Enhanced vaccine antigen delivery by Salmonella using antibiotic-free operator–repressor titration-based plasmid stabilisation compared to chromosomal integration

• Published in: Microbial pathogenesis Vol. 46; no. 4; pp. 201 - 206
• Main Authors: Leckenby, Matthew W., Spear, Abigail M., Neeson, Brendan N., Williamson, E. Diane, Cranenburgh, Rocky M., Atkins, Helen S.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier India Pvt Ltd 01-04-2009; Elsevier
• Subjects: Animals; Anthrax - prevention & control; Anthrax Vaccines - genetics; Anthrax Vaccines - immunology; Antibodies; Antibodies, Bacterial - blood; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Applied microbiology; Bacillus anthracis; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Bacteriology; Biological and medical sciences; Chromosomes; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic Vectors; Genomic Instability; Haemolysin; Integration; Mice; Microbiology; Miscellaneous; Oral administration; Plasmid stabilisation; Plasmids; Protective antigen; protective antigen gene; Salmonella; Salmonella enterica; Salmonella typhimurium - genetics; Survival Analysis; Titration; Vaccination; Vaccine delivery; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Salmonella; Bacillus anthracis; Plasmid stabilisation; Protective antigen; Haemolysin; Vaccine delivery; Microbiology; Vaccine; Bacillaceae; Antigen; Plasmid; Antibiotic; Bacillales; Bacteria; Hemolysin; Enterobacteriaceae; Quantitative analysis
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2009.01.001

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.