Abstract
The development and testing of new antitubercular vaccines and drugs require the use of experimental animal models that resemble pulmonary tuberculosis in humans. We evaluated the effectiveness of an aerosol exposure system for studying experimental pulmonary tuberculosis in rabbits. The device is a snout-only exposure system with 6-animal capacity that uses an individual facemask for each animal. The system is operated from a single jet Bio Aerosol Nebulizing Generator (BANG). The device is placed inside a laminar flow biosafety enclosure, specifically constructed to contain the exposure system. The entire aerosol unit is located within the Animal BSL-3 facility at the Public Health Research Institute (PHRI). After establishing and validating the technical parameters of operation, rabbits were infected via the respiratory route with the avirulent M. bovis strain Bacille Calmette-Guerin (BCG). A suspension of 5–10×106 CFU/ml resulted in 3.6 log10 organisms deposited in the lungs; these were almost fully cleared by 14 days. Next, rabbits were infected with the same infectious dose of the virulent clinical isolate of M. tuberculosis HN878. The bacillary load in the lung at 14 days reached 5.3 log10 CFU and increased progressively. Large granulomatous lesions, distributed evenly in the lung parenchyma developed. We conclude that the aerosol exposure unit is easy to operate, yields a consistent implantation of mycobacteria in the lungs, is safe for the investigators, and induces disease similar to that observed in humans infected with M. tuberculosis.