Journal of Medical Microbiology
June 2014; 63 (Pt 6)
http://jmm.sgmjournals.org/content/current

Vaccine against tuberculosis: a view
Om Parkash
Author Affiliations
Scientist- E (Immunology), National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra-282004, India
Excerpt
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, continues to be a big health problem (WHO, 2013), particularly given the emergence of multidrug-resistant, extensively drug-resistant and totally drug-resistant strains of M. tuberculosis, which makes it more difficult to treat the infected individuals (Velayati et al., 2009; Falzon et al., 2011; Zignol et al., 2012). Moreover, the global epidemic of human immunodeficiency virus (HIV)/AIDS has added to the load of TB patients, further worsening the problem (Harries et al., 2010). According to a WHO report of 2013, TB afflicted about 8.6 million individuals and it caused death in more than 1.3 million cases in that year (WHO, 2013), indicating that it is a major scourge amongst infectious diseases. Chemotherapy of active TB saved the lives of many millions of patients, but extending it to chemoprophylaxis of latently infected subjects has not been implemented due to the excessive cost that would be involved. Hence, the availability of an effective vaccine could prove to be an affordable tool, with a major impact on the TB epidemic and thereby on the global elimination of the disease. Therefore, a search for the development of an effective vaccine has attracted a great deal of attention over the years. Thus far, Bacille Calmette–Guérin (BCG) remains the only licensed vaccine which has been used worldwide (Colditz et al., 1994; Zwerling et al., 2011). Its administration soon after birth can prevent severe forms of childhood TB. However, there is general agreement that BCG confers insufficient protection against TB in adolescents and adults. Currently, several candidate prophylactic vaccines have reached clinical trials (Kaufmann, 2013), but as yet, no new approved vaccine is available for immunoprophylactic use in the population. A major challenge for developing more efficacious vaccines against TB is the incomplete understanding of the mechanism of immunity and the mechanisms of immune evasion and subversion by M. tuberculosis….
…In conclusion, it is argued that despite inducing potent Th1 memory, anti-TB vaccines may not be protective against TB. This view is supported by the known inconsistent efficacy of BCG vaccination (Andersen & Doherty, 2005), the uncertainties regarding candidate vaccines (Kaufmann et al., 2010; Kaufmann, 2013) and the recent failure of a phase 2b TB vaccine trial in infants (Tameris et al., 2013). In all the foregoing approaches, generation of Th1-mediated protective immunity was the major aim to make the vaccines effective. What could be the remedy when Th1-mediated immunity fails? Probably, the answer may be sought by exploring alternative approaches, involving CD8+ T-cells, natural killer T-cells and γδ T-cells (Yoshikai, 2006; Barnes et al., 2009; Cooper, 2009) for generation of protective immunity by candidate vaccines. The reasons supporting this suggestion are that: (i) these cells are understood to contribute towards protection against M. tuberculosis; also, (ii) these cells do not require antigen presentation in association with MHC-II molecules. However, these still rely on antigen presentation in association with MHC-I or CD1, which could also be affected by M. tuberculosis (Baena & Porcelli, 2009). Regarding antibodies, there are several pieces of evidence indicating their contribution towards protection against TB (Achkar & Casadevall, 2013). However, their role in protecting against TB is controversial, as yet. Nevertheless, with vaccination, antibodies can be generated prior to infection, and for production of antibodies, processing and presentation of M. tuberculosis antigens are not required. Moreover, there is evidence that antibodies can affect downstream processing and presentation of antigens for generation of CMI. Therefore, the humoral response may help in preventing infection and is worth considering for developing an anti-TB vaccine. Thus, a combined approach, involving multiple antigens targeting multiple cells, deserves attention for further research for developing an anti-TB vaccine. Probably, such a formulation may lead to a better alternative anti-TB vaccine by providing a greater ability for the host to recognize a wider range of M. tuberculosis antigens.