title: 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.
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Carwyn
authors.initials: C
authors.lastname: Davies
authors.affiliation: Veterinary Laboratory Agency, Weybridge, New Haw, Addlestone KT15 3NB, UK.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nunez
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hibbs
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Flick-Smith
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Eastaugh
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Smither
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Gates
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Petra
authors.initials: P
authors.lastname: Oyston
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Atkins
authors.affiliation: Defence, Science & Technology Laboratory (Dstl), Porton Down, Salisbury SP4 0JQ, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Eley
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000517:prevention & control* / Q000635:transmission*; D022122:Anthrax Vaccines / Q000276:immunology*; D001408:Bacillus anthracis / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D010316:Particle Size
chemical_list: D000336:Aerosols; D022122:Anthrax Vaccines