title: Salmonella typhimurium aroA mutants as carriers of the Escherichia coli heat-labile enterotoxin B subunit to the murine secretory and systemic immune systems.
abstract: We investigated the ability of Salmonella typhimurium vaccines to deliver heterologous antigens to the systemic and secretory immune systems of the mouse, while retaining their immunogenicity against salmonellosis. S. typhimurium SL3261, an avirulent aroA mutant, or SL3261 carrying plasmid pBRD026, a pBR322 derivative encoding the gene for Escherichia coli LT-B were used to immunize BALB/c mice orally. Both immunizing strains invaded the mononuclear phagocyte system of the mice, grew slowly until approximately day 14 post-infection, and then were rapidly cleared. No salmonellae were detected in livers, spleens, mesenteric lymph nodes or Peyer's patches by day 42. Mice immunized with either strain and challenged orally with the virulent parent strain, SL1344, several weeks after clearing the immunizing organism, were protected against the lethal S. typhimurium infection. Mice infected with SL3261 (pBRD026) developed substantial levels of IgG and IgA anti-LT-B antibodies 14 days post-infection in both serum and gut samples. The sera neutralized the effects of LT in an in vitro Vero cell assay. Thus, aroA mutants of S. typhimurium can deliver a heterologous antigen from a different enteric pathogen to the murine systemic and secretory immune systems without altering their efficacy against salmonellosis.
authors.affiliation: Department of Molecular Biology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: K J
authors.initials: KJ
authors.lastname: Sweeney
authors.forename: D
authors.initials: D
authors.lastname: O'Callaghan
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
authors.forename: G
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001427:Bacterial Toxins / Q000235:genetics* / Q000276:immunology; D001428:Bacterial Vaccines; D004768:Enterotoxins / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D029968:Escherichia coli Proteins; D005796:Genes; D005798:Genes, Bacterial; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009500:Neutralization Tests; D010957:Plasmids; D012486:Salmonella typhimurium / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D014169:Transformation, Bacterial
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; C027538:heat-labile enterotoxin, E coli