Study of vaccines and new strategies for the control of goat tuberculosis

Resumen

Tuberculosis (TB) is an infectious disease caused by different members of the Mycobacterium tuberculosis complex (MTBC) which can affect a wide range of hosts, including different species of domestic and wild animals and humans. TB is still an important animal health issue with a high economic impact worldwide. In domestic animals, such as goats, TB control programs based on test-and-slaughter of positives are not always feasible. Therefore, the interest in the research on TB vaccination and vaccine-associated diagnostic tests for the disease control in animals has been renewed. In this regard, the present thesis provided insights into the efficacy of different vaccination strategies against caprine TB and vaccine-associated diagnostic tests in goats. The first study evaluated the efficacy in the field of a long-term vaccination of goats with the live-attenuated Bacilli Calmette-Guérin (BCG) vaccine (Danish 1331 strain) in five goat farms with different characteristics and management. The systematic vaccination of replacement goat kids with BCG contributed to a progressive reduction of TB incidence and prevalence in goat herds. The second study addressed the duration of immune responses elicited by BCG in goats and the efficacy of BCG vaccination and revaccination after one year. The lifespan of immune responses evoked by BCG vaccination was lower than one year and did not confer significant protection after M. caprae experimental challenge. On the contrary, BCG revaccination after one year of first vaccination provided better protection against M. caprae challenge. The third study evaluated the efficacy of the Heat-Inactivated Mycobacterium bovis (HIMB) vaccine candidate in experimentally M. caprae infected goats. Parenteral vaccination with HIMB showed similar protection to parenteral BCG vaccination, paving the way for its evaluation under field conditions. The fourth study assessed the performance of the antigen complex P22 (obtained by immunopurification of M. bovis tuberculin) for cell-mediated and serological immunodiagnosis of TB in goats under different vaccination contexts: BCG and Mycobacterium avium subesp. paratuberculosis (MAP) vaccination and MAP vaccination alone. In BCG and MAP vaccinated animals, combined interpretation of serological diagnostic using P22 and skin tests was a performant TB diagnostic strategy in terms of specificity and sensitivity. In all studies of the present thesis, the antigen cocktail based on ESAT-6 and CFP-10 proteins, applied for the Interferon-gamma release assay, was used for Differentiating infected from vaccinated animals (DIVA). Any diagnostic interference reaction was detected neither in BCG nor in BCG revaccinated, nor in HIMB vaccinated goats, confirming the suitability of ESAT-6 and CFP-10 antigen cocktail as a DIVA diagnostic test. Overall findings of the present thesis encourage the use of vaccines against TB and the vaccine-associated diagnostic tests as a useful strategy for control of TB in goats.