title: Different pathologies but equal levels of responsiveness to the recombinant F1 and V antigen vaccine and ciprofloxacin in a murine model of plague caused by small- and large-particle aerosols.
abstract: Presently there is a significant effort to develop and evaluate vaccines and antibiotics against the potential bioterrorism agent Yersinia pestis. The animal models used to test these countermeasures involve the deposition of small particles within the lung. However, deliberate aerosol release of Y. pestis will generate both small and large inhalable particles. We report in this study that the pathogenesis patterns of plague infections caused by the deposition of 1- and 12-microm-particle aerosols of Y. pestis in the lower and upper respiratory tracts (URTs) of mice are different. The median lethal dose for 12-mum particles was 4.9-fold greater than that for 1-microm particles. The 12-microm-particle infection resulted in the degradation of the nasal mucosa and nasal-associated lymphoid tissue (NALT) plus cervical lymphadenopathy prior to bacteremic dissemination. Lung involvement was limited to secondary pneumonia. In contrast, the 1-microm-particle infection resulted in primary pneumonia; in 40% of mice, the involvement of NALT and cervical lymphadenopathy were observed, indicating entry via both URT lymphoid tissues and lungs. Despite bacterial deposition in the gastrointestinal tract, the involvement of Peyer's patches was not observed in either infection. Although there were major differences in pathogenesis, the recombinant F1 and V antigen vaccine and ciprofloxacin protected against plague infections caused by small- and large-particle aerosols.
authors.affiliation: Defence Science & Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire SP40JQ, United Kingdom. rjthomas@dstl.gov.uk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thomas
authors.forename: Daniel
authors.initials: D
authors.lastname: Webber
authors.forename: Aaron
authors.initials: A
authors.lastname: Collinge
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Stagg
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bailey
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nunez
authors.forename: Amanda
authors.initials: A
authors.lastname: Gates
authors.forename: Pramukh N
authors.initials: PN
authors.lastname: Jayasekera
authors.forename: Rosa R
authors.initials: RR
authors.lastname: Taylor
authors.forename: Steve
authors.initials: S
authors.lastname: Eley
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010930:Plague / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D002939:Ciprofloxacin