Developing next-generation tuberculosis vaccines based on pathogen–host interactions: Towards a holistic perspective

Tuberculosis (TB), caused by the highly complex intracellular pathogen Mycobacterium tuberculosis (Mtb), remains a leading burden on global health and the economy. Vaccines represent the most economically effective approach to preventing and controlling infectious diseases. Currently, Bacillus Calmette–Guérin (BCG) is the only available vaccine for TB, which protects infants and young children from disseminated and meningeal TB, but fails to provide effective protection against pulmonary TB in adults. Moreover, most of the candidate TB vaccines in preclinical stages or clinical trials have shown unsatisfactory effects due to poor efficacy and severe immunopathology. With the growing understanding of Mtb pathogenicity, it has been realized that the interactions between Mtb and the host are critical for determining TB disease outcomes and vaccine efficacy. Here, we review the progress and challenges in TB vaccine development and discuss recent advances in Mtb–host interactions, aiming to provide new strategies for developing next-generation TB vaccines based on pathogen–host interactions.