Abstract
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® mucosal atomization device (LMA® 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.
Highlights
IntroductionEbola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD), commonly referred to as
Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD), commonly referred to asEbola hemorrhagic fever prior to the 2014–2016 western Africa outbreak [1]
To determine if delivery via the LMA® MAD affected EBOV infectivity, virus was diluted in minimum essential media (MEM) and loaded into a 1 mL syringe
Summary
Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD), commonly referred to as. Ebola hemorrhagic fever prior to the 2014–2016 western Africa outbreak [1]. There are no licensed countermeasures for filovirus infection and the western Africa outbreak emphasizes the urgency for vaccines and therapeutics [1]. Disease modeling and pathogenesis studies rely heavily on well-characterized animal models. As determination of filovirus-countermeasure efficacy in humans is unfeasible and unethical, the US Food and Drug Administration may employ the Animal Efficacy Rule (21 CFR 314.600 and 601.90). To license countermeasures relying on animal efficacy data. The development and testing of effective countermeasures against EBOV will require the development of well-characterized animal models and a thorough understanding of those models.
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