New mRNA Vaccine Shows Promise Against Tuberculosis

University of Sydney

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

A study into the vaccine's effectiveness, published in eBioMedicine, was led by experts from the Sydney Infectious Diseases Institute at University of Sydney, the Centenary Institute and the Monash Institute of Pharmaceutical Science (MIPS) at Monash University.

Currently the only approved vaccine for TB is the century-old Bacillus Calmette-Guerin (BCG) vaccine, which is widely used despite its effectiveness in adults being inconsistent.

The study found that the new mRNA vaccine was successful in triggering an immune defence response that helped to reduce TB numbers in infected mice. 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.

The vaccine used mRNA technology, which is where genetic instructions are used to trigger an immune response in the body, as opposed to using a weakened or deadened version of a virus.

Senior author Professor Jamie Triccas, Deputy Director of the Sydney Infectious Diseases Institute, said: "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."

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 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 (those that contain a weakened version of a pathogen), mRNA vaccines allow for rapid adaptation, making them an attractive option for global TB control efforts.

Dr Claudio Counoupas, co-lead author from the Centenary Institute's Centre for Infection & Immunity, highlighted the vaccine's potential impact: "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 COVID-19 but could be a game-changer for bacterial diseases like TB."

Professor Colin Pouton from Monash University, a key contributor to the study, explained: "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."

Following the study's promising results, the research 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," said Professor Triccas. "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."

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