Tuberculosis vaccine: A journey from BCG to present

Tuberculosis (TB) is the leading cause of death worldwide due to an infectious disease, causing around 1.6 million deaths each year. This situation has become more complicated by the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) and HIV-TB co-infection, which has significantly worsened TB prognosis and treatment. Despite years of intensive research, Bacille Calmette-Guerin (BCG) remains the only licensed vaccine and has variable efficacy. It provides protection against childhood TB but is not effective in adult pulmonary TB. As a result of intense research in understanding TB vaccinology, there are many new vaccine candidates in clinical development and many more in pre-clinical trials which aim either to replace or boost BCG vaccine. This review discusses the history of BCG vaccine development and summarizes limitations of the current vaccine strategy and recent advances in improving BCG immunization along with other new vaccines in clinical trials which are promising candidates for the future tuberculosis vaccinology program.