Targeting tuberculosis with LNP-mRNA vaccines: opportunities, challenges and future directions

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality, despite widespread use of the Bacillus Calmette–Guérin (BCG) vaccine. The COVID-19 pandemic demonstrated the potential of mRNA vaccines to induce rapid and robust immunity, leading to interest in their application against TB. However, developing an effective mRNA vaccine for TB presents unique challenges, including the need for strong cellular immune responses and lung-targeted immunity. This review explores the potential of lipid nanoparticle (LNP)-encapsulated mRNA vaccines to generate protective immune responses against Mycobacterium tuberculosis. We discuss recent advances in the field, including promising preclinical studies, and highlight key knowledge gaps that must be addressed before mRNA vaccines can be considered a viable option for TB control.