Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide with approximately 1.5 million deaths annually. Furthermore, it is estimated that up to two billion people are latently infected with Mycobacterium tuberculosis, the causative agent of TB. The only licensed TB vaccine, Bacille Calmette–Guérin (BCG), which is universally used to prevent TB in children since 1921, has low efficacy against TB in adults and is not recommended for people with impaired immunity. Despite extensive research efforts for a century, most new TB vaccine candidates have not shown superior efficacy over BCG, and the development of a rationally designed BCG-replacement vaccine remains crucial.
In my presentation, I will discuss our latest results and ongoing projects regarding the further development and pre-clinical evaluation of the recombinant BCG strain, BCG::ESAT6-PE25SS. I will cover the foundational studies that have led to the rational design of the vaccine candidate and will provide data demonstrating how this strain uncouples virulence from immunogenicity. I will show data regarding the superior safety and efficacy of the vaccine candidate in several pre-clinical animal models of TB, including mouse and rabbit models of type 2 diabetes and reactivation of latent TB. My presentation will also touch on results showing reduced mycobacterial meningoencephalitis after infection of severely immunocompromised mice and increased T cell activation in the lung following mucosal vaccine administration. Furthermore, I will provide insights into an ongoing global head-to-head tournament designed to compare our vaccine to 5 other leading TB vaccine candidates from around the world. Finally, my presentation will outline the final steps required to complete pre-clinical evaluation and process optimisation leading towards future human trials.