Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease

Authors: HINES II, MURRAY - University Of Georgia; TURNQUIST, SUE - University Of Georgia; ILHA, MARCIA - University Of Georgia; RAJEEV, SREEKUMARI - University Of Georgia; JONES, ARTHUR - University Of Georgia; WHITTINGTON, LISA - University Of Georgia; Bannantine, John; BARLETTA, RAUL - University Of Nebraska; GROHN, YRJO - Cornell University; KATANI, ROBAB - Pennsylvania State University; TALAAT, ADEL - University Of Wisconsin; LI, LINGLING - Pennsylvania State University; KAPUR, VIVEK - Pennsylvania State University

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2014
Publication Date: 3/4/2014
Publication URL: http://handle.nal.usda.gov/10113/58551
Citation: Hines II, M.E., Turnquist, S.E., Ilha, M.R., Rajeev, S., Jones, A.L., Whittington, L., Bannantine, J.P., Grohn, Y.T., Katani, R., Kapur, V. 2014. Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease. Frontiers in Microbiology. 4(26):1-14.

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. In this manuscript, we report the ability of 5 live MAP vaccine strains to protect against MAP infection using the goat model. Although several parameters were measured to identify which strain is the best vaccine to use, it was discovered that none of the live strains showed protection greater than that already provided by the killed whole-cell vaccine. This research is of primary interest to veterinarians, animal producers and researchers in the Johne’s disease and bovine-TB field.

Technical Abstract: A Mycobacterium avium subspecies paratuberculosis (MAP) vaccine that reduced the incidence of clinical disease and/or reduced fecal shedding of MAP would aid control of Johne’s disease (JD). The objectives of this study were 1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates alongside one commercially available MAP vaccine (Silirum®, Pfizer) using the protocols and endpoints 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 (see Hines et al., 2007b). Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with one of the experimental vaccines or once subcutaneously at 8 weeks with Silirum®, or an oral sham control vaccine consisting of goat milk. Kids were challenged orally with a total of approximately 1.44 X 10**9 CFU divided in 2 consecutive daily doses using a bovine MAP K10-like isolate (ATCC-700535). Immunological tests performed included Agar Gel Immunodiffusion (AGID), ELISA, and cell mediated response by comparative purified protein derivative (PPD) skin testing (M. avium, Johnin and M. bovis PPD’s). Kids within each group were euthanized and necropsied at 13 months post challenge. Results indicated all challenged kids had gross and/or microscopic lesions compatible with JD suggesting none of the vaccines prevented infection. However, there was a marked reduction in fecal CFU/g and necropsy lesion score in the group given the Silirum® vaccine and a lesser reduction in the 329 vaccine group. A marked reduction in MAP CFU/g and PCR percent positivity was also detected in necropsy tissues from kids given the Silirum® vaccine, and increased CFU/g were detected in tissues from kids given the 315 and 319 vaccines vs. the positive control group. Vaccination also resulted in false-positive PPD skin test reactions for M. avium PPD and Johnin. These data show Silirum® was the best performing vaccine followed by attenuated vaccine strain 329. Furthermore, the goat challenge model for Johne’s disease has been validated.