Evaluation of the live vaccine efficacy of virulence plasmid-cured, and phoP- or aroA-deficient Salmonella enterica serovar Typhimurium in mice

We evaluated the protective efficacy of 94-kb virulence plasmid-cured, and phoP- or aroA-deficient strains of Salmonella enterica serovar Typhimurium (Delta phoP or Delta aroA S. Typhimurium) as oral vaccine candidates in BALB/c mice. Two weeks after the completion of 3 oral immunizations with 1 x 10(8) colony-forming units (CFU) of virulence plasmid-cured, and Delta phoP or Delta aroA S Typhimurium at 10-day intervals, S. Typhimurium lipopolysaccharide (LPS)-specific mucosal secretory immunoglobulin A (s-IgA) antibody titers were detected in the cecal homogenate, bile and lung lavage fluid, but not in the intestinal lavage fluid. In addition, the increases in S. Typhimurium LPS-specific immunoglobulin G (IgG) and IgA antibody titers in the serum were also observed 2 weeks after completing 3 oral immunizations with virulence plasmid-cured, and Delta phoP or Delta aroA S. Typhimurium. The series of 3 oral immunizations protected the mice against an oral challenge with 5 x 108 CFU of the virulent strain of S. Typhimurium, suggesting that both the virulence plasmid-cured, and Delta phoP and Delta aroA S. Typhimurium strains are promising candidates for safe and effective live S. Typhimurium vaccines.