BACKGROUND: Mycobacterium tuberculosis remains the largest infectious cause of mortality worldwide, even with over a century of widespread administration of the only licenced tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG). mRNA technology remains an underexplored approach for combating chronic bacterial infections such as TB. METHODS: We have developed a lipid nanoparticle (LNP)-mRNA vaccine, termed mRNA FINDINGS: Vaccination with mRNA INTERPRETATION: These findings of a protective LNP-mRNA vaccine for TB highlight the potential of the LNP-mRNA platform for TB control and support further research to facilitate translation to humans. FUNDING: This work was supported by the NHMRC Centre of Research Excellence in Tuberculosis Control to JAT and WJB (APP1153493), and MRFF mRNA Clinical Trial Enabling Infrastructure grant to CWP and HAW (MRFCTI000006).