Inhaled TB Vaccine: A Path to Global Elimination?

Tuberculosis (TB), a disease largely considered a relic of the past in developed nations, remains a global health crisis, infecting a quarter of the world’s population. While the existing Bacillus Calmette-Guérin (BCG) vaccine offers protection to children, its efficacy wanes in adults – the demographic most vulnerable to severe disease and transmission. Now, Australian researchers are making headway in understanding *why* the BCG vaccine fails in adults, and crucially, how to engineer a more effective, long-lasting immunity, potentially through a surprisingly familiar route: direct delivery to the lungs.

The story of TB vaccination is marked by unintended consequences. Originally intended for oral administration in the 1920s, the BCG vaccine was switched to intradermal injection following a tragic incident in Lübeck, Germany, where a contaminated batch caused severe illness and death. However, recent research suggests the original route of administration may have been key to its effectiveness. The current study builds on a 2019 Nature publication demonstrating near-complete protection against TB in macaques when BCG was delivered intravenously – a route obviously unsuitable for widespread human use. This led researchers to explore mucosal delivery, specifically to the lungs, as a more practical alternative.

Associate Professor Andreas Kupz and his team have demonstrated that a slightly more potent version of BCG, when delivered directly to the lungs, triggers a more robust and sustained immune response. This isn’t simply about creating a stronger initial immune reaction; it’s about establishing a population of long-lived T cells *within* the lungs, the very site of infection. This localized immunity is critical, as TB primarily attacks the respiratory system. The research points to the importance of activating progenitor cells in the lungs, which then differentiate into these protective T cells.

The implications extend beyond vaccine development. The resurgence of TB deaths during the COVID-19 pandemic, coupled with the rise of multi-drug resistant strains – particularly in hotspots like Papua New Guinea – underscores the urgent need for improved control measures. The Torres Strait Treaty, facilitating movement between PNG and Australia, highlights the biosecurity challenges and the responsibility Australia has to both its neighbor and its own vulnerable communities, particularly First Nations populations who experience TB infection rates 5-6 times higher than the non-Indigenous population. Addressing TB isn’t just a public health imperative; it’s a matter of equity and social justice.

The Forward Look

While promising, the path to a more effective TB vaccine isn’t without hurdles. The current research utilizes genetically modified BCG strains that aren’t yet approved for human use. However, ongoing clinical trials at Oxford University are evaluating the safety and immunogenicity of BCG delivered directly into the lungs using the licensed 1921 strain. The results of these trials, expected in the coming months, will be pivotal in determining whether mucosal delivery can be translated into a viable vaccination strategy. Furthermore, Associate Professor Kupz’s team has developed a modified BCG strain that induces better immunity without the increased virulence of the initial experimental strains, offering a potential solution to safety concerns. The biggest challenge remains funding; sustained investment is crucial to accelerate research and development in this often-overlooked disease. If mucosal BCG vaccination proves successful, it could represent a paradigm shift in TB prevention, finally offering the prospect of a truly effective, long-lasting vaccine against the world’s largest infectious killer.