Superior Protection from Live-Attenuated Vaccines Directed against Johne's Disease.
Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the etiological agent of Johne's disease in ruminants. Johne's disease is an important enteric infection causing large economic losses associated with infected herds. In an attempt to fight this infection, we created two novel live-attenuated vaccine candidates with mutations in sigH and lipN (pgsH and pgsN, respectively). Earlier reports in mice suggested these vaccines are promising candidates to fight Johne's disease in ruminants. In this study, we tested the performances of the two constructs as vaccine candidates using the goat model of Johne's disease. Both vaccines appeared to provide significant immunity to goats against challenge from wild-type M. paratuberculosis The pgsH and pgsN constructs showed a significant reduction in histopathological lesions and tissue colonization compared to nonvaccinated goats and those vaccinated with an inactivated vaccine. Unlike the inactivated vaccine, the pgsN construct was able to eliminate fecal shedding from challenged animals, a feature that is highly desirable to control Johne's disease in infected herds. Furthermore, strong initial cell-mediated immune responses were elicited in goats vaccinated with pgsN that were not demonstrated in other vaccine groups. Overall, the results indicate the potential use of live-attenuated vaccines to control intracellular pathogens, including M. paratuberculosis, and warrant further testing in cattle, the main target for Johne's disease control programs.
Pan Genome Systems, Madison, Wisconsin, USA.
Daniel C
DC
Shippy
Pan Genome Systems, Madison, Wisconsin, USA.
Justin J
JJ
Lemke
Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Aubrey
A
Berry
Research Animal Resources Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Kathryn
K
Nelson
Tifton Veterinary Diagnostic and Investigational Laboratory, College of Veterinary Medicine, University of Georgia, Tifton, Georgia, USA.
Murray E
ME
Hines
Pan Genome Systems, Madison, Wisconsin, USA atalaat@wisc.edu.|Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Adel M
AM
Talaat
D056704:Adaptive Immunity; D000818:Animals; D058491:Bacterial Load; D057138:Bacterial Shedding; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005798:Genes, Bacterial; D015511:Goat Diseases / Q000517:prevention & control*; D006041:Goats; D006651:Histocytochemistry; D007111:Immunity, Cellular; D008297:Male; D009154:Mutation; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology* / Q000302:isolation & purification; D010283:Paratuberculosis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics
D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D037521:Virulence Factors
Johne's disease; adjuvant; live-attenuated vaccine; pathogenesis; protective immunity