title: Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis.
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.
authors.affiliation: Department of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom.
authors.forename: Margaret G M
authors.initials: MG
authors.lastname: Stokes
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Neeson
authors.forename: James E
authors.initials: JE
authors.lastname: Galen
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Walker
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Stagg
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Jenner
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Thwaite
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Leslie W J
authors.initials: LW
authors.lastname: Baillie
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
mesh_terms: D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000336:Aerosols; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C030325:anthrax toxin