Abstract
Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (Mtb), is a significant burden on global public health. There is an immediate need for a new, effective vaccine for TB as the current Bacille Calmette-Guérin (BCG) vaccine fails to provide long-term protection beyond childhood. The development of new vaccines for TB have been hampered by limited knowledge surrounding immune correlates of protection against Mtb infection. Case contact studies of TB in high incidence regions have identified that a proportion of individuals do not develop Mtb infection despite high exposure to the pathogen, in a phenomenon known as early clearance. An incomplete understanding of this protective response to Mtb infection currently exists. However, the involvement of unconventional T cells and trained innate immunity induced through BCG vaccination is hypothesised as an underlying mechanism for this host resistance. The present study aims to identify cell populations involved in the early clearance of Mtb through the analysis of whole blood samples from household contacts of active TB cases in Bandung, Indonesia, collected as part of the Innate Factors in Early Clearance of Mtb (INFECT) study. Optimisation and unsupervised high dimensional analysis of a dataset of unstimulated blood samples from household contacts of TB cases implicated CD8, MAIT, and Vδ2+ T cells in early clearance in the INFECT cohort. Alongside this, a multiparameter flow cytometry panel was developed and optimised to explore the production of effector proteins from stimulated whole blood samples from the INFECT cohort. By adding to the current understanding of early clearance, it will be possible to identify immune correlates of protection against Mtb infection. Immune targets, such as those identified in this study, could be used in the development of new vaccines for the prevention of Mtb infection.