Mucosal delivery of antigen‐coated nanoparticles to lungs confers protective immunity against tuberculosis infection in mice

Mucosal boosting of BCG-immunised individuals with a subunit tuberculosis (TB) vaccine would be highly desirable, considering that the lungs are the principal port of entry for Mycobacterium tuberculosis (MTB) and the site of the primary infection and reactivation. However, the main roadblock for subunit TB vaccine development is the lack of suitable adjuvants that could induce robust local and systemic immune responses. Here, we describe a novel vaccine delivery system that was designed to mimic, in part, the MTB pathogen itself. The surface of yellow carnauba wax nanoparticles was coated with the highly immunogenic Ag85B Ag of MTB and they were directed to the alveolar epithelial surfaces by the incorporation of the heparin-binding hemagglutinin adhesion (HBHA) protein. Our results showed that the i.n. immunisation of BCG-primed BALB/c mice with nanoparticles adsorbed with Ag85B-HBHA (Nano-AH vaccine) induced robust humoral and cellular immune responses and IFN-γ production, and multifunctional CD4⁺ T cells expressing IFN-γ, IL-2 and TNF-α. Mice challenged with H37Rv MTB had a significantly reduced bacterial load in their lungs when compared with controls immunised with BCG alone. We therefore conclude that this immunisation approach is an effective means of boosting the BCG-induced anti-TB immunity.