Inducible bronchus-associated lymphoid tissue plays an important role in the induction of antigen-specific immune response by Ag85B-hPIV2-based anti-tuberculosis vaccine in mice

Mycobacterium bovis bacilli Calmette-Guerin is the only licensed tuberculosis vaccine, which has been considered to be insufficient against adult pulmonary tuberculosis. As most of pathogens, including Mycobacterium tuberculosis , naturally enter the host through respiratory surface, nasal vaccine is an ideal method to prevent the diseases by inducing antigen-specific immune responses at respiratory sites as well as systemic compartments. Our group recently developed Ag85B-expressing human parainfluenza type 2 virus (Ag85B-hPIV2) as a nasal vaccine against tuberculosis. In this study, we aimed to elucidate the mechanisms underlying the induction of antigen-specific immune responses by Ag85B-hPIV2. We found that inducible bronchus-associated lymphoid tissue (iBALT) played an important role in the induction of antigen-specific immune responses. Intranasal administration of hPIV2 vector induced iBALT formation with induction of Th17 cells and CD11b + CD11c + cells both of which are known to require for the formation and maintenance of iBALT structure, respectively. When iBALT structure was disrupted by depletion of CD11b + cells in CD11b-diphtheria toxin receptor transgenic mice, Ag85B-specific immune response was diminished in the lung. These findings indicate that iBALT genesis is an essential process required in Ag85B-hPIV2 anti-tuberculosis mucosal vaccine.