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

Abstract

Abstract 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.