title: Protective Immunity Elicited by Oral Immunization of Mice withSalmonella entericaSerovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB) Mutants.
abstract: We evaluated the extent of attenuation and immunogenicity of the ΔlppABand ΔlppABΔmsbBmutants ofSalmonella entericaserovar Typhimurium when delivered to mice by the oral route. These mutants were deleted either for the Braun lipoprotein genes (lppAandlppB) or in combination with themsbBgene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and triggered robust innate and adaptive immune responses. Comparable levels of IgG and its isotypes were produced in mice infected with wild-type (WT)S. typhimuriumor its aforementioned mutant strains. The ΔlppABΔmsbBmutant-immunized animals resulted in the production of higher levels of fecal IgA and serum cytokines during later stages of vaccination (adaptive response). A significant production of interleukin-6 from T-cells was also noted in the ΔlppABΔmsbBmutant-immunized mice when compared to that of the ΔlppABmutant. On the other hand, IL-17A production was significantly more in the serum of ΔlppABmutant-immunized mice (innate response) with a stronger splenic T-cell proliferative and tumor-necrosis factor-α production. Based on 2-dimensional gel analysis, alterations in the levels of several proteins were observed in both the mutant strains when compared to that in WTS. typhimuriumand could be associated with the higher immunogenicity of the mutants. Finally, both ΔlppABand ΔlppABΔmsbBmutants provided complete protection to immunized mice against a lethal oral challenge dose of WTS. typhimurium. Thus, these mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Erova
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kirtley
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Fitts
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Duraisamy
authors.initials: D
authors.lastname: Ponnusamy
authors.affiliation: Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center Bastrop, TX, USA.
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Baze
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Jourdan A
authors.initials: JA
authors.lastname: Andersson
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA; Sealy Center for Vaccine Development and World Health Organisation Collaborating Center for Vaccine Research, University of Texas Medical BranchGalveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical BranchGalveston, TX, USA.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Tiner
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Sha
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical BranchGalveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical BranchGalveston, TX, USA; Sealy Center for Vaccine Development and World Health Organisation Collaborating Center for Vaccine Research, University of Texas Medical BranchGalveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical BranchGalveston, TX, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency*; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008074:Lipoproteins / Q000172:deficiency*; D051379:Mice; D012480:Salmonella Infections / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000172:deficiency*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D000123:Acetyltransferases
keywords: 2-dimensional gel electrophoresis and analysis; Salmonella enterica serovar Typhimurium; acetyltransferase (MsbB); braun or murein lipoprotein (Lpp); innate and adaptive immune responses; lipopolysaccharide (LPS); mouse model of salmonellosis; oral live-attenuated vaccine