Tuberculosis Vaccine: Past Experiences and Future Prospects

Abstract

Vaccines are the best prophylactic measure that have eradicated several diseases like polio, measles, and small pox. Currently, efficient vaccines are unavailable for many dreaded diseases, including tuberculosis (TB). TB is caused by an intracellular pathogen Mycobacterium tuberculosis (Mtb) and is responsible for about two million deaths and nine million new cases annually. The WHO has announced TB as a global emergency in the wake of emerging multidrug-resistant, extremely drug-resistant, and totally drug-resistant strains of Mtb. An alarming increase in the number of TB cases around the world and its co-occurrence with HIV has further complicated the problem. Additionally, BCG has failed in reducing the global TB burden, despite its widespread usage. Interestingly, BCG protects children from TB, indicating that it has sufficient antigenic repertoire to protect against Mtb. In contrast, failure to protect adults, suggests BCG inability to generate long-lasting immunological memory. Further, protection rendered by BCG against pulmonary TB in adults is highly inconsistent, varying from 0% to 85% (Andersen and Doherty, Nat Rev Microbiol 3:656–62, 2005). Furthermore, its efficacy is least in TB-endemic countries. Studies conducted in Malawi, India, and other endemic countries have concluded that BCG induces inadequate protection. The probable reasons suggested are the interference by nontuberculous mycobacteria (NTM) in antigen processing and presentation of antigen-presenting cells (APCs), latent TB infection (LTBI), and high prevalence of helminth infestation. There are currently 12 vaccine candidates in clinical trials, including recombinant BCG vaccines, attenuated Mtb strains, recombinant viral-vectored platforms, protein/adjuvant combinations, and mycobacterial extracts (WHO, Global tuberculosis report, 2017). However, the whole-cell vaccine candidates may encounter same problem in TB-endemic population, as mentioned above for BCG. Therefore, radically novel strategies of vaccination against Mtb are urgently needed. Peptide vaccines can be a possible alternative to overcome the failures of BCG because it comprises of epitopes that can directly bind to MHC molecules, circumventing the interference of NTM and latent Mtb in antigen processing. Furthermore, epitopes from multiple stages like LTBI, active, chronic, and drug-resistant Mtb can be selected. In essence, peptide-based prophylactic and therapeutic vaccines represent a promising future strategy for efficient management of TB.