title: Mouse models for assessing the cross-protective efficacy of oral non-typhoidal Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent protease lon and other genes.
abstract: In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a single oral immunization with a mutant strain with an insertion of the chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene decreased the number of salmonellae in each tissue sample 5 days after oral challenge with virulent S. Typhimurium at weeks 26 and 54 post-immunization. These data suggested that an oral immunization with the ClpP- or Lon-disrupted S. Typhimurium strain could provide long-term protection against oral challenge with virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella (NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium and S. enterica serovar Enteritidis harbouring stable in-frame markerless deletions of the clpP-lon-sulA (suppressor of lon), lon-sulA or lon-msbB (acyltransferase) genes. Amongst these orally administered vaccine candidates, those with the lon-sulA gene deletion mutants of S. Typhimurium and S. Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis could be a promising cross-protective NTS live vaccine candidate for practical use in humans.
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukiya
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kodama-Akaboshi
authors.affiliation: National Institute of Animal Health, National Agriculture and Food Research Organization, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Eguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D049069:ATP-Dependent Proteases / Q000235:genetics / Q000276:immunology; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000517:prevention & control*; D012477:Salmonella enteritidis / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D017384:Sequence Deletion; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D017931:DNA Primers; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D049069:ATP-Dependent Proteases