title: Enhanced vaccine antigen delivery by Salmonella using antibiotic-free operator-repressor titration-based plasmid stabilisation compared to chromosomal integration.
abstract: Live attenuated bacteria provide the potential to replace traditional needle-based vaccination with an orally administered vaccine. The heterologous antigen gene is usually transformed as a multi-copy plasmid into the bacterial cell, but plasmids in live bacterial vaccine strains are often unstable, so an alternative approach is to integrate the single-copy antigen gene into the bacterial chromosome. We report a comparison between the chromosomally integrated and the plasmid-borne Bacillus anthracis protective antigen gene in live Salmonella enterica serovar Typhimurium, using the Operator-Repressor Titration (ORT) system to ensure stable plasmid maintenance. These studies demonstrate that the stabilised plasmid approach of gene expression produced greater amounts of antigenic protein, which in turn resulted in higher antibody responses and levels of protection in mice.
authors.affiliation: Cobra Biomanufacturing Plc, The Science Park, Keele, Staffordshire ST5 5SP, UK.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Leckenby
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Spear
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Neeson
authors.forename: E Diane
authors.initials: ED
authors.lastname: Williamson
authors.forename: Rocky M
authors.initials: RM
authors.lastname: Cranenburgh
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
mesh_terms: D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000235:genetics / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D042822:Genomic Instability; D051379:Mice; D010957:Plasmids; D012486:Salmonella typhimurium / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin