Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology

Reed, Douglas S.; Lackemeyer, Matthew G.; Garza, Nicole L.; Sullivan, Lawrence J.; Nichols, Donald K.

doi:10.1016/j.micinf.2011.05.002

Cited by 88 publications

(84 citation statements)

References 20 publications

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“…Acquisition and analysis of telemetry data were conducted as previously described (23,28). Briefly, body temperature was recorded every 10 to 15 min using a DataQuest A.R.T.…”

Section: Methodsmentioning

confidence: 99%

Aerosolized Rift Valley Fever Virus Causes Fatal Encephalitis in African Green Monkeys and Common Marmosets

Hartman

Powell

Bethel

et al. 2014

J Virol

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Rift Valley fever (RVF) is a veterinary and human disease in Africa and the Middle East. The causative agent, RVF virus (RVFV), can be naturally transmitted by mosquito, direct contact, or aerosol. We sought to develop a nonhuman primate (NHP) model of severe RVF in humans to better understand the pathogenesis of RVF and to use for evaluation of medical countermeasures. NHP from four different species were exposed to aerosols containing RVFV. Both cynomolgus and rhesus macaques developed mild fevers after inhalation of RVFV, but no other clinical signs were noted and no macaque succumbed to RVFV infection. In contrast, both marmosets and African green monkeys (AGM) proved susceptible to aerosolized RVF virus. Fever onset was earlier with the marmosets and had a biphasic pattern similar to what has been reported in humans. Beginning around day 8 to day 10 postexposure, clinical signs consistent with encephalitis were noted in both AGM and marmosets; animals of both species succumbed between days 9 and 11 postexposure. Marmosets were susceptible to lower doses of RVFV than AGM. Histological examination confirmed viral meningoencephalitis in both species. Hematological analyses indicated a drop in platelet counts in both AGM and marmosets suggestive of thrombosis, as well as leukocytosis that consisted mostly of granulocytes. Both AGM and marmosets would serve as useful models of aerosol infection with RVFV.

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“…Acquisition and analysis of telemetry data were conducted as previously described (23,28). Briefly, body temperature was recorded every 10 to 15 min using a DataQuest A.R.T.…”

Section: Methodsmentioning

confidence: 99%

Aerosolized Rift Valley Fever Virus Causes Fatal Encephalitis in African Green Monkeys and Common Marmosets

Hartman

Powell

Bethel

et al. 2014

J Virol

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“…Animal experiments, including those involving NHPs, have raised concerns about the possibility of Ebola virus transmission through aerosol or droplets, resulting in the development of interstitial pneumonia [77][78][79][80][81][82][83][84][85]. EBOV inclusions have been demonstrated within macrophages in lungs and free particles within alveolar spaces, further supporting the possibility of this route of transmission [43].…”

Section: Droplet and Airborne Transmissionmentioning

confidence: 99%

Ebola Virus Shedding and Transmission: Review of Current Evidence

et al. 2016

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Background. The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.Methods. We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.Findings. Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [ preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

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“…Gold system (Data Sciences International). Using data collected prior to challenge, an autoregressive integrated movingaverage model for each macaque was developed and used to forecast body temperature during the postexposure period (15,(44)(45)(46)(47). Residual temperature changes postexposure were determined by subtracting the predicted temperature from the actual temperature recorded for each point.…”

Section: Ethics Statementmentioning

confidence: 99%

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

Reed

Glass

Bakken

et al. 2014

J Virol

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Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. IMPORTANCE Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV).Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.

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Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology

Cited by 88 publications

References 20 publications

Aerosolized Rift Valley Fever Virus Causes Fatal Encephalitis in African Green Monkeys and Common Marmosets

Aerosolized Rift Valley Fever Virus Causes Fatal Encephalitis in African Green Monkeys and Common Marmosets

Ebola Virus Shedding and Transmission: Review of Current Evidence

Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

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