How does genetic variation contribute to phenotypic fitness and vaccine efficacy in Mycobacterium bovis strains circulating in Algeria?

TB is a bacterial disease that impacts both humans and animals. It is caused by a particular group of bacteria that belong to the Mycobacterium tuberculosis complex (MTBC). While we have a vaccine (BCG) that is in current use in humans, it is over 100 years old and fails to protect against pulmonary TB in adults. Cattle also get infected with members of the MTBC that are adapted to animals to cause bovine TB (bTB). This causes huge productivity losses for the livestock industry and represents zoonotic risk to humans particularly in high-burden LMICs with less stringent biosecurity measures and lower economic capacity for expensive control programmes. 

Currently there is no vaccine for use in livestock, although BCG has potential, it shows variable levels of efficacy in expensive field trials. It has been suggested that strain diversity in the field influences efficacy, however we currently have a knowledge gap regarding strain diversity in animal adapted members of the MTBC and lack of tools in vaccine efficacy testing before new vaccines get to field trail stage. 

In this project will address these bottlenecks by using a high-throughput cost-effective assay that has been developed for use to test vaccines against the human-adapted MTBC. The project is pump-priming in nature as the assay has not been used against animal-adapted MTBC. We will examine efficacy against field strains isolated from Algerian cattle. We will also use innovative sequence technologies in these strains to discover antigenic diversity that may have been previously hidden due to geographical sampling bias and limitations of existing technologies. We hope this will lead to future use of the assay for testing novel vaccine candidates against clinically/field relevant circulating strains.