The World Health Organisation considers the development and implementation of new TB vaccines to be a top priority as vaccines are increasingly recognized as highly effective tools to mitigate antibiotic resistance. We recently developed Galsomes, mRNA based nanovaccines that upon intramuscular injection, specifically target immune cells to which they simultaneously deliver antigen encoding mRNA as well as glycolipids. As a result, they manage to engage multiple immune effector cells and induce innate (iNKT, NK cells) as well as adaptive immunity (humoral and cellular). This project aims to further explore the potential of the Galsome vaccine for intracellular bacterial infections, in particular tuberculosis (TB). At first we want to optimise the mRNA construct to provide improved cellular immunity. Subsequently Galsome induced immunity will be explored by defining the optimal combination of different well-known TB related antigens. In addition we will make use of a recently implemented immunopeptidomics pipeline for the detection of antigenic peptides presented by bacteria infected cells. Finally, we will perform a prophylactic vaccination study in a relevant preclinical model of active TB with the most optimal Galsome formulation.