触感染的体液似乎是埃博拉病毒传播的主要途径之一。因此，需要进一步的工作来开发代表粘膜暴露的模型。为了表征粘膜暴露于 EBOV 的结果，使用 LMA(R) 粘膜雾化装置 (LMA(R) MAD) 通过鼻内 (IN) 途径将食蟹猴暴露于 EBOV。为了进行比较，四种非人类灵长类动物 (NHP) 通过肌内 (IM) 途径暴露于埃博拉病毒。与通过 IM 途径暴露相比，这种 IN 暴露模型均是致命的，并且与死亡时间有统计学上显着的延迟相关。这更接近地反映了在人类感染中观察到的时间范围。 IN 暴露模型为其他模型提供了一种有吸引力的替代方案，因为它可以深入了解通过粘膜表面暴露的后果，并允许通过不同的暴露途径筛选对策。
Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, further work is needed to develop models that represent mucosal exposure. To characterize the outcome of mucosal exposure to EBOV, cynomolgus macaques were exposed to EBOV via intranasal (IN) route using the LMA((R)) mucosal atomization device (LMA((R)) MAD). For comparison, four non-human primates (NHPs) were exposed to EBOV via intramuscular (IM) route. This IN exposure model was uniformly lethal and correlated with a statistically significant delay in time to death when compared to exposure via the IM route. This more closely reflects the timeframes observed in human infections. An IN model of exposure offers an attractive alternative to other models as it can offer insight into the consequences of exposure via a mucosal surface and allows for screening countermeasures via a different exposure route.