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Infection and Immunity, April 2009, p. 1315-1323, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01473-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Richard J. Thomas,1* Daniel Webber,1 Aaron Collinge,1 Anthony J. Stagg,1 Stephen C. Bailey,1 Alejandro Nunez,2 Amanda Gates,1 Pramukh N. Jayasekera,1 Rosa R. Taylor,1 Steve Eley,1 and Richard W. Titball3

Defence Science & Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JQ,1 Veterinary Laboratories Agency, Weybridge, New Haw, Addlestone, Surrey, United Kingdom KT15 3NB,2 School of Biosciences, Geoffrey Pope Building, University of Exeter, Exeter, Devon, United Kingdom EX4 4QU3

Received 2 December 2008/ Returned for modification 22 January 2009/ Accepted 25 January 2009

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-µm-particle aerosols of Y. pestis in the lower and upper respiratory tracts (URTs) of mice are different. The median lethal dose for 12-µm particles was 4.9-fold greater than that for 1-µm particles. The 12-µm-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-µm-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.

* Corresponding author. Mailing address: Defence Science & Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, United Kingdom SP4 0JQ. Phone: (44) 01980 613199. Fax: (44) 01980 613284. E-mail: rjthomas{at}dstl.gov.uk

{triangledown} Published ahead of print on 2 February 2009.

Editor: J. B. Bliska

Infection and Immunity, April 2009, p. 1315-1323, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01473-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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