Efficacy of parenteral vaccination against tuberculosis with heat-inactivated <i>Mycobacterium bovis</i> in experimentally challenged goats

<div><p>Tuberculosis (TB) in animals is a re-emerging disease with a wide range of hosts that causes large economic losses in livestock. Goats are particularly susceptible to TB and, in endemic areas, vaccination may be a valuable measure to control the disease. The main aim of this study was to evaluate the efficacy of parenteral vaccination of goats with a heat-inactivated <i>Mycobacterium bovis</i> (HIMB) vaccine, and compare it to M. <i>bovis</i> Bacille Calmette–Guérin (BCG) vaccine. Twenty-four goat kids were divided in 3 groups as following: HIMB vaccinated group (n = 8), BCG vaccinated group (n = 8) and unvaccinated group (n = 8). Afterwards, goats were experimentally challenged with <i>Mycobacterium caprae</i> by the endobronchial route. Antigen specific interferon-γ release assays and serology were performed after vaccination and challenge. Pathological and bacteriological parameters were evaluated after necropsy at 9 weeks post-challenge (p.c.). HIMB vaccine showed similar levels of protection to BCG in terms of volume reduction of thoracic TB lesions, presence of extra-pulmonary lesions, as well as a slight reduction of bacterial load in pulmonary lymph nodes. Moreover, HIMB vaccine did not induce interferences on the interferon-γ release assay based on reagents previously developed to differentiate infected from BCG vaccinated individuals. The results indicate that HIMB is a suitable vaccine candidate for further larger-scale trials under field conditions in goats.</p></div

Correlation of Antigen-specific IFN-γ responses at week 17 and post mortem parameters.

<p>Correlation of Antigen-specific IFN-γ responses at week 17 and post mortem parameters.</p

Number of positive goats to each IFN-γ release assay.

<p>Number of positive goats to each IFN-γ release assay.</p

Number of animals with clinical signs after <i>M</i>. <i>caprae</i> challenge.

<p>Number of animals with clinical signs after <i>M</i>. <i>caprae</i> challenge.</p

Extrapulmonary lesions (generalization) in non-respiratory lymph nodes (LNs).

<p>Extrapulmonary lesions (generalization) in non-respiratory lymph nodes (LNs).</p

Whole blood antigen specific IFN-γ responses after vaccination and <i>M</i>. <i>caprae</i> challenge.

<p>The graphic shows the determination of the IFN-γ release by ELISA (expressed as ΔOD₄₅₀ ± CI) in plasma supernatants after blood stimulation with (A) <i>M</i>. <i>bovis</i> PPD (PPD-B), (B) ESAT-6/CFP-10 recombinant antigens mixture, (C) PC-HP cocktail and (D) PC-EC cocktail in unvaccinated control (n = 6), BCG vaccinated (n = 6) and HIMB vaccinated (n = 6) lambs.</p

Pulmonary lesion assessment results for the three experimental groups analyzed by computed tomography (CT).

<p>The volume of lung gross lesions, the ratio of the volume of lesions/volume of lungs, and the volume of calcification measured using computer tomography. Number of animals showing cavitary lesions is also shown.</p

Quantitative pathological results.

<p>(<b>A-C</b>) Individual volumes of TB lesions expressed in cm³. (<b>D-F</b>) Individual ratios between volumes expressed in %. (<b>A</b>) Total volume of lesions in pulmonary lymph nodes (LN). Groups: Control (n = 8), BCG (n = 8) and HIMB (n = 7). (<b>B</b>) Total volume of lung lesions. (<b>C</b>) Total volume of mineralized lesions in lungs. (<b>D</b>) Ratio of total volume of lung lesions / volume of the whole lung. (<b>E</b>) Ratio of total volume of lung mineralization / total volume of lung lesions. (<b>F</b>) Ratio of total volume of lung mineralization / volume of the whole lung. Groups (<b>B-F</b>): Control (n = 6), BCG (n = 7) and HIMB (n = 7). Horizontal lines represent median values. · <i>P</i> < 0.1, * <i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001, Kruskal-Wallis test with the <i>post hoc</i> Wilcoxon rank sum test with Bonferroni correction.</p

Distribution of extra-pulmonary lesions among groups.

<p>Distribution of extra-pulmonary lesions among groups.</p

Individual volume of pulmonary gross lesions measured by computed tomography (CT).

<p>The figure shows rendering images of the total lesion volume (expressed in cm³) for each lung of the 6 unvaccinated control, 6 BCG vaccinated and 6 HIMB vaccinated lambs. The trachea and the bronchial tree are also displayed for anatomical reference.</p