title: Salmonella Typhimurium lacking the Znuabc transporter is attenuated and immunogenic in pigs.
abstract: Meat contamination by Salmonella spp. is emerging as a major cause of human enteric infections in industrialized countries. The attempts to reduce human cases of salmonellosis encompass pre- and post-harvest interventions. In this context, vaccination of pigs may represent an effective instrument in eliminating/reducing Salmonella burden through the food chain. We have previously demonstrated that Salmonella Typhimurium lacking the ZnuABC transporter (S. Typhimurium ΔznuABC) is a promising candidate live vaccine in different mouse models of Salmonella Typhimurium infection. In this study, we confirmed in pigs the attenuation of S. Typhimurium ΔznuABC. Moreover, we evaluated the safety and immunogenicity of S. Typhimurium ΔznuABC administered to pigs by the oral route. We monitored clinical conditions of animals and we conducted a microbiological culture and a quantification of the humoral and cellular immune response, respectively, on fecal and blood samples of pigs. After vaccination with attenuated S. Typhimurium ΔznuABC, pigs showed a modest degree of hyperthermia. In addition, fecal shedding of S. Typhimurium ΔznuABC could not be detected 28 days after the inoculum. Furthermore, vaccination with S. Typhimurium ΔznuABC elicited a distinct production of anti-Salmonella antibodies and IFN-γ. Taken together, these results suggest that S. Typhimurium ΔznuABC is attenuated and immunogenic in pigs. Although the vaccine dosages do not guarantee complete safety there is ample margin to set up better conditions of use, suggesting that S. Typhimurium ΔznuABC could be a promising attenuated strain to be used as live mucosal vaccine for oral delivery.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pesciaroli
authors.forename: M
authors.initials: M
authors.lastname: Gradassi
authors.forename: N
authors.initials: N
authors.lastname: Martinelli
authors.forename: J
authors.initials: J
authors.lastname: Ruggeri
authors.forename: C
authors.initials: C
authors.lastname: Pistoia
authors.forename: M
authors.initials: M
authors.lastname: Raffatellu
authors.forename: C F
authors.initials: CF
authors.lastname: Magistrali
authors.forename: A
authors.initials: A
authors.lastname: Battistoni
authors.forename: P
authors.initials: P
authors.lastname: Pasquali
authors.forename: G L
authors.initials: GL
authors.lastname: Alborali
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D027682:Cation Transport Proteins / Q000235:genetics*; D005243:Feces / Q000382:microbiology; D005260:Female; D007111:Immunity, Cellular; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D034421:Sus scrofa / Q000276:immunology* / Q000382:microbiology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015032:Zinc
chemical_list: D027682:Cation Transport Proteins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D015032:Zinc