Vaccination against paratuberculosis of lambs already infected experimentally with Mycobacterium avium subspecies paratuberculosis

Objective To assess the protective value of a live-attenuated vaccine in sh eep already exposed to Mycobacterium avium subsp paratuberculosis and to in vestigate the progression of a systemic immune response in experimentally i nfected sheep. Study design Twenty-eight lambs, aged 1 to 1.5 months, were dosed via stoma ch 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 m t of a live-attenuated vaccine. Thirteen additional lambs were neither dose d nor vaccinated (negative controls). Antigen-induced production of IFN-gam ma in blood, and antibody concentrations in serum were sequentially monitor ed in vaccinated, unvaccinated and control animals for 1 year. Each sheep w as examined for infection by an IS900-based PCR test on samples of ileum an d ileocaecal lymph node and histological examination at the time of necrops y. Results Seven of 14 unvaccinated and two of 14 vaccinated sheep developed c linical paratuberculosis that was later confirmed by histological examinati on and/or the IS900-based PCR test. The granulomatous inflammation in the j ejunal and ileal mucosa was less severe in vaccinated than in unvaccinated sheep. Acid-fast organisms were detected only in the unvaccinated group. Th e 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 unva ccinated sheep. Furthermore, in experimentally infected but unvaccinated sh eep, 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 ag ainst the organism and led to a reduced mycobacterial burden. The diminishe d IFN-gamma responses in experimentally infected sheep with acid-fast organ isms suggest a positive relationship between the magnitude of the systemic cell-mediated immune response and an animal's ability to control infection.