title: Impaired resistance to infection does not increase the virulence of Salmonella htrA live vaccines for mice.
abstract: We have described a new class of live attenuated salmonella vaccines harbouring lesions in htrA, a stress protein gene previously. The virulence and invasiveness of Salmonella htrA mutants was investigated in three models of increased susceptibility to Salmonella infection. These included BALB/c mice, either given sublethal whole body irradiation (350 R) or administered rabbit anti-TNF alpha antiserum, and (CBA/NfemaleXBALB/cmale)F1 male mice which express the xid sex-linked B cell defect of CBA/N mice and are more susceptible to salmonellae than female littermates. Salmonella typhimurium htrA mutants derived from virulent strains, C5046 (C5 htrA::TnphoA) and BRD726 (SL1344 delta htrA) were not more invasive in immunosuppressed mice than in normal controls in the three mouse models of defective immunity. The results indicate that susceptibility to S. typhimurium htrA vaccines derived from virulent parents is not enhanced by conditions of impaired resistance to infection.
authors.affiliation: Department of Pathology, Cambridge, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Strahan
authors.forename: S N
authors.initials: SN
authors.lastname: Chatfield
authors.forename: J
authors.initials: J
authors.lastname: Tite
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D005798:Genes, Bacterial / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology / Q000528:radiation effects; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009154:Mutation; D012475:Salmonella / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D012481:Salmonella Infections, Animal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence; D014916:Whole-Body Irradiation
chemical_list: D001428:Bacterial Vaccines; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated