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Pathogenesis of Aerosolized Ebola Virus Variant Makona in Nonhuman Primates
Abhishek N Prasad1,2, Karla A Fenton1,2, Krystle N Agans1,2
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Background:
Highly pathogenic filoviruses such as Ebola virus (EBOV) hold capacity for delivery by artificial aerosols, and thus potential for intentional misuse. Previous studies have shown that high doses of EBOV delivered by small-particle aerosol cause uniform lethality in nonhuman primates (NHPs), whereas only a few small studies have assessed lower doses in NHPs.
Methods:
To further characterize the pathogenesis of EBOV infection via small-particle aerosol, we challenged cohorts of cynomolgus monkeys with low doses of EBOV variant Makona, which may help define risks associated with small particle aerosol exposures.
Results:
Despite using challenge doses orders of magnitude lower than previous studies, infection via this route was uniformly lethal across all cohorts. Time to death was delayed in a dose-dependent manner between aerosol-challenged cohorts, as well as in comparison to animals challenged via the intramuscular route. Here, we describe the observed clinical and pathological details including serum biomarkers, viral burden, and histopathological changes leading to death.
Conclusions:
Our observations in this model highlight the striking susceptibility of NHPs, and likely humans, via small-particle aerosol exposure to EBOV and emphasize the need for further development of diagnostics and postexposure prophylactics in the event of intentional release via deployment of an aerosol-producing device.
Insights
Even low doses of aerosolized Ebola virus (EBOV) are uniformly lethal in nonhuman primates, with survival time dependent on dose. This highlights the significant risk of aerosolized EBOV exposure.
Area of Science:
- Virology
- Infectious Diseases
- Public Health
Background:
- Highly pathogenic filoviruses like Ebola virus (EBOV) can be aerosolized, posing a risk of intentional misuse.
- Previous research indicated uniform lethality of high-dose aerosolized EBOV in nonhuman primates (NHPs), but low-dose effects were less understood.
Purpose of the Study:
- To characterize the pathogenesis of EBOV infection following small-particle aerosol exposure using low doses.
- To define the risks associated with low-dose aerosolized EBOV exposures.
Main Methods:
- Cohorts of cynomolgus monkeys were challenged with low doses of EBOV variant Makona via small-particle aerosol.
- Clinical signs, serum biomarkers, viral load, and histopathological changes were monitored.
Main Results:
- Infection via aerosol was uniformly lethal across all tested low doses, even at doses orders of magnitude lower than previously studied.
- Time to death showed a dose-dependent delay in aerosol-challenged groups compared to each other and to intramuscularly challenged animals.
Conclusions:
- NHPs, and likely humans, exhibit striking susceptibility to aerosolized EBOV, even at low doses.
- These findings underscore the urgent need for improved diagnostics and postexposure prophylactics against aerosolized EBOV, especially in scenarios of intentional release.
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