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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

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.

Published ahead of print on 4 December 2006.

Editor: J. B. Bliska

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