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

Abstract

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 μm particle aerosol was prolonged compared to that from a 1 μm 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 μm or 12 μm 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 μm or 12 μm particle inhalational infections. Lung deposition was significantly greater after inhalation of the 1 μm particle aerosol with pronounced involvement of the mediastinal lymph node. Gastrointestinal involvement was observed only in mice exposed to 12 μm 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 μg recombinant protective antigen vaccine was equally efficacious against B. anthracis infections arising from the inhalation of 1 and 12 μm particle aerosols, providing 73-80% survival under a suboptimum immunization schedule.