OR19

1:Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Catalonia, Spain.; 2:Animal Health Department, NEIKER-Instituto Vasco de Investigación y Desarrollo Agrario, Basque Research and Technology Alliance (BRTA), Derio, 48160, Bizkaia, Basque Country, Spain. Development (NEIKER); 3:Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona, Bellaterra, 08193, Catalonia, Spain.

Currently, Bacille Calmette-Guérin (BCG) is the only approved vaccine for tuberculosis (TB) in humans, and no licensed vaccine is available for livestock. Nevertheless, both BCG and heat-inactivated Mycobacterium bovis (HIMB), when administered parenterally, have shown variable levels of protection under experimental and field conditions. A vaccine that effectively prevents infection and reliable immune correlates of protection are urgently needed. This study evaluated the immunogenicity of mucosal TB vaccination approaches by analysing systemic and local, in the lung mucosa, immune responses of goats. Thirty animals were divided into five groups: 1) intranasal (i.n.) BCG, 2) i.n. HIMB, 3) i.n. HIMB with mucosal adjuvant (HIMBmuc), 4) subcutaneous (s.c.) HIMB prime followed by i.n. HIMBmuc boost, and 5) s.c. BCG prime followed by i.n. HIMBmuc boost. Antigen-specific cytokines and IFN-γ-producing T-cell subsets in blood and bronchoalveolar lavage fluid (BALF) were measured by ELISA and flow cytometry, respectively. Activation and proinflammatory markers in alveolar macrophage (AM) were also analysed. Intranasal BCG and both prime-boost groups induced higher systemic specific IFN-γ levels, increased CD4+ and CD8+ IFN-γ–producing T-cells and greater IFN-γ production in effector and memory CD4+ T-cells in peripheral blood compared to HIMB i.n. groups. Moreover, proinflammatory cytokines (TNF-α, IL-17A and IFN-γ) were elevated in BALF, and greater AM activation and polarization were observed in those groups. These results highlight the potential of intranasal BCG and prime-boost strategies to elicit robust mucosal and systemic immunity against TB, and of intranasal BCG or HIMB booster vaccines for improving protective immunity at the pulmonary mucosal surface.