BCG: Past, Present and Future Direction

Bacillus Calmette-Guérin (BCG) is a live-attenuated vaccine developed over 100 years ago and remains the only vaccine ever licensed in the fight against tuberculosis (TB). It is one of the most widely used vaccines in the world, having been administered to over four billion people, with another 100 million children vaccinated with BCG every year. Despite this, significant debate exists surrounding its efficacy against TB and its place in routine infant vaccination schedules. Severe side effects following BCG administration are rare but may be seen in those with immune system dysfunction. Safer vaccines for use in these individuals would be valuable. BCG has been shown in some studies to have beneficial effects on mortality and morbidity beyond that attributable to reduction in TB alone. Understanding the immunological mechanisms underpinning these non-specific effects is increasing and appears in part to be due to the induction of trained innate immunity. New vaccines developed against TB will either need to be given as a booster following initial BCG vaccination or be shown to be non-inferior with regard to these off-target effects. Despite its age, widespread usage, and intensive study, we are still learning how BCG exerts its effects and unpicking what these really are. Alternative routes of administration and recombinant forms of BCG offer promising strategies to further harness the potential of this intriguing vaccine.