title: Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice.
abstract: Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants showed no survival in those tissues, indicating their complete attenuation in the mouse model. The candidate vaccine strains demonstrated different levels of protection based on colonization of the challenge strain in liver and spleen tissues at 12 and 18 weeks post vaccination. Based on total MAP burden in both tissues at both time points, strain 315 (MAP1566::Tn5370) was the most protective whereas strain 318 (intergenic Tn5367 insertion between MAP0282c and MAP0283c) had the most colonization. Mice vaccinated with an undiluted commercial vaccine preparation displayed the highest bacterial burden as well as enlarged spleens indicative of a strong infection. Selected vaccine strains that showed promise in the mouse model were moved forward into a goat challenge model. The results suggest that the mouse trial, as conducted, may have a relatively poor predictive value for protection in a ruminant host such as goats.
authors: Infectious Bacterial Diseases, National Animal Disease Center, USDA-ARS Ames, IA, USA.
authors: John P
authors: JP
authors: Bannantine
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University Corvallis, OR, USA ; Department of Microbiology, College of Science, Oregon State University Corvallis, OR, USA.
authors: Jamie L
authors: JL
authors: Everman
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University Corvallis, OR, USA ; Department of Microbiology, College of Science, Oregon State University Corvallis, OR, USA.
authors: Sasha J
authors: SJ
authors: Rose
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University Corvallis, OR, USA ; Department of Microbiology, College of Science, Oregon State University Corvallis, OR, USA.
authors: Lmar
authors: L
authors: Babrak
authors: Department of Veterinary and Biomedical Sciences, Pennsylvania State University University Park, PA, USA.
authors: Robab
authors: R
authors: Katani
authors: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska Lincoln, NE, USA.
authors: Raúl G
authors: RG
authors: Barletta
authors: Department of Pathobiological Sciences, University of Wisconsin-Madison Madison, WI, USA ; Department of Food Hygiene, Cairo University Cairo, Egypt.
authors: Adel M
authors: AM
authors: Talaat
authors: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University Ithaca, NY, USA.
authors: Yrjö T
authors: YT
authors: Gröhn
authors: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University Ithaca, NY, USA.
authors: Yung-Fu
authors: YF
authors: Chang
authors: Department of Veterinary and Biomedical Sciences, Pennsylvania State University University Park, PA, USA.
authors: Vivek
authors: V
authors: Kapur
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University Corvallis, OR, USA ; Department of Microbiology, College of Science, Oregon State University Corvallis, OR, USA.
authors: Luiz E
authors: LE
authors: Bermudez
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002417:Cattle; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009154:Mutation; D016927:Mycobacterium avium subsp. paratuberculosis / Q000235:genetics / Q000276:immunology*; D010283:Paratuberculosis / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated
keywords: Johne's disease; Mycobacterium; attenuated; genomics; mouse model; vaccines