Tuberculosis (TB) is the number one cause of infectious mortality worldwide, despite treatments being widely available. A new vaccine breakthrough may provide the mechanism to reduce the infectivity rate of this ancient bacterial disease. The vaccine is at the pre-clinical trial stage.
The candidate vaccine is part of a successful collaboration between three leading Australian research institutions: Sydney Infectious Diseases Institute at University of Sydney, the Centenary Institute and the Monash Institute of Pharmaceutical Science (MIPS) at Monash University.
Remarkably, the only approved vaccine for TB is the century-old Bacillus Calmette-Guerin (BCG) vaccine. This vaccine contains a weakened form of the Mycobacterium bovis bacteria, which is closely related to the bacteria that cause TB. The vaccine helps the immune system recognize and fight off TB bacteria if exposed in the future. It happens to be the most widely used vaccine on the planet, with more than 4 billion doses delivered. Yet BCG is an imperfect vaccine that wanes in effectiveness as children age into adolescence.
The vaccine is based on mRNA technology, where genetic instructions are used to trigger an immune response in the body, as opposed to using a weakened or deadened version of an infectious agent.
mRNA vaccines are a type of vaccine that use messenger RNA (mRNA) to instruct cells to produce a protein that triggers an immune response. This immune response helps the body recognize and fight off the actual virus or pathogen if it encounters it in the future.
The study demonstrated that a new mRNA vaccine was successful in triggering an immune defence response that helped to reduce TB numbers in infected mice.The researchers also discovered that for mice that had received the BCG vaccine, a booster dose of the new mRNA vaccine significantly improved their long-term protection.
Senior author Professor Jamie Triccas, Deputy Director of the Sydney Infectious Diseases Institute, explains further: “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.”
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.
mRNA vaccines offer the ability to be a scalable, cost-effective, and adaptable platform in a form that can be rapidly deployed against infectious diseases.
The research team is looking to advance their vaccine to clinical trials.
The research appears in the journal eBioMedicine, titled “An LNP-mRNA vaccine modulates innate cell trafficking and promotes polyfunctional Th1 CD4+ T cell responses to enhance BCG-induced protective immunity against Mycobacterium tuberculosis.”
