Factors influencing the efficacy of Bacille Calmette-Guérin (BCG) vaccine

The considerable scope of the worldwide tuberculosis (TB) crisis and the emergence of antibiotic-resistance have spurred efforts to develop new TB vaccines, albeit without success (Scriba, Netea et al., 2020). Bacille Calmette-Guerin (BCG) remains the only licensed TB vaccine which protects against disseminated forms of TB in infants and young children (Rodrigues, Diwan et al., 1993, Trunz, Fine et al., 2006, Barreto, Pilger et al., 2014). However, the burden of TB is highest in adults in whom the efficacy of BCG is significantly variable (Colditz, Brewer et al., 1994). Recently, more resources have been channelled towards improving the efficacy of the century old BCG vaccine in adults and developing novel subunit vaccines for TB or developing vaccine strategies that incorporate BCG to retain its protective effect (Skeiky and Sadoff 2006, Hawkridge, Scriba et al., 2008, Lienhardt, Fruth et al., 2012, Monin, Griffiths et al., 2015). Distinct studies have identified several factors that are attributed to the variable protection conferred by BCG in different populations (Brosch, Gordon et al., 2007, Anderson, Webb et al., 2012). To improve the current efficacy of BCG requires thorough understanding of protective vaccine induced immune responses following immunization with BCG. Here we review the factors which contribute towards interindividual variability to the BCG vaccine in various demographics. These factors are heterogenous and understanding their cumulative effect on TB immunity has the potential to impact the implementation of TB vaccine programmes in endemic settings and result in more robust correlates of protection which could potentially curb the scourge of TB.