Microstructured liposome subunit vaccines reduce lung inflammation and bacterial load after Mycobacterium tuberculosis infection

Abstract

BackgroundTuberculosis is a disease affecting millions of people throughout the world. One of the main problems in controlling the disease is the low efficacy of the Bacillus Calmette–Guérin (BCG) vaccine in protecting young adults. The development of new vaccines that induce a long-lasting immune response or that stimulate the immunity induced by BCG may improve the control of tuberculosis. MethodsThe use of microstructured liposomes containing HspX, with or without MPL or CpG DNA adjuvants, as vaccines for tuberculosis was evaluated. The HspX-specific humoral and cellular immune responses to the different vaccine formulations were compared. ResultsAll vaccines containing liposome microparticles and HspX were immunogenic. Vaccines formulated with CpG DNA and HspX induced the strongest humoral and cellular immune responses, mainly by inducing interferon-γ and tumor necrosis factor-α expression by both CD4+ and CD8+ T cells. HspX and MPL mainly induced CD8+ T-cell activation and specific humoral responses. When evaluated the protective efficacy of the formulations against Mycobacterium tuberculosis challenge, the microstructured liposome containing L-HspX and L-HspX-CPG DNA reduced both lung inflammatory lesions and the bacterial load. ConclusionWe have thus demonstrated, for the first time, the use of microstructured liposomes as an adjuvant and delivery system for a vaccine formulation against tuberculosis.