The Use of Particulate Systems for Tuberculosis Prophylaxis and Treatment: Opportunities and Challenges.

The use of particles to develop vaccines and treatments for a wide variety of diseases has increased, and their success has been demonstrated in preclinical investigations. Accurately targeting cells and minimizing doses and adverse side effects, while inducing an adequate biological response, are important advantages that particulate systems offer. The most used particulate systems are liposomes and their derivatives, immunostimulatory complexes, virus-like particles, and organic or inorganic nano- and microparticles. Most of these systems have been proven using therapeutic or prophylactic approaches to control tuberculosis, one of the most important infectious diseases worldwide. This article reviews the progress and current state of the use of particles for the administration of TB vaccines and treatments in vitro and in vivo, with a special emphasis on polymeric particles. In addition, we discuss the challenges and benefits of using these particulate systems to provide researchers with an overview of the most promising strategies in current preclinical trials, offering a perspective on their progress to clinical trials.

Effect of mycobacterial proteins that target mitochondria on the alveolar macrophages activation during Mycobacterium tuberculosis infection.

Purpose of the study: During the early and progressive (late) stages of murine experimental pulmonary tuberculosis, the differential activation of macrophages contributes to disease development by controlling bacterial growth and immune regulation. Mycobacterial proteins P27 and PE_PGRS33 can target the mitochondria of macrophages. This study aims to evaluate the effect of both proteins on macrophage activation during mycobacterial infection. Materials and methods: We assess both proteins for mitochondrial oxygen consumption, and morphological changes, as well as bactericide activity, production of metabolites, cytokines, and activation markers in infected MQs. The cell line MH-S was used for all the experiments. Results: We show that P27 and PE_PGRS33 proteins modified mitochondrial dynamics, oxygen consumption, bacilli growth, cytokine production, and some genes that contribute to macrophage alternative activation and mycobacterial intracellular survival. Conclusions: Our findings showed that these bacterial proteins partially contribute to promoting M2 differentiation by altering mitochondrial metabolic activity.

Raw starch microparticles as BCG adjuvant: Their efficacy depends on the virulence of the infection strains.

The persistence of tuberculosis (TB) as one of the top 10 causes of death worldwide, the growing incidence of multidrug-resistant tuberculosis and the controversial efficacy of the Bacille Calmette-Guérin (BCG) vaccine drives the development of new generation multistage vaccines against this disease that can boost BCG-primed immunity. The use of polymeric microparticles for this purpose increases due to their advantages, especially their good safety levels and intrinsic immunostimulant properties. We recently explored and demonstrated the reinforcing and adjuvant potential of starch microparticles (SMPs) that administered intranasally to BCG-primed BALB/c mice, alone or in combination with a recombinant antigen, increased survival rates and induced a reduction of bacterial load in the lungs of mice infected with tuberculosis. Here, we tested the effect of SMPs added to the BCG vaccine as adjuvant to the whole-cell vaccine and investigated their contribution to the improvement of the protective efficacy of subcutaneous vaccination in mice challenged with virulent strains of Mycobacterium tuberculosis. As expected, our results were dependent on the infection strains, showing that virulence is a crucial factor that affects the adjuvant activity of SMPs. Our results also confirm the adjuvant activity of this carbohydrate and its usefulness in diverse vaccination strategies not only for mucosal but also for parenteral administration.