Antibodies are induced during natural infection with Mtb and in patients with TB disease, however, previous work from our team has shown that the antibodies are functional in only about 30% of infected individuals. Thus, just stimulating antibody production will not be sufficient to protect against disease, the antibodies generated also need to be functionally equipped. Our first aim is to understand the difference between protective and non-protective antibodies by comparing what they recognize, and how they interact with other components of the immune system to unravel what is essential for function and thus what is needed in terms of vaccine design. However, infection occurs at the mucosal surface, in the lung, and very little is known about the antibody responses that are present locally: in particular, their capacities to activate the immune system to control Mtb are unknown. Our second aim therefore will be to characterize the functional properties of antibodies at mucosal surfaces, a large knowledge gap.
We expect that the detailed characterization of these antibody responses will determine their role in fighting mycobacterial infections and will be critical to inform the rational design of novel vaccines.