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Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice

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  • 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 andMAP0283c) 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.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Frontiers Research Foundation. The published article can be found at: http://www.frontiersin.org/Cellular_and_Infection_Microbiology.
  • Keywords: Johne’s disease, Mouse model, Attenuated, Mycobacterium, Vaccines, Genomics
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  • Bannantine, J. P., Everman, J. L., Rose, S. J., Babrak, L., Katani, R., Barletta, R. G., ... & Bermudez, L. E. (2014). Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice. Frontiers in Cellular and Infection Microbiology, 4, 84. doi:10.3389/fcimb.2014.00088
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  • 4
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  • Funding for conducting the three-phase vaccine trial was provided by the USDA-CAP grant JDIP and by USDA-APHIS.This work was also partially supported by NIFA Animal Health Projects (NEB-39-162 to Raúl G. Barletta) and the animal formula fund (NY-478-437 to Yung-Fu Chang).
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