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Experimental Therapeutics

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

Nicholas B. Carrigy, Sasha E. Larsen, Valerie Reese, Tiffany Pecor, Melissa Harrison, Philip J. Kuehl, Graham F. Hatfull, Dominic Sauvageau, Susan L. Baldwin, Warren H. Finlay, Rhea N. Coler, Reinhard Vehring
Nicholas B. Carrigy
aDepartment of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada
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Sasha E. Larsen
bInfectious Disease Research Institute, Seattle, Washington, USA
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Valerie Reese
bInfectious Disease Research Institute, Seattle, Washington, USA
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Tiffany Pecor
bInfectious Disease Research Institute, Seattle, Washington, USA
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Melissa Harrison
cDepartment of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada
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Philip J. Kuehl
dLovelace Biomedical, Albuquerque, New Mexico, USA
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Graham F. Hatfull
eDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Dominic Sauvageau
cDepartment of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada
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Susan L. Baldwin
bInfectious Disease Research Institute, Seattle, Washington, USA
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Warren H. Finlay
aDepartment of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada
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Rhea N. Coler
bInfectious Disease Research Institute, Seattle, Washington, USA
fDepartment of Global Health, University of Washington, Seattle, Washington, USA
gPAI Life Sciences, Inc., Seattle, Washington, USA
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Reinhard Vehring
aDepartment of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada
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DOI: 10.1128/AAC.00871-19
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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.

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Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29
Nicholas B. Carrigy, Sasha E. Larsen, Valerie Reese, Tiffany Pecor, Melissa Harrison, Philip J. Kuehl, Graham F. Hatfull, Dominic Sauvageau, Susan L. Baldwin, Warren H. Finlay, Rhea N. Coler, Reinhard Vehring
Antimicrobial Agents and Chemotherapy Nov 2019, 63 (12) e00871-19; DOI: 10.1128/AAC.00871-19

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Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29
Nicholas B. Carrigy, Sasha E. Larsen, Valerie Reese, Tiffany Pecor, Melissa Harrison, Philip J. Kuehl, Graham F. Hatfull, Dominic Sauvageau, Susan L. Baldwin, Warren H. Finlay, Rhea N. Coler, Reinhard Vehring
Antimicrobial Agents and Chemotherapy Nov 2019, 63 (12) e00871-19; DOI: 10.1128/AAC.00871-19
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KEYWORDS

experimental therapeutics
global health
in vivo murine model
nose-only inhalation device
phage prophylaxis
vibrating mesh nebulizer

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