Abstract
The “One world, one health” initiative emphasizes the need for new strategies to control human and animal tuberculosis (TB) based on their shared interface. A good example would be the development of novel universal vaccines against Mycobacterium tuberculosis complex (MTBC) infection. This study uses the goat model, a natural TB host, to assess the protective effectiveness of a new vaccine candidate in combination with Bacillus Calmette-Guerin (BCG) vaccine.Thirty-three goat kids were divided in three groups: Group 1) vaccinated with BCG (week 0), Group 2) vaccinated with BCG and boosted 8 weeks later with a recombinant adenovirus expressing the MTBC antigens Ag85A, TB10.4, TB9.8 and Acr2 (AdTBF), and Group 3) unvaccinated controls. Later on, an endobronchial challenge with a low dose of M. caprae was performed (week 15). After necropsy (week 28), the pulmonary gross pathology was quantified using high resolution Computed Tomography. Small granulomatous pulmonary lesions (< 0.5 cm diameter) were also evaluated through a comprehensive qualitative histopathological analysis. M. caprae CFU were counted from pulmonary lymph nodes.The AdTBF improved the effects of BCG reducing gross lesion volume and bacterial load, as well as increasing weight gain. The number of Ag85A-specific gamma interferon-producing memory T-cells was identified as a predictor of vaccine efficacy. Specific cellular and humoral responses were measured throughout the 13-week post-challenge period, and correlated with the severity of lesions.Unvaccinated goats exhibited the typical pathological features of active TB in humans and domestic ruminants, while vaccinated goats showed only very small lesions. The data presented in this study indicate that multi-antigenic adenoviral vectored vaccines boosts protection conferred by vaccination with BCG.
Highlights
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is one of the most important causes of infectious disease mortality and morbidity in humans worldwide [1]
Clinical signs and body weight Clinical signs typical of caprine TB were monitored from the M. caprae challenge to the end point of the study
The mean body weight increase during this period was significantly lower in unvaccinated control animals (249 g/week, 95% CI: 230-269) in comparison to Bacillus Calmette-Guerin (BCG)-AdTBF group (403 g/week, 95% CI: 383-423, P,0.001) and BCG group (351 g/week, 95% CI: 331-370, P,0.05)
Summary
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis, is one of the most important causes of infectious disease mortality and morbidity in humans worldwide [1]. M. bovis and M. caprae, members of the M. tuberculosis complex (MTBC), are the main causative agents of bovine and caprine TB, respectively. The latter is considered an emerging disease in a number of European countries, causing increasing economic losses to the livestock sector [3,4,5]. Goats infected with M. caprae may be a source of infection for cattle, acting as domestic reservoirs of bovine TB [6].
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