Tuberculosis (TB), caused by the infectious agent Mycobacterium tuberculosis, remains a leading cause of death worldwide and was responsible for an estimated 1.3 million deaths in 20221. While the current vaccine, known as BCG, protects against TB in young children its effectiveness quickly wanes meaning adults remain largely unprotected, necessitating the development of novel vaccines2. Subunit vaccines are a well-established vaccination strategy to deliver highly immunogenic antigens coupled with a strong safety profile. While this strategy exposes the immune system to less antigens than BCG vaccination, rational selection of antigens from various stages of Mtb infection can generate a robust cellular immune response, critical for infection control. Here we have investigated subunit vaccines delivered as nucleic acids against TB using two approaches, DNA and mRNA. DNA vaccines have proved useful tool to determine the immunogenicity and protective efficacy of potential vaccine candidates expressed in vivo. Immunogenicity studies have been conducted to determine the cellular immune response to vaccination with plasmid DNA encoding for membrane proteins from Mtb, and the protective efficacy of these constructs was tested in a murine model of TB. While DNA vaccination did not provide protection it did promote the generation of antigen-specific cellular immunity as measured by IFN-γ ELISpot, this allowed for the selection of critical antigens from key stages of the infectious lifecycle of Mtb (colonisation; esat6, persistence; SERoM1, and reactivation; RpfE) and to move forward into trials with mRNA. We have obtained mRNA through our collaboration with Moderna encoding our leading antigens and confirmed their expression in mammalian cell line. Subsequently these antigens have been formulated with lipid nanoparticles for use in vaccine efficacy trials.