title: Assessment of attenuated Salmonella typhimurium strains designed as potential carriers of foreign antigens for mucosal localization and immuno-genicity in a rabbit model.
abstract: Neither wild type nor attenuated S. typhimurium strains induced diarrheal illness in rabbits. All strains localized to the Peyer's patch at higher concentrations than in lumenal contents or adjacent ileum. Wild type S. typhimurium C5 induced a typhoid-like illness in rabbits with severe weight loss, bacteremia, persistent splenic colonization, and serum IgG response. Both attenuated strains were disseminated to spleen (day 3) but produced minimal systemic illness. They induced biliary IgA responses greater than the wild type (day 7), but minimal serum IgG responses. Both mutants of S. typhimurium are suitable for further development as live enteric vaccines to carry foreign antigens since they localize to Peyer's patch after oral inoculation, induce biliary antibody, and produce minimal systemic disease. The attenuated strains tested are systemically disseminated. It remains to be determined whether dissemination (determined by a large virulence plasmid) is necessary for the desired mucosal immune response or acceptable for an oral vaccine strain.
authors.affiliation: Walter Reed Army Institute of Research, Washington, D.C. 20307, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Boedeker
authors.forename: H S
authors.initials: HS
authors.lastname: Houng
authors.forename: D
authors.initials: D
authors.lastname: Hone
authors.forename: L Y
authors.initials: LY
authors.lastname: Tseng
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: C
authors.initials: C
authors.lastname: McQueen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D001646:Bile / Q000276:immunology; D003967:Diarrhea / Q000276:immunology / Q000517:prevention & control; D017353:Gene Deletion; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D008954:Models, Biological; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology; D011817:Rabbits; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated