Proportional mouse model for aerosol infection by influenza

Abstract

Aims The aim of this study was to demonstrate a prototype tool for measuring infectivity of an aerosolized human pathogen – influenza A/PR/8/34 (H1N1) virus – using a small‐animal model in the Controlled Aerosol Test System (CATS). Methods and Results Intranasal inoculation of nonadapted H1N1 virus into C57BL, BALB/c and CD‐1 mice caused infection in all three species. Respiratory exposure of CD‐1 mice to the aerosolized virus at graduated doses was accomplished in a modified rodent exposure apparatus. Weight change was recorded for 7 days postexposure, and viral populations in lung tissue homogenates were measured post mortem by DNA amplification (qRT‐PCR), direct fluorescence and microscopic evaluation of cytopathic effect. Plots of weight change and of PCR cycle threshold vs delivered dose were linear to threshold doses of ~40 TCID50 and ~12 TCID50, respectively. Conclusions MID50 for inspired H1N1 aerosols in CD‐1 mice is between 12 and 40 TCID50; proportionality to dose of weight loss and viral populations makes the CD‐1 mouse a useful model for measuring infectivity by inhalation. Significance and Impact of the Study In the CATS, this mouse–virus model provides the first quantitative method to evaluate the ability of respiratory protective technologies to attenuate the infectivity of an inspired pathogenic aerosol.

Hemagglutinin-based polyanhydride nanovaccines against H5N1 influenza elicit protective virus neutralizing titers and cell-mediated immunity

“…34 All vaccinated mice showed significant reduction in virus load upon challenge as compared to the virus load in the saline-administered mice ( Figure 5B). A wide mouse-to-mouse variability in virus load was observed for all vaccine regimens, with no significant differences among the groups in mean virus loads.…”

Aerosol-phase activity of iodine captured from a triiodide resin filter on fine particles containing an infectious virus

“…This paper details experiments designed to take into account the effects of free and captured iodine in the aerosol state, and to follow those effects over time under varied environmental conditions by utilizing an aerosol incubation system downstream of the filter medium, followed by reduction in residual iodine concurrent with collection of the aerosol for quantification of infectious virus. Accurate quantification of the clinical effect of captured iodine on respiratory transmissibility of infection, including possible contribution by sublethal effects of iodine exposure on infectivity, can be achieved only by testing in an animal model (Stone et al 2012;McDonald et al 2012).…”