mRNA vaccines have transformed the field of infectious disease prevention, with their success against SARS-CoV-2 generating interest in expanding this technology to other pathogens. Despite this, the potential of mRNA vaccines in controlling complex intracellular bacteria remains underexplored. Mycobacterium tuberculosis is the leading cause of death from a single infectious agent, with over 10 million cases and 1 million deaths reported in 2023 alone. This ongoing crisis reflects the limited protection provided by the current tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), and represents an opportunity for the mRNA vaccine platform. We have previously demonstrated that a novel mRNA vaccine, formulated with the standard ‘Onpattro’ lipid nanoparticle (LNP) and encoding a fusion of immunogenic M. tuberculosis antigens Ag85B and CysD, elicits strong immune responses and confers pulmonary protection against M. tuberculosis in mice. The mRNA sequence in this construct was codon optimised to reduce uridine content, constructed using N1-methyl-pseudoUTP, and contains a SEAP signal peptide. To improve the efficacy against M. tuberculosis we have formulated additional constructs with modifications to two components of the mRNA vaccine platform. Firstly, expanding the antigenic repertoire of the mRNA sequence by co-administering with additional constructs that encode for a further five M. tuberculosis proteins. Secondly, adjusting the molar ratio of lipids comprising the LNP used for in vivo delivery of the mRNA construct to redistribute the biodistribution and translation of the mRNA sequence. C57BL/6 mice were immunised with 3 doses of each vaccine formulation before infection with a low dose of aerosol M. tuberculosis. Multiparameter flow cytometry staining of the blood, spleen and lungs revealed that all LNP formulations induced potent CD4+ T cells producing IFNγ, IL-2, and TNF, which are considered essential for controlling M. tuberculosis infection. Furthermore, each individual M. tuberculosis antigen encoded in the mRNA constructs were able to induce these responses. Following infection with aerosolised M. tuberculosis, all LNP-mRNA vaccinated mice significantly reduced bacterial load in the lungs compared to naïve controls. However, only the mRNA vaccine construct formulated with a unique LNP formulation containing less PEGylated lipid conferred significant protection against disseminated M. tuberculosis infection in the spleen. These findings highlight the utility of the mRNA vaccine platform beyond viral pathogens and provide insight into the design of mRNA-based therapeutics targeting intracellular bacteria such as M. tuberculosis.