A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

A new (FET11) recombinant vaccine against paratuberculosis was developed based on recombinant antigens from acute and latent stages of Mycobacterium avium subsp. paratuberculosis (Map) infection.

In two experiments 28 calves and 15 goats were orally inoculated with live Map in their third week of life and post-exposure vaccinated at different times after inoculation or with different vaccine constructs. In contrast to common whole-cells vaccination, the FET11 vaccine did not interfere with tests for paratuberculosis or bovine tuberculosis as no measurable antibody responses by ID Screen® ELISA, PPDj-specific IFN-γ responses or positive PPDa or PPDb skin tests developed in vaccinees. Antibodies and cell-mediated immune responses were developed against FET11 antigens, however. At necropsy 8 or 12 months of age, relative Map burden was determined in a number of gut tissues by quantitative IS900 PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen® ELISA at 32 to 40 weeks p.i. indicating the progression of infection, while only four of 14 FET11 vaccinated calves seroconverted at 40-52 weeks p.i. Similarly, PPDj-induced IFN‐γ responses increased over time in non-vaccinated calves, while FET11 vaccinated calves had significantly reduced PPDj IFN-γ assay responses from 40 to 52 weeks compared to non-vaccinated calves. These results indicate the FET11 vaccine can be used to accelerate eradication of paratuberculosis while surveillance or test-and-manage control programs for tuberculosis and Johne’s disease remain in place.
Funded by EMIDA ERA-NET (219235), PoC East Denmark and Danish Research Council (FTP 274-08-0166)