Multi-peptide subunit vaccination induced IFN-γ but lacked efficacy against Mycobacterium avium subsp. paratuberculosis in a goat challenge trial

Paratuberculosis is a chronic debilitating disease in ruminants caused by infection with Mycobacterium avium subsp. paratuberculosis (MAP). In endemic herds, animals are infected shortly after birth with no effective control measures beyond hygiene and sanitation programs. Current vaccines are only moderately effective and may interfere with surveillance and diagnosis of tuberculosis caused by M. bovis. In the current vaccination trial, we studied the efficacy of a vaccine against MAP in goats based on multiple 15-18 mer immunogenic peptides that are specific to MAP to not interfere with the diagnosis of bovine tuberculosis. All goats were experimentally inoculated with MAP bacteria at day 0, 3 and 7. The negative control group was left unvaccinated, and the positive control group was vaccinated with a single dose of a commercially available heat-inactivated whole-cell vaccine Gudair® in parallel with inoculation at day 0. Of the three vaccine groups, one group of goats was vaccinated with 23 peptides at day 0 (Pre23), other goats were post-exposure vaccinated 10 weeks after MAP inoculation with the same 23 peptides (Post23) or with 35 peptides (Post35). All peptide vaccinated groups were revaccinated with the same peptides 4 weeks later. The vaccines were immunogenic but were not able to induce a protective immune response and only the Gudair® vaccine was capable of lowering the MAP bacterial load in tissues. Adverse effects in the form of local reactions at the site of injection were seen after vaccination with Gudair® and with the peptide vaccines. The different combinations of peptides tested neither revealed an advantage of adding 12 extra peptides in the Post35 vaccine nor of post-exposure vaccination compared to vaccination at the time of infection.