Differences in aerosolization of Rift Valley fever virus resulting from choice of inhalation exposure chamber: implications for animal challenge studies

Abstract

The aerosol characteristics of Rift Valley fever virus (RVFV) were evaluated to achieve reproducible infection of experimental animals with aerosolized RVFV suitable for animal efficacy studies. Spray factor (SF), the ratio between the concentrations of the aerosolized agent to the agent in the aerosol generator, is used to compare performance differences between aerosol exposures. SF indicates the efficiency of the aerosolization process; a higher SF means a lower nebulizer concentration is needed to achieve a desired inhaled dose. Relative humidity levels as well as the duration of the exposure and choice of exposure chamber all impacted RVFV SF. Differences were also noted between actual and predicted minute volumes for different species of nonhuman primates. While NHP from Old World species (Macaca fascicularis, M. mulatta, Chlorocebus aethiops) generally had a lower actual minute volume than predicted, the actual minute volume for marmosets (Callithrix jacchus) was higher than predicted (150% for marmosets compared with an average of 35% for all other species examined). All of these factors (relative humidity, chamber, duration, and minute volume) impact the ability to reliably and reproducibly deliver a specific dose of aerosolized RVFV. The implications of these findings for future pivotal efficacy studies are discussed.

A vibrating mesh nebulizer as an alternative to the Collison 3-jet nebulizer for infectious disease aerobiology

“…The Aeroneb was placed in line with the secondary/dilution air to push the air into the exposure chamber. Because exposure chamber structure and volume can influence aerosol performance (5), four exposure chambers were used for these experiments: the rodent nose-only tower (NOT), the rodent whole-body chamber (RWB), the ferret whole-body chamber (FWB), and the nonhuman primate head only chamber (NHP HO), with chamber volumes of 12L, 39L, 44L, and 32L respectively.…”

“…For VEEV, WEEV, and EEEV aerosols, 1% FCS was also added to the culture media. Aerosol concentration was determined as previously described (3, 5).…”

“…Aerosol performance between nebulizers was compared using SF and aerosol efficiency (AE). SF was determined as previously described (3, 5), the ratio of the aerosol concentration (determined from the AGI) to the starting concentration in the aerosol generator. AE is the ratio of the aerosol concentration to the theoretical maximum aerosol concentration as previously described (18).…”

“…Environmental and situational factors can affect the survival, dose, site of deposition, and virulence of pathogenic agents (1–4). For example, studies have shown that relative humidity inside the chamber can alter aerosolization of bacteria and viruses (3, 5–7). Particle size can affect where a pathogen lands in the respiratory tract, which can have dramatic effects on pathogenesis and virulence (1, 2, 4, 8, 9).…”

Animal Models of Human Viral Diseases

“…Increased viremia and tissue tropism were reported in mice with (smith et al, 2010) increased liver enzymes and lymphopenia observed in sick mice. Aerosolized rVFV causes faster and more severe neuropathy in mice compared to the parental route (Dodd et al, 2014;reed et al, 2014). The liver is a target organ following aerosol exposure and liver failure results in fatality.…”