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Infection and Immunity, July 2003, p. 3831-3836, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3831-3836.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Salmonella enterica Serovar Typhimurium Expressing a Chromosomally Integrated Copy of the Bacillus anthracis Protective Antigen Gene Protects Mice against an Anthrax Spore Challenge

Helen S. Garmory,1* Richard W. Titball,1,2 Kate F. Griffin,1 Ulrike Hahn,3 Reinhard Böhm,3 and Wolfgang Beyer3

Defence Science and Technology Laboratory, Salisbury SP4 0JQ,1 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom,2 Institute of Environmental and Animal Hygiene, University of Hohenheim, 70593 Stuttgart, Germany3

Received 16 December 2002/ Returned for modification 13 March 2003/ Accepted 9 April 2003

Protective immunity against infection with Bacillus anthracis is almost entirely based on a response to the protective antigen (PA), the binding moiety for the two other toxin components. We cloned the PA gene into an auxotrophic mutant of Salmonella enterica serovar Typhimurium as a fusion with the signal sequence of the hemolysin (Hly) A gene of Escherichia coli to allow the export of PA via the Hly export system. To stabilize the export cassette, it was also integrated into the chromosome of the live Salmonella carrier. When S. enterica serovar Typhimurium with the chromosomally integrated PA gene was given intravenously to A/J mice, they developed high levels of antibody to PA. These mice were protected against intraperitoneal challenge with 100 or 1,000 50% lethal doses of B. anthracis strain STI. This work contributes to the development of a Salmonella-based orally delivered anthrax vaccine.

* Corresponding author. Mailing address: Defence Science and Technology Laboratory, CBS Porton Down, Salisbury SP4 0JQ, United Kingdom. Phone: 44-1980-614755. Fax: 44-1980-614307. E-mail: hsgarmory{at}dstl.gov.uk.

Editor: A. D. O'Brien

Infection and Immunity, July 2003, p. 3831-3836, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3831-3836.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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