Abstract:
Novel vaccination strategies are crucial to efficiently control
tuberculosis, as proposed by the World Health Organization under its flagship program “End TB Strategy.” However, the emergence of drug-resistant strains of Mycobacterium tuberculosis
(Mtb), particularly in those coinfected 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 in addition displayed on the
surface a toll-like receptor-2ligand to offer to target dendritic cells
(DCs). Our results showed an efficient uptake of such a concoction
by DCs in a predominantly toll-like receptor-2–dependent
pathway. These DCs produced elevated levels of nitric oxide,
proinflammatory cytokines interleukin-6, interleukin-12, and
tumor necrosis factor-α, and upregulated the surface expression
of major histocompatibility complex class 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 tuberculosis infection.
