New Vaccine Strategies to Improve, Boost, or Replace BCG

Over a century after it was first introduced, the live attenuated vaccine Bacille Calmette-Guérin (BCG) remains the only licenced vaccine against tuberculosis (TB). BCG is currently administered to more than 100 million children worldwide every year, yet the precise degree to which it protects against TB and the immune mechanisms underlying such protection remain unclear. While BCG is effective in some populations some of the time, overall, it has failed to control the global TB epidemic, and a more effective vaccine strategy is urgently needed. There are several viable pathways to a more effective TB vaccine represented in the current preclinical and clinical pipelines. These include improvements to BCG itself using genetic modifications to generate recombinant strains, administering BCG by different routes, or revaccination regimens that prolong the protective effects of BCG further into adolescence or adulthood. Alternatively, BCG may be boosted with heterologous subunit vaccines or be replaced altogether with live attenuated/inactivated strains of other mycobacteria or with DNA or RNA vaccines. In this chapter, we discuss each of these approaches and summarize current data on novel TB vaccines that aim to improve, boost, or replace BCG with a focus on the most promising candidates in preclinical development.