title: Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine candidates against Johne's disease.
abstract: Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. Johne's disease has a severe economic impact on the dairy industry in the USA and worldwide. In an effort to combat this disease, we screened several transposon mutants that were attenuated in the murine model of paratuberculosis for the potential use as live attenuated vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with mutations of fabG2_2 and umaA1, respectively) were at or below the limit of detection for tissue colonization suggesting their low level persistence and hence safety. Prior to challenge, both candidates induced a M. paratuberculosis-specific IFN-γ, an indication of eliciting cell-mediated immunity. Following challenge with a virulent strain of M. paratuberculosis, the two vaccine candidates significantly reduced bacterial colonization in organs with reduced histological scores compared to control animals. In addition, one of the vaccine candidates (pgs3965) also induced IL-17a, a cytokine associated with protective immunity in mycobacterial infection. Our analysis suggested that the pgs3965 vaccine candidate is a potential live-attenuated vaccine that could be tested further in ruminant models of paratuberculosis. The analysis also validated our screening strategy to identify effective vaccine candidates against intracellular pathogens.
authors.affiliation: Pan Genome Systems, Madison, WI 53719, USA; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Settles
authors.affiliation: Pan Genome Systems, Madison, WI 53719, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Kink
authors.affiliation: Pan Genome Systems, Madison, WI 53719, USA; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Food Hygiene and Control, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt. Electronic address: talaat@pangenosys.com.
authors.forename: Adel
authors.initials: A
authors.lastname: Talaat
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D004251:DNA Transposable Elements; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016927:Mycobacterium avium subsp. paratuberculosis / Q000145:classification* / Q000235:genetics; D010283:Paratuberculosis / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004251:DNA Transposable Elements; D007074:Immunoglobulin G; D020381:Interleukin-17; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D007371:Interferon-gamma
keywords: Johne's disease; Live attenuated vaccines; Paratuberculosis