IMMUNOLOGY AND INTERVENTION STRATEGIES FOR JOHNE'S DISEASE
Location: Infectious Bacterial Diseases Research Unit
Title: Activation of host immune responses in neonatal calves and interference with TB diagnostics after immunization with a commercial heat-killed vaccine
Submitted to: Meeting Proceedings
Publication Type: Proceedings
Publication Acceptance Date: February 4, 2012
Publication Date: February 19, 2012
Citation: Stabel, J.R., Waters, W.R., Bannantine, J.P., Lyashchenko, K. 2012. Activation of host immune responses in neonatal calves and interference with TB diagnostics after immunization with a commercial heat-killed vaccine. In: Proceedings of 11th International Colloquium on Paratuberculosis, February 5-10, 2012, Sydney, Australia. p. 126-129.
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 vaccination are that animals become positive on serologic diagnostic tests for paratuberculosis. Vaccination against paratuberculosis may also cause false-positive reactions on tuberculin skin tests. In this paper, we present results from a study designed to evaluate effects of vaccination on current diagnostic tests for paratuberculosis and bovine tuberculosis. Further, we measured host immune responses to define protective immunity after vaccination. Results of this study suggest that vaccination does result in positive serologic tests for paratuberculosis, however, there was no interference with tests for bovine tuberculosis. These results are important considerations for producers considering the use of vaccination as a management tool in infected herds.
A major drawback of current whole-cell vaccines for Mycobacterium avium subsp. paratuberculosis is the potential interference with diagnostic tests for bovine tuberculosis and paratuberculosis. The current study was designed to explore cross-reactivity of the current USDA commercial vaccine for MAP with diagnostic tools for bovine TB and to assess host responses to vaccination. Neonatal dairy calves were assigned to treatment groups consisting of: 1) Control – no vaccine (n = 5); and 2) Vaccinate – Mycopar vaccine (n = 5). Blood and fecal samples were collected prior to the initiation of the study for pre-vaccination measurements. Calves were vaccinated subcutaneously with a 0.5 ml dose in the dewlap-brisket area as per standard procedure with the wild-type commercial vaccine that consists of a heat-killed whole cell suspension of MAP in oil (Mycopar). Calves were sampled throughout the study on days 7, 14, 28, and at 3, 6, 9, and 12 months. Comparative cervical skin testing was performed at 6 months both as a diagnostic tool and to determine in vivo cell-mediated response to vaccination. For determination of M. bovis-specific antibody, the TB Stat-Pak assay and the dual-path platform (DPP) VetT B assay (Chembio Diagnostic Systems) were performed. Peripheral blood mononuclear cells were isolated before and after vaccination and stimulated in vitro for measurement of interferon-(IFN)-gamma, interleukin (IL)-4, IL-10, and IL-12, and to assess differences in lymphocyte populations by flow cytometry. Results from this study demonstrated a rapid initiation of MAP-specific IFN-gamma in Vaccinate calves by 7 days, with robust responses continuing throughout the study. Vaccinate calves also had IFN-gamma responses to BoPPD, with moderate reactivity to ESAT-6/CFP-10, an M. bovis recombinant fusion protein. Interestingly, IL-4 and IL-10 were markedly decreased in Vaccinate calves only on days 7 and 14 of the study and thereafter were similar to Controls. Vaccinate calves began to seroconvert at 4 months with all calves having detectable MAP antibody by 6 months. Only one Vaccinate calf had a positive (suspect) skin test response to M. bovis PPD and none of these calves reacted in M. bovis serologic tests. These results suggest that vaccination with Mycopar will interfere with diagnostic tools for the detection of paratuberculosis but have low interference with M. bovis diagnostics.