Jayne Sutherland: Analysis of protective immunity to Mycobacterium tuberculosis in the lung and blood of exposed household contacts in The Gambia

Analysis of protective immunity to Mycobacterium tuberculosis in the lung and blood of exposed household contacts in The Gambia

Tuberculosis (TB) remains the leading cause of death from a single pathogen with over one million deaths per year. The only licensed vaccine, Bacillus Calmette-Guérin (BCG) is over 100 years old and does not provide protection from adult pulmonary TB. However, in order to develop more effective vaccines, we need to understand what constitutes protective immunity to the causative pathogen, Mycobacterium tuberculosis (Mtb). This requires analysis of longitudinal cohorts of household contacts (HHC) recently exposed to a newly diagnosed TB patient to identify individuals protected from infection and those protected from disease (or both). We have previously identified a Type I interferon signature using whole blood RNA sequencing, that was enriched in Mtb infection ‘resisters’. Building on these findings, we have now gone beyond the blood to analyse the site of infection using broncho-alveolar lavage. Together with recent technologies such as single cell sequencing we aim to better define cell types and signatures involved in protection against both infection and disease. These results could provide novel avenues for rational development of effective vaccines.