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Infection and Immunity, April 2007, p. 1827-1834, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01242-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Oral Administration of a Salmonella enterica-Based Vaccine Expressing Bacillus anthracis Protective Antigen Confers Protection against Aerosolized B. anthracis{triangledown}

Margaret G. M. Stokes,1 Richard W. Titball,1,2 Brendan N. Neeson,1 James E. Galen,3 Nicola J. Walker,1 Anthony J. Stagg,1 Dominic C. Jenner,1 Joanne E. Thwaite,1 James P. Nataro,3 Leslie W. J. Baillie,4 and Helen S. Atkins1*

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom,1 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom,2 Center for Vaccine Development, School of Medicine, University of Maryland, Baltimore, Maryland 21201,3 University of Maryland Biotechnology Institute, University of Maryland, Baltimore, Maryland 212014

Received 4 August 2006/ Returned for modification 20 October 2006/ Accepted 20 November 2006

Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1. To further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced Salmonella enterica serovar Typhimurium expressing full-length PA, PA domains 1 and 4, or PA domain 4 using codon-optimized PA DNA fused to the S. enterica serovar Typhi ClyA and under the control of the ompC promoter. Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 105 CFU of aerosolized B. anthracis STI spores, whereas Salmonella expressing PA domains 1 and 4 provided only 25% protection (two of eight mice), and Salmonella expressing PA domain 4 or a Salmonella-only control afforded no measurable protection. However, a purified recombinant fusion protein of domains 1 and 4 provided 100% protection, and purified recombinant 4 provided protection in three of eight immunized mice. Thus, we demonstrate for the first time the efficacy of an oral S. enterica-based vaccine against aerosolized B. anthracis spores.

* Corresponding author. Mailing address: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom. Phone: 44 (0)1980 614755. Fax: 44 (0)1980 614307. E-mail: hsatkins{at}dstl.gov.uk.

{triangledown} Published ahead of print on 4 December 2006.

Editor: J. B. Bliska

Infection and Immunity, April 2007, p. 1827-1834, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01242-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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