Abstract
Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn's disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne's Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne's disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis), or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 × 109 CFU divided in two consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate). All kids were necropsied at 13 months post-challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318) do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329) reduced fecal shedding and tissue colonization.
Highlights
There are conflicting data on the ability of current vaccines for Johne’s disease (JD) to reduce shedding of Mycobacterium avium subspecies paratuberculosis (MAP), and killed “whole cell” MAP vaccines often generate serious local tissue reaction and crossreactions to intradermal tests for M. bovis
The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne’s Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne’s disease goat challenge model
Our results suggest that vaccination with Silirum® does not prevent infection or eliminate MAP fecal shedding, it reduces presence of JD gross and microscopic lesions, slows progression of disease, reduces fecal shedding and reduces tissue colonization
Summary
There are conflicting data on the ability of current vaccines for Johne’s disease (JD) to reduce shedding of Mycobacterium avium subspecies paratuberculosis (MAP), and killed “whole cell” MAP vaccines often generate serious local tissue reaction and crossreactions to intradermal tests for M. bovis. This limits their usefulness for control programs (Rideout et al, 2003). No vaccine has been developed that elicits an immune response that completely eliminates viable MAP from the host (sterile immunity). In addition to its use in a control program, an efficacious vaccine could significantly reduce production losses and Frontiers in Cellular and Infection Microbiology www.frontiersin.org
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