Tuberculosis (TB) is the leading cause of death globally from a single infectious disease, and the only approved TB vaccine—BCG, which was introduced in 1921—has variable efficacy in adolescents and adults. As vaccination remains the most cost-effective method of controlling the disease, an improved vaccine for TB infection and disease prevention is expected to have a very large public health impact and has become a global priority. This project will support the IND-directed advancement of a novel TB vaccine in the form of a recombinant BCG strain that has an improved safety profile and the potential to provide greater protective efficacy that lasts into adulthood.