|BARNHILL, A - Former ARS Employee|
|CHANG, Y - Cornell University|
|OSMAN, M - Iowa State University|
Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2012
Publication Date: 11/6/2012
Citation: Stabel, J.R., Barnhill, A., Bannantine, J.P., Chang, Y.F., Osman, M.A. 2012. Evaluation of protection in a mouse model after vaccination with Mycobacterium avium subsp. paratuberculosis protein cocktails. Vaccine. 31(1):127-134.
Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle, sheep and wild ruminants, characterized by diarrhea, reduced feed intake, weight loss and death. Animals usually become infected when they are young by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced production by these animals through reduced milk production, they also present a potential infective threat to the rest of the herd. Vaccination is one method of managing the spread of this disease as it may reduce fecal shedding of the organism. However, some major disadvantages of the current vaccine are that animals become positive on serologic diagnostic tests for paratuberculosis. Vaccination against paratuberculosis may also cause false-positive reactions on tuberculin skin tests. Using specific proteins for the vaccine instead of the whole-cell bacterium allows for diagnostic tests to discern between vaccinated and infected animals. In the present study, vaccination with a cocktail of three proteins resulted in protection against infection. These results are important considerations for producers considering the use of vaccination as a management tool in infected herds.
Technical Abstract: Whole-cell vaccines successfully reduce signs of clinical disease and fecal shedding of Mycobacterium avium subsp. paratuberculosis (MAP), however, these vaccines have some limitations. The present study was conducted to identify MAP proteins that might be candidates for the development of an improved vaccine. MAP proteins were screened for immunogenicity in naturally infected cattle and selected based upon reactivity in the interferon-gamma (IFN-gamma) and Western blot assays. Proteins (MAP1087, MAP1204, MAP1272c, and MAP2077c) were arrayed into 4 overlapping cocktails containing 3 proteins each. The efficacy of the proteins within these cocktails as vaccine candidates was evaluated by subcutaneous immunization of mice, followed by challenge with live, virulent MAP. All MAP protein cocktails significantly reduced the recovery of live MAP from the ileum, while cocktails 1 and 3 reduced colonization in the liver. No significant differences were seen in the mesenteric lymph node or spleen, however, cocktail 1 reduced viable MAP in the mesenteric lymph node compared to other treatments. Stimulation of splenocytes upregulated antigen-specific IFN-gamma and IL-23 secretion in all treatment groups, regardless of vaccination. Interestingly, IL-4 was moderately downregulated for vaccinates compared to control infected mice. An increase in total CD25 expression was noted for 3 of the 4 vaccinate groups upon stimulation of splenocytes with MPS, with this effect becoming more significant within CD4CD25+ and CD8CD25+ subpopulations. The present study demonstrated that MAP proteins are useful as immunogens to reduce MAP tissue burden.