Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice. tuberculosis (TB), a risk that can be up to 30 times higher in the setting of immunodeficiency such as that caused by HIV infection (World Health Organization, 2012). Consequently, an estimated 8.8 million new TB cases are currently reported annually, Rabbit Polyclonal to AIG1 with ~1.1 million TB-associated deaths among HIV-uninfected and K-7174 2HCl ~0.35 million among HIV coinfected people (World Health Organization, 2012). The available vaccine in the form of an attenuated Bacillus Calmette-Gurin (BCG) strain is clearly inadequate, and a more effective vaccine against active TB is urgently needed. An ideal antituberculous vaccine would protect against both infection with M.tb in exposed persons and the development of disease in those who have already been infected. The current BCG vaccine has limited protective capacity. Its main effect is partial protection against disseminated TB during early childhood with little or no impact on the development of reactivation TB later in life (reviewed in Colditz et al., 1994). Furthermore, this vaccine appears to have variable effectiveness due to considerable batch-to-batch variations as well as differences in BCG strains utilized for vaccination (Keyser et al., 2011). In addition, the BCG vaccine does not prevent infection with M.tb. Nevertheless, this vaccine has been in use for almost a century and remains the only approved vaccine against TB. Historically the most effective antimicrobial vaccines protect the host by generating antibody responses that neutralize the initial inoculum to prevent the establishment of infections (Robbins et al., 1995). In fact, all approved vaccines against bacterial pathogens, except for M.tb, are believed to mediate protection by generating an antibody response that neutralizes the infecting inoculum (Robbins et al., 1995). Unfortunately, it has been difficult to apply this successful formula for protection against TB because infection fails to consistently elicit protective Abs to M.tb (Glatman-Freedman, 2006). A clinically highly relevant alternate would be a vaccine that K-7174 2HCl would not protect against illness but would prevent disease. The association of TB with granuloma progression to caseous necrosis suggests that a vaccine that could promote and K-7174 2HCl enhance local containment might prevent both disease and transmission. In this regard, the fact that humoral immunity is definitely a potent mediator of swelling, and that some antibodies downregulate swelling (Buccheri et al., 2007), suggests that vaccines eliciting inflammation-modulating antibodies could protect by avoiding granulomas from progressing to caseous necrosis. Such a vaccine is definitely theoretically possible even though there is no precedent for this among licensed products. In this strategy the protective effect would be mediated by better control of mycobacteria in the granuloma through the addition of antibody effector mechanisms and/or better-organized granulomas. Several fresh TB vaccines and vaccination methods are in development, and many of those are K-7174 2HCl presently at numerous phases in medical tests. These have been extensively reviewed elsewhere (Checkley and McShane, 2011; Kaufmann, 2011) and will not be discussed in detail here. Most of the fresh vaccination strategies focus on either improving the current BCG vaccine or improving it with a second dose of BCG or a different TB vaccine. However, all of these strategies have in common the goal of focusing on the enhancement of cell-mediated immunity against M.tb. While there is no doubt that cell-mediated immunity is definitely a major component in the control of mycobacterial illness, there are now compelling data showing that protective Abdominal muscles against mycobacteria exist as discussed here and previously explained (Abebe and Bjune, 2009; Glatman-Freedman, 2006;Glatman-Freedman and Casadevall, 1998). Such data suggest that enhanced TB vaccine performance could be achieved by including methods that, in addition to cell-mediated immunity, also induce humoral immunity. In this regard, vaccines that elicit reactions from both arms of the adaptive immunity may work synergistically, given the interconnectedness between humoral and cellular immunity. However, antibody-based vaccine methods are still not becoming regarded as in the design of vaccines against TB. This is due to several.