title: Vaccination with a ΔnorD ΔznuA Brucella abortus mutant confers potent protection against virulent challenge.
abstract: There remains a need for an improved livestock vaccine for brucellosis since conventional vaccines are only ∼70% efficacious, making some vaccinated animals susceptible to Brucella infections. To address this void, a vaccine capable of evoking protective immunity, while still being sufficiently attenuated to produce minimal disease, is sought. In this pursuit, the ΔnorD ΔznuA B. abortus-lacZ (termed as znBAZ) was developed to be devoid of functional norD and znuA B. abortus genes, and to contain the lacZ as a marker gene. The results show that znBAZ is highly attenuated in mouse and human macrophages, and completely cleared from mouse spleens within eight weeks post-vaccination. Producing less splenic inflammation, znBAZ is significantly more protective than the conventional RB51 vaccine by more than four orders of magnitude. Vaccination with znBAZ elicits elevated numbers of IFN-γ+, TNF-α+, and polyfunctional IFN-γ+TNF-α+CD4+and CD8+T cells in contrast to RB51-vaccinated mice, which show reduced numbers of proinflammatory cytokine-producing T cells. These results demonstrate that znBAZ is a highly efficacious vaccine candidate capable of eliciting diverse T cell subsets that confer protection against parenteral challenge with virulent, wild-type B. abortus.
authors.affiliation: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, FL, USA.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, FL, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Clapp
authors.affiliation: Department of Microbiology & Immunology, Montana State University, Bozeman, MT, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Thornburg
authors.affiliation: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, FL, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Hoffman
authors.affiliation: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, FL, USA. Electronic address: pascuald@ufl.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000818:Animals; D002004:Brucella Vaccine / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D002003:Brucella abortus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D002006:Brucellosis / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005798:Genes, Bacterial; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013154:Spleen / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence
chemical_list: D002004:Brucella Vaccine; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D007371:Interferon-gamma
keywords: Attenuation; Brucella abortus; Live vaccine; Mouse; T cells