Lay summary
The Tuberculosis (TB) vaccine, BCG, is the world’s most widely administered vaccine, yet we do not know how its partial protection works. Previously, I have recruited a cohort of TB cases and their household case contacts in Indonesia. Among 1350 contacts, 25% are persistently infection test negative despite heavy exposure. I found that these ‘early clearers’ are much more likely to have had BCG vaccination and have stronger innate immune responses than those who develop an infection. It is likely that BCG induces protection by promoting epigenetic changes that boost innate immunity. This proposal is to recruit new participants to the cohort to identify epigenetic markers of BCG protection from M. tuberculosis. This study will assist the development of better vaccines by advancing our understanding of protective immunity to M. tuberculosis and potentially provide a marker of protection for use in future clinical trials.