Influence of particle size on the pathology and efficacy of vaccination in a murine model of inhalational anthrax

Deposition of Bacillus anthracis endospores within either the lungs or nasal passages of A/J mice after aerosol exposure was influenced by different particle sized aerosols and resulted in different infection kinetics The infection resulting from the inhalation of endospores within a 12 mu m particle aerosol was prolonged compared to that from a 1 mu m particle aerosol with a mean time-to-death of 161 +/- 16 1 h and 101 6 +/- 10 4 h, respectively Inhalation of endospores within 1 mu m or 12 mu m particle aerosols resulted in a median lethal dose of 2432 and 7656 c f u, respectively Initial involvement of the upper respiratory tract lymph nodes was observed in 75-83% of mice exposed to either the 1 mu m or 12 mu m particle inhalational infections Lung deposition was significantly greater after inhalation of the 1 mu m particle aerosol with pronounced involvement of the mediastinal lymph node Gastrointestinal involvement was observed only in mice exposed to 12 mu m particle aerosols where bacteriological and histopathological analysis indicated primary gastritis (17%), activation of the Peyer's patches (72%) and colonization and necrosis of the mesenteric lymph nodes (67%) Terminal disease was characterized by bacteraemia in both inhalational infections with preferential dissemination to spleen, liver, kidneys and thymus Immunization with 1 mu g recombinant protective antigen vaccine was equally efficacious against B anthracis infections arising from the inhalation of 1 and 12 mu m particle aerosols, providing 73-80 % survival under a suboptimum immunization schedule