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

Abstract

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.