Development of New Preventive and Therapeutic Vaccines for Tuberculosis

Abstract

Tuberculosis (TB) is a contagious disease that has been responsible for the death of one billion people in the last 200 years. Until now, the only vaccine approved for the prevention of TB is Bacillus Calmette-Guérin (BCG), which is prepared by attenuating Mycobacterium bovis. However, one of the limitations of BCG is that its preventive effect against pulmonary TB varies from person to person. Therefore, there arises a need for a new TB vaccine to replace or supplement BCG. In this review, we have summarized the findings of current clinical trials on preventive and therapeutic TB vaccine candidates. In addition, we have discussed a novel vaccination approach using the cell-based vaccine presenting early secretory antigenic target-6 (ESAT-6), which is a potent immunogenic antigen. The role of ESAT-6 in hosts has also been described.

RNA Sensing of Mycobacterium tuberculosis and Its Impact on TB Vaccination Strategies

“…Still, BCG is the widest used vaccine in the world. Advantages in the development of new TB vaccines have recently been extensively reviewed [111][112][113][114], therefore in this review, we focus on immunological mechanisms in vaccine-strategies with regard to pathways involving RNA sensing (Figure 3).…”

Novel Vaccine Candidates against Tuberculosis

“…Another recent subunit vaccine is ID93/GLA-SE composed of recombinant fusion protein ID93 and adjuvant GLA-SE from the Infectious Disease Research Institute. ID93 contains 4 M. tuberculosis antigens (Rv2608, Rv3619, Rv3620 and Rv1813) and GLA-SE is a TLR4L-containing adjuvant that helps to induce Th1 immune responses [79]. ID93/GLA-SE can induce multifunctional IFN-γ, TNF-α, IL-2 and CD4 T cells in mice and guinea pigs with or without BCG vaccination.…”

Latest Comprehensive Knowledge of the Crosstalk between TLR Signaling and Mycobacteria and the Antigens Driving the Process

“…Dimerization of TLRs results from ligand binding, which triggers the recruitment of adaptor proteins to the intracellular TIR domain. Vertebrate TLRs are classified using sequence homology into six families, namely TLR1 (1, 2, 6, 10), TLR3, TLR4, TLR5, TLR7 (7,8,9), and TLR11 (11,12,13). Cell surface TLRs include TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10, whereas intracellular TLRs include TLR3, TLR7, TLR8, TLR9, TLR11, TLR12, and TLR13 in endosomes and lysosomes.…”

“…In addition, TB-related problems have been identified a recognized in the past, but their severity has been more recently emphasized because of emerging antibiotic resistance in Mtb and the risk of re-infection [7]. There is an urgent need to develop effective treatments for TB considering various aspects such as treatment duration, potential drug toxicity, and drug-drug interactions [8]. To devise a novel strategy against TB, it is necessary to understand the mechanisms by which Mtb is recognized by the host immune system.…”