Tuberculosis (TB) remains a worldwide health problem, causing around 2 million deaths per year. Despite the bacillus Calmette Guérin
vaccine being available for more than 80 years, it has limited effectiveness in preventing TB, with inconsistent results in trials. This highlights the urgent need to develop an improved TB
vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial
infection. Recent studies have revealed a potential role for autophagy, an intracellular homeostatic process, in
vaccine development against TB, through enhanced immune activation. This review attempts to understand the host innate immune responses induced by a variety of
protein antigens from Mycobacterium tuberculosis, and to identify future
vaccine candidates against TB. We focus on recent advances in
vaccine development strategies, through identification of new TB
antigens using a variety of innovative tools. A new understanding of the host-pathogen relationship, and the usefulness of mycobacterial
antigens as novel
vaccine candidates, will contribute to the design of the next generation of
vaccines, and to improving the host protective immune responses while limiting immunopathology during M.
tuberculosis infection.