However, a number of studies have demonstrated that the efficacy of BCG against TB wanes over time and provides little or no protection against pulmonary TB in adolescents and adults [6]. Furthermore, according to the WHO recommendation, BCG vaccination should not be given to HIV-infected infants because of a high risk of disseminated infection [7, 8]. Therefore, a novel, safe, and effective vaccine against TB for both HIV-negative and HIV-positive individuals is urgently Selleck ZD1839 needed. For preexposure, two main approaches

are currently being evaluated [6, 9]. The first approach involves generating modified mycobacteria that would be more effective than BCG with present examples including VPM 1002, rBCG30, and MIP [6]. The second Protein Tyrosine Kinase inhibitor approach relies on the development of a “prime-boost” vaccination strategy consisting of a primary BCG vaccination in newborns and a follow-up booster subunit vaccine, such as recombinant mycobacterial proteins formulated in adjuvants (M72, Hybrid-1, Hyvac 4, H56, and ID93), and recombinant viral vectors expressing mycobacterial proteins (MVA85A, Aeras-402, and AdAg85A). In the case of postexposure, subunits vaccines would be built as immunotherapeutic agents in combination with antibiotics. Exosomes are 50–150 nm membrane vesicles originating from multivesicular bodies by inward

budding of endosomal membranes and are released by hematopoietic and nonhematopoietic cells via the fusion of the limiting membrane of multivesicular bodies to the plasma membrane [10, 11]. These membrane vesicles

were originally defined as a mechanism to eliminate surface membrane receptors such as the transferrin receptor from maturing reticulocytes [12, 13]. Subsequently, it was determined that EBV-transfomed B lymphocytes release exosomes containing major histocompatibility complex (MHC) class II molecules with bound peptides, which were able to activate antigen-specific T cells in vivo. This suggests a role for exosomes in promoting an acquired Protein tyrosine phosphatase immune response [14]. The feasibility of using antigen-containing exosomes as a novel cell-free tumor vaccine has been investigated in some detail [15-18]. Our previous studies determined that cultured macrophages infected with M. tuberculosis or pulsed with M. tuberculosis culture filtrate protein (CFP) released exosomes containing mycobacterial components including antigenic proteins and lipids, and were capable of priming a mycobacterial antigen-specific T-cell response in mice [19-21]. However, it remained unclear whether these exosomes were able to protect against an M. tuberculosis infection. In this study, we investigated the vaccine efficacy of exosomes against TB in both naïve and prior BCG-immunized mice. The M.