A Crisis Hiding in Plain Sight

While the world fixated on COVID-19, another pandemic raged on in silence. Tuberculosis (TB) remains the leading infectious cause of death globally, killing 1.3 million people every year—more than HIV/AIDS and malaria combined. Yet the only widely available TB vaccine, Bacillus Calmette-Guérin (BCG), was first administered in 1921 and has changed little since. It provides some protection to infants but offers inconsistent efficacy in adults—the very group most at risk of severe disease and transmission.

For over a century, TB has remained a disease of inequality. The global health community knows how to treat it, yet millions still die. The BCG vaccine is a relic of outdated science, and global funding for TB research lags far behind that of other infectious diseases. Meanwhile, the emergence of antibiotic-resistant TB strains threatens to push the disease further beyond the reach of treatment. The world needs a new weapon against TB—urgently.

Now, scientists in Australia believe they’ve found one. A research team from the University of Sydney’s Sydney Infectious Diseases Institute, the Centenary Institute, and Monash University has developed an mRNA-based vaccine that, in preclinical trials, has triggered strong immune responses and reduced TB bacteria in infected mice. If successful in humans, this vaccine could overhaul TB prevention on a global scale. Findings from the new study were published recently in eBioMedicine.

The Power of mRNA: A Post-COVID Revolution

The COVID-19 pandemic showcased the power of mRNA vaccines: rapid development, strong immune response, and the ability to be adapted for evolving pathogens. But could the same approach work for TB, a notoriously stubborn bacterial disease?

The team’s study suggests the answer is yes. Unlike traditional protein-based or live-attenuated vaccines, mRNA vaccines work by delivering genetic instructions that teach the body to produce pathogen-targeting proteins. In preclinical tests, this mRNA vaccine stimulated an immune defense that significantly reduced TB bacterial loads in mice. Even more promising, when used as a booster for mice that had previously received the BCG vaccine, the new shot dramatically enhanced long-term immunity.

“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,” said Professor Jamie Triccas, Deputy Director of the Sydney Infectious Diseases Institute. “This represents a major advance in TB vaccine research and provides a strong rationale for further clinical development.”

A Global Health Turning Point?

The urgency of a TB vaccine breakthrough cannot be overstated. TB thrives in conditions of poverty, overcrowding, and poor healthcare access. It disproportionately affects populations in South Asia, Africa, and parts of Latin America—regions where BCG’s inconsistent protection leaves millions vulnerable.

And the situation is worsening. Multidrug-resistant TB (MDR-TB) is spreading, making treatment options increasingly ineffective. The World Health Organization (WHO) has warned that without new interventions, TB deaths could rise in the coming decades.

“mRNA vaccines offer a scalable, cost-effective, and adaptable platform that can be rapidly deployed against infectious diseases,” said Dr. Claudio Counoupas, co-lead author from the Centenary Institute’s Centre for Infection & Immunity. “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, another key contributor to the study, reinforced the potential impact: “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.”

The Road to Clinical Trials—and the Political Hurdles Ahead

The next challenge is turning this laboratory breakthrough into a real-world vaccine. The research team is refining the formulation and preparing for large-scale trials, which will be critical in determining the vaccine’s safety and efficacy in humans.

But even if the science holds up, there’s another battle to fight: funding and distribution. Unlike COVID-19 vaccines, which received unprecedented financial backing, TB vaccines have historically been underfunded, largely because the disease primarily affects lower-income nations. Without major investment from global health organizations, governments, and pharmaceutical companies, even the most promising TB vaccine could remain stuck in development limbo.

“Our next goal is to assess its efficacy in larger models before moving to clinical trials,” 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.”

Will the World Act?

The science is clear: a new TB vaccine is not just possible—it’s within reach. The question now is whether the world has the political and financial will to make it happen.

TB has been the silent pandemic for far too long. If we’ve learned anything from COVID-19, it’s that when the world prioritizes infectious disease threats, solutions emerge. The new mRNA vaccine for TB offers a long-overdue opportunity to rewrite the history of one of humanity’s oldest and deadliest diseases. But only if we act now.