Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

ABSTRACT

Globally, more people die annually from tuberculosis than from any other single infectious agent. Unfortunately, there is no commercially available vaccine that is sufficiently effective at preventing the acquisition of pulmonary tuberculosis in adults. In this study, preexposure prophylactic pulmonary delivery of active aerosolized antituberculosis bacteriophage D29 was evaluated as an option for protection against Mycobacterium tuberculosis infection. An average bacteriophage concentration of approximately 1 PFU/alveolus was achieved in the lungs of mice using a nose-only inhalation device optimized with a dose simulation technique and adapted for use with a vibrating mesh nebulizer. Within 30 min of bacteriophage delivery, the mice received either a low dose (∼50 to 100 CFU) or an ultralow dose (∼5 to 10 CFU) of M. tuberculosis H37Rv aerosol to the lungs. A prophylactic effect was observed, with bacteriophage aerosol pretreatment significantly decreasing M. tuberculosis burden in mouse lungs at 24 h and 3 weeks postchallenge (P < 0.05). These novel results indicate that a sufficient dose of nebulized mycobacteriophage aerosol to the lungs may be a valuable intervention to provide extra protection to health care professionals and other individuals at risk of exposure to M. tuberculosis.