Aerosol Infection of Cynomolgus Macaques with Enzootic Strains of Venezuelan Equine Encephalitis Viruses

Abstract

Because Venezuelan equine encephalitis viruses (VEEVs) are infectious by aerosol, they are considered to be a biological-weapons threat. Nonhuman-primate models are needed to evaluate the efficacy of candidate vaccines. In the present study, cynomolgus macaques, after aerosol exposure to either VEEV-IE or VEEV-IIIA, developed fever, viremia, and lymphopenia; the severity of the fever response, viremia, and lymphopenia correlated with the inhaled dose of VEEV. Of the 10 macaques in our study, 7 developed clinical signs indicative of encephalitis, including loss of balance and hypothermia. In the macaque, the enzootic strains used are infectious by aerosol and lead to disease, including clinical encephalitis.

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

“…2.1 system (Data Sciences). Temperature monitoring began 10-14 days preexposure to develop a baseline training period of temperature data to fit an autoregressive integrated moving average (ARIMA) model [15,19]. Forecasted values for the postexposure time periods were based on the training model extrapolated forward in time.…”

“…Therefore, a superior new VEEV vaccine would need to protect against aerosol exposure to virulent viruses of both the epizootic or enzootic varieties of VEEV. Because viruses of the IE variety are genetically the most distinct from the IA/B viruses within subtype I, we selected an established aerosol challenge nonhuman primate model using the VEEV-IE strain, 68U201, to test our vaccines [15].…”

“…Subsequently, the animal was inserted into a Class III biological safety cabinet located inside a biosafety level-3 suite and exposed in a head-only aerosol chamber to a VEEV aerosol created by a Collison nebulizer for 10 min as previously described [15,19]. Samples were collected from the all-glass impinger (AGI) attached to the aerosol chamber and analyzed by plaque assay to determine the inhaled dose of VEEV.…”

“…Previous studies showed that in naive animals exposed by aerosol to VEEV-IE, fever occurred within 36-48 h while viremia and lymphopenia were detectable at 24 h and peaked at 48 h [15]. On the day of challenge, macaques were exposed by aerosol with a dose of ∼1 × 10 8 PFU of virulent VEEV-IE, which is equivalent to 400 (±200) times the median effective dose required to cause disease.…”

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

“…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.…”