title: Salmonella enterica serovar Typhimurium strain lacking pmrG-HM-D provides excellent protection against salmonellosis in murine typhoid model.
abstract: The superiority of live attenuated vaccines in systemic salmonellosis has been proven over killed and subunit vaccines, because of its ability to induce protective cell mediated immunity by CD8+ T cells. A live attenuated Salmonella enterica serovar Typhimurium vaccine has been developed by systematic site directed deletion of the pmrG-HM-D chromosomal genomic loci. This gene confers involved in antimicrobial peptide resistance and is involved in LPS modification, both of which are the major immune evasive mechanisms in Salmonella. The efficacy of the newly developed strain in inducing protection against mortality after challenge with the virulent wild type Salmonella typhimurium 12023 was evaluated in mice model of typhoid fever. Animals were immunized and then boosted on days 7 and 14. Following challenge with virulent S. typhimurium 12023, organ burden and mortality of vaccinated mice were less compared to non-immunized controls. The vaccine strain also induced elevated CD8+ T cells in the vaccinated mice. This multiple mutant vaccine candidate appears to be safe for use in pregnant mice and provides a model for the development of live vaccine candidates against naturally occurring salmonellosis and typhoid fever.
authors.affiliation: Centre for Infectious Disease Research and Biosafety Laboratories, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Vidya Devi
authors.initials: VD
authors.lastname: Negi
authors.forename: Santanu
authors.initials: S
authors.lastname: Singhamahapatra
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007117:Immunization, Secondary; D008099:Liver / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010581:Peyer's Patches / Q000382:microbiology; D011247:Pregnancy; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C087732:PmrD protein, Salmonella; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated