Novel mRNA vaccine shows potential against tuberculosis

Tuberculosis remains the number one cause of infectious mortality worldwide

A candidate mRNA vaccine that boosts immunity against tuberculosis (TB) has been shown to be effective in pre-clinical trials. It forms part of a successful collaboration between three leading Australian research institutions.

The team was drawn from the University of Sydney’s Infectious Diseases Institute, Centenary Institute in Sydney and Monash Institute of Pharmaceutical Science (MIPS) at Monash University in Parkville, Melbourne.

The more than 100-years-old Bacillus Calmette-Guerin (BCG) vaccine remains the only available inoculation against TB and is still widely used despite its effectiveness in adults being inconsistent.

TB is the leading cause of infectious mortality worldwide, responsible for approximately 1.3 million deaths annually, with a particular prevalence in countries such as India, Indonesia, Vietnam and Pakistan.

The study found the mRNA vaccine was successful in triggering an immune response that helped to reduce TB infection numbers in mouse models. In addition, the researchers discovered that for mice that had received the BCG vaccine, a booster dose of the new mRNA vaccine significantly improved their long-term protection.

mRNA technology uses genetic instructions to trigger an immune response as opposed to using a live-attenuated – weakened – pathogen or an inactivated pathogen vaccine.

 “Our findings demonstrate that an mRNA vaccine can induce potent, pathogen-specific immune responses that target TB, a disease that has long evaded effective vaccine development.

“This represents a major advance in TB vaccine research and provides a strong rationale for further clinical development,” said Professor Jamie Triccas, deputy director of the Sydney Infectious Diseases Institute, and the study’s senior author.

The researchers hope that the mRNA vaccine will ultimately be more effective and consistent than the BCG when used in humans. This is because, unlike protein-based or live-attenuated vaccines, mRNA vaccines allow for rapid adaptation, making them an attractive option for global TB control efforts.

 “mRNA vaccines offer a scalable, cost-effective and adaptable platform that can be rapidly deployed against infectious diseases. This study is an important step in demonstrating that mRNA technology is not just for [a viral infection like] COVID-19 but could also be a game-changer for bacterial diseases like TB,” said Dr Claudio Counoupas, co-lead author from the Centenary Institute’s Centre for Infection & Immunity.

 “The success of mRNA vaccines in the COVID-19 pandemic underscored their ability to generate strong immune responses. Our study provides the evidence that this platform can be harnessed for TB, potentially improving protection and durability of immunity in a way that traditional vaccines cannot,” added Professor Colin Pouton from Monash University.

Following the promising results of the study, the team is now looking to advance the vaccine to clinical trials.

“Our next goal is to refine the formulation and assess its efficacy in larger models before moving to human studies.”

“Given the global burden of TB and the limitations of current vaccines, we believe this platform could provide a new pathway toward eradicating this disease,” concluded Professor Triccas.

For further reading please visit: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00043-X/fulltext