Targeting dendritic cells with TLR-2 ligand-coated nanoparticles loaded with Mycobacterium tuberculosis epitope induce anti-tuberculosis immunity.

Novel vaccination strategies are crucial to efficiently control tuberculosis, as proposed by WHO under its flagship program 'End TB Strategy'. However, the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), particularly in those co-infected with HIV-AIDS, constitutes a major impediment to achieving this goal. We report here a novel vaccination strategy that involves synthesizing a formulation of an immunodominant peptide derived from the Acr1 protein of Mtb. This nanoformulation additionally displayed a toll-like receptor-2 (TLR-2) ligand to offer to target dendritic cells (DCs). Our results showed an efficient uptake of such a concoction by DCs in a predominantly TLR-2-dependent pathway. These dendritic cells produced elevated levels of nitric oxide, pro-inflammatory cytokines IL-6, IL-12, and TNF-α, and upregulated the surface expression of class MHC II molecules, as well as costimulatory molecules such as CD80 and CD86. Animals injected with such a vaccine mounted a significantly higher response of effector and memory Th1 cells and Th17 cells. Furthermore, we noticed a reduction in the bacterial load in the lungs of animals challenged with aerosolized live Mtb. Therefore, our findings indicated that the described vaccine triggered protective anti-Mtb immunity to control the TB infection.