Location: Infectious Bacterial Diseases ResearchTitle: Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice ) Author
Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/11/2014
Publication Date: 7/1/2014
Publication URL: http://handle.nal.usda.gov/10113/59512
Citation: Bannantine, J.P., Everman, J., Rose, S.J., Babrak, L., Katani, R., Barletta, R.G., Talaat, A.M., Grohn, Y.T., Chang, Y., Kapur, V., 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(88):1-8. Interpretive Summary: Johne’s disease in livestock such as dairy cattle, sheep and goats is caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). A commercial vaccine is available against MAP, but it is based on a killed whole-cell preparation of the bacterium. Furthermore, it is not used much in the U.S. because it interferes with TB skin testing of dairy cows and its efficacy could be improved. In this manuscript, we report the results of a mouse vaccine trial using 8 MAP vaccine strains, each containing a different mutation caused by a transposon. A systemic infection was confirmed by examining numbers of bacteria present in two mouse organs, the liver and spleen. Overall, the vaccines seemed to lower the bacterial numbers in the liver, compared to the spleen, but no vaccine significantly protected the mice from infection with the bacteria. Several assays were performed to demonstrate a good infection was obtained in the mice. This research is of primary interest to veterinarians, animal producers and researchers in the Johne’s disease and bovine-TB field.
Technical 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 vaccine strains demonstrated different levels of protection based on MAP colonization 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::Tn5367) was the most protective whereas strain 318 (intergenic Tn5367 insertion between MAP0282c and MAP0283c) had the most colonization. Selected vaccine strains that showed promise in the mouse model were moved forward into a goat challenge model.