Combined vaccination of subcutaneous BCG and intranasal HBHA with cholera toxin enhances early protective immunity against pulmonary M. tuberculosis infection (VAC7P.972)

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Abstract Effect of Mycobacterium bovis bacille de Calmette et Guérin (BCG) vaccine on preventing adult pulmonary tuberculosis has been reported to be limited. Therefore, development of a novel effective vaccination strategy against pulmonary tuberculosis has become an international research priority. We have previously reported that intranasal administration of a recombinant mycobacterial Ag, heparin-binding heamagglutinin adhesin (HBHA), combined with mucosal adjuvant cholera toxin (CT) into mice enhanced Th1-type immune response and suppressed extrapulmonary bacterial dissemination after M. tuberculosis (Mtb) infection in the lung. Here, we further report effects of the mucosal HBHA+CT vaccine on murine experimental pulmonary Mtb infection. Combination of subcutaneous BCG priming vaccine followed by the mucosal HBHA+CT vaccine as a booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14. The combination of subcutaneous BCG and the mucosal HBHA+CT vaccine was more effective than the BCG vaccine alone in induction of the early protective immunity. Further, the mucosal HBHA+CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. The results indicate that the combination of BCG priming vaccine and mucosal HBHA+CT boosting vaccine might be a good candidate for a new vaccine strategy against pulmonary tuberculosis.