TY - JOUR
T1 - Pathogenesis of Aerosolized Ebola Virus Variant Makona in Nonhuman Primates
AU - Prasad, Abhishek N.
AU - Fenton, Karla A.
AU - Agans, Krystle N.
AU - Borisevich, Viktoriya
AU - Woolsey, Courtney
AU - Comer, Jason E.
AU - Dobias, Natalie S.
AU - Peel, Jennifer E.
AU - Deer, Daniel J.
AU - Geisbert, Joan B.
AU - Lawrence, William S.
AU - Cross, Robert W.
AU - Geisbert, Thomas W.
N1 - Publisher Copyright:
© 2023 Oxford University Press. All rights reserved.
PY - 2023/11/15
Y1 - 2023/11/15
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jiad137
DO - 10.1093/infdis/jiad137
M3 - Article
C2 - 37145930
AN - SCOPUS:85177102779
SN - 0022-1899
VL - 228
SP - S604-S616
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
ER -