The natural route of human infection with many bacterial and viral diseases is via inhalation of droplet nuclei. Therefore, the production of bioaerosols in a controlled laboratory environment is deemed the most relevant route of infection for animal models. These models can be used to study, in a more natural context, the disease pathogenesis, or preclinical evaluation of the protective efficacy of vaccines or therapeutics against the challenge agent. Critical to the success of these animal models is the ability of the pathogenic microorganism to survive the stresses incurred whilst being generated and suspended as an aerosol. The ability of the pathogen to infect is dependent on aerosol droplet size, number of inhaled organisms and infectious dose. A well-characterised aerosol exposure system is critical for preclinical testing and pathogenesis studies. This thesis contains work, in the form of published papers, with a range of pathogens and animal models. These are the culmination of differing strategies to develop, characterise and qualify aerosol exposure systems at high containment, and the performance of preclinical testing and pathogenesis studies. The strategies employed have been instrumental in the approval of a new vaccine for smallpox, post-exposure treatment regimens of anthrax and other diseases in the biodefence arena, and pre-clinical evaluation of vaccines against tuberculosis.
|Date of Award||Jan 2020|
|Supervisor||Graham Mills (Supervisor)|