Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B-anthracis


Stokes, MGM; Titball, RW; Neeson, BN; Galen, JE; Walker, NJ; Stagg, AJ; Jenner, DC; Thwaite, JE; Nataro, JP; Baillie, LWJ; Atkins, HS; (2007) Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B-anthracis. Infection and immunity, 75 (4). pp. 1827-1834. ISSN 0019-9567 DOI: 10.1128/IAI.01242-06

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Abstract

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 10(5) 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.

Item Type: Article
Keywords: SPORE CHALLENGE, LIVE, STRAIN, TYPHI, MICE, IMMUNOGENICITY, OPTIMIZATION, IMMUNIZATION, RESPONSES, SUBTILIS, Administration, Oral, Aerosols, Animals, Anthrax, immunology, prevention & control, Anthrax Vaccines, administration & dosage, genetics, immunology, Antigens, Bacterial, biosynthesis, genetics, immunology, Bacillus anthracis, genetics, immunology, Bacterial Toxins, biosynthesis, genetics, immunology, Disease Models, Animal, Female, Genetic Vectors, Humans, Mice, Recombinant Fusion Proteins, administration & dosage, genetics, immunology, Salmonella typhimurium, genetics, growth & development, immunology, Vaccines, Synthetic, administration & dosage, immunology
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Vaccine Centre
PubMed ID: 17145938
Web of Science ID: 245421400034
URI: http://researchonline.lshtm.ac.uk/id/eprint/9717

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