Vaccination Strategies Against Mycobacterium tuberculosis: BCG and Beyond

Tuberculosis (TB) is a highly contagious disease caused by Mycobacterium tuberculosis (Mtb) and is the major cause of morbidity and mortality across the globe. The clinical outcome of TB infection and susceptibility varies among individuals and even among different populations, contributed by host genetic factors such as polymorphism in the human leukocyte antigen (HLA) alleles as well as in cytokine genes, nutritional differences between populations, immunometabolism, and other environmental factors. Till now, BCG is the only vaccine available to prevent TB but the protection rendered by BCG against pulmonary TB is not uniform. To deliver a vaccine which can give consistent protection against TB is a great challenge with rising burden of drug-resistant TB. Thus, expectations are quite high with new generation vaccines that will improve the efficiency of BCG without showing any discordance for all forms of TB, effective for individual of all ages in all parts of the world. In order to enhance or improve the efficacy of BCG, different strategies are being implemented by considering the immunogenicity of various Mtb virulence factors as well as of the recombinant strains, co-administration with adjuvants and use of appropriate vehicle for delivery. This chapter discusses several such pre-clinical attempts to boost BCG with subunit vaccines tested in murine models and also highlights various recombinant TB vaccines undergoing clinical trials. Promising candidates include new generation of live recombinant BCG (rBCG) vaccines, VPM1002, which are deleted in one or two virulence genes. They encode for the mycobacteria-infected macrophage-inhibitor proteins of host macrophage apoptosis and autophagy, key events in killing and eradication of Mtb. These vaccines are rBCG- ΔureC::hly HM^R, and rBCG-ΔureC::hly ΔnuoG. The former vaccine has passed phase IIb in clinical trials involving South African infants and adults. Thus, with an aim of elimination of TB by 2050, all these cumulative efforts to develop a better TB vaccine possibly is new hope for positive outcomes.