Momentum of hope: The journey toward a universal TB vaccine

Sir,

Mycobacterium tuberculosis (Mtb), responsible for tuberculosis (TB), stands prominently as a principal driver of morbidity and mortality, especially in lower-income nations. ¹ Globally, the spectre of TB intertwines deeply with socio-economic disparities, positioning its control at the intersection of equity and human rights. In regions grappling with a heightened TB burden, conventional control measures are strained, further exacerbated by the concurrent surge in TB cases. ¹ Over a century ago, the narrative of this menacing disease began to shift. Within the confines of the Pasteur Institute in Lille, France, Albert Calmette and Camille Guérin embarked on a groundbreaking journey. ² Through meticulous cultivation of Mycobacterium bovis, a cattle strain of the bacterium, over 13 years work and 230 subcultures, they birthed a less virulent strain. ² The year 1921 marked a pivotal moment when a newborn, tragically orphaned by TB, became the vaccine's inaugural human recipient. This success spawned an era of mass immunisation, with millions receiving the vaccine by the 1930s. ³

Modern iterations of this vaccine, derivatives of attenuated strains of M. bovis, are administered intradermally. Their ubiquity, especially in high TB burden countries where they reach over 80% of newborns, underlines their undeniable significance. ¹ Yet, while they have been instrumental in shielding many, their efficacy is not absolute. A recent study published in 2022 elucidated these nuances; the BCG vaccine offers robust protection against TB for children under five but diminishing in older children and adults. ⁴ Compounding this challenge, the vaccine does not protect against M. tuberculosis infection, thus allowing the bacterium's continued transmission.

To quell this persisting threat, the WHO's ambitious End TB Strategy envisions a transformative landscape: an 80% reduction in TB incidence and a 90% plummet in TB mortality by 2030. ⁵ Achieving this necessitates vaccines effective both before and after exposure. Among the vibrant tapestry of prospective vaccines, the M72/AS01E (M72) shines with promise. ³ This protein subunit vaccine melds two M. tuberculosis antigens with the adjuvant system AS01E, augmenting the immune response. Preliminary data from Phase 2b trials are encouraging, revealing its 50% efficacy against pulmonary TB in adults with latent infection. ⁶ Bolstered by the backing of renowned institutions such as the Wellcome and Bill & Melinda Gates Foundation, this vaccine is now poised for further exploration in Phase 3 trials. ³ Other innovative candidates such as VPM1002 and MTBVAC, rooted in genetically modified strains of the bacterium, also suggest optimism. The former, using a modified M. bovis strain, ensures enhanced immune recognition, while the latter, anchored in the human TB bacterium, promises a broader immune response. ³

As the world stands at this significant juncture, a little over a century since the maiden BCG administration, the path forward is tinged with both challenge and hope. With the momentum of hope guiding the journey towards a universal TB vaccine, the scales in this age-old battle against an ancient pathogen may finally be tilting in humanity's favour.