title: Vaccination against paratuberculosis of lambs already infected experimentally with Mycobacterium avium subspecies paratuberculosis.
abstract: OBJECTIVE
  To assess the protective value of a live-attenuated vaccine in sheep already exposed to Mycobacterium avium subsp paratuberculosis and to investigate the progression of a systemic immune response in experimentally infected sheep.
  
  
  METHODS
  Twenty-eight lambs, aged 1 to 1.5 months, were dosed via stomach tube with approximately 4.4 x 10(8) M a paratuberculosis organisms. Two weeks later, 14 of these 28 animals received subcutaneous injections of 1 mL of a live-attenuated vaccine. Thirteen additional lambs were neither dosed nor vaccinated (negative controls). Antigen-induced production of IFN-gamma in blood, and antibody concentrations in serum were sequentially monitored in vaccinated, unvaccinated and control animals for 1 year. Each sheep was examined for infection by an IS900-based PCR test on samples of ileum and ileocaecal lymph node and histological examination at the time of necropsy.
  
  
  RESULTS
  Seven of 14 unvaccinated and two of 14 vaccinated sheep developed clinical paratuberculosis that was later confirmed by histological examination and/or the IS900-based PCR test. The granulomatous inflammation in the jejunal and ileal mucosa was less severe in vaccinated than in unvaccinated sheep. Acid-fast organisms were detected only in the unvaccinated group. The PCR assay on ileal samples gave positive reactions in two vaccinated and eight unvaccinated sheep. Both the antibody response and IFN-gamma response were detected earlier and were more substantial in vaccinated than in unvaccinated sheep. Furthermore, in experimentally infected but unvaccinated sheep, the IFN-gamma concentrations were higher in those animals without acid-fast organisms than in those with them.
  
  
  CONCLUSIONS
  Vaccination of lambs with live-attenuated vaccine 2 weeks after oral inoculation with M a paratuberculosis stimulated the host response against the organism and led to a reduced mycobacterial burden. The diminished IFN-gamma responses in experimentally infected sheep with acid-fast organisms suggest a positive relationship between the magnitude of the systemic cell-mediated immune response and an animal's ability to control infection.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand. Jacek.Gwozdz@nre.vic.gov.au
authors.forename: J M
authors.initials: JM
authors.lastname: Gwozdz
authors.forename: K G
authors.initials: KG
authors.lastname: Thompson
authors.forename: B W
authors.initials: BW
authors.lastname: Manktelow
authors.forename: A
authors.initials: A
authors.lastname: Murray
authors.forename: D M
authors.initials: DM
authors.lastname: West
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005243:Feces / Q000382:microbiology; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010283:Paratuberculosis / Q000276:immunology / Q000517:prevention & control*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000662:veterinary*; D014613:Vaccines, Attenuated
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma