A 100-Year-Old Tuberculosis Vaccine Won’t End TB: Why the World Needs a New Solution

Tuberculosis (TB) continues to be one of the most lethal infectious diseases globally, despite ongoing international efforts to combat it. A bacterium called Mycobacterium tuberculosis causes TB, which continues to threaten global health. In 2023, 10.8 million people became ill and 1.25 million lives were lost, according to the WHO Global TB Report 2024.¹ The need for a new, more effective tuberculosis vaccine is urgent, given the limitations of the existing Bacille Calmette-Guérin (BCG) vaccine. This article maps out why a new TB vaccine is needed, with a focus on drug-resistant, global burden, and limitations of the BCG vaccine.

Rising Public Health Threat of Tuberculosis 

Predisposing Factors 

People with weakened immune systems are more likely to develop tuberculosis if they become infected. This group includes people with HIV, individuals suffering from malnutrition, and those diagnosed with diabetes. Exposure to harmful substances like silica dust or indoor smoke also increases the risk. Frequent consumption of alcohol or tobacco can also impair the body’s immune system. All these factors make it harder for the body to fight TB, raising the chances of falling seriously ill after infection.²

Drug-Resistant TB

​The emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) represents an alarming global health threat. These strains do not respond to the most potent first-line anti-TB drugs, making treatment long, expensive, and difficult.² As of 2022, just 43% of individuals diagnosed with multidrug-resistant TB (MDR-TB) received proper treatment.³ A new vaccine could break the transmission cycle, reduce disease incidence, and indirectly curb the development of drug resistance by preventing new infections.

​High Global Burden and Unequal Impact

​TB predominantly affects people in low- and middle-income countries, with a disproportionate impact on vulnerable populations, including children and those with HIV.¹ The social and economic consequences are substantial, leading to loss of productivity and high treatment costs. A more effective vaccine could shift the focus from treatment to prevention, thereby reducing both the healthcare burden and socioeconomic fallout. The global burden of latent TB infection alone, estimated to affect 1.7 billion people in 2014, hitheghlights  massivea vast reservoir that  that could be addressed by a new vaccine could address.⁴

BCG vaccine limitations

The BCG vaccine, first introduced in 1921, remains the only authorized vaccine currently available for tuberculosis prevention. While it offers moderate protection against severe forms of TB in children, such as TB meningitis and miliary TB, it is largely ineffective in preventing pulmonary TB in adolescents and adults.⁵  This is a significant drawback, as adult pulmonary TB is responsible for the majority of global TB transmissions. Furthermore, the BCG vaccine’s effectiveness is inconsistent across different geographical locations, with its protection often waning over time.⁶

WHO End TB strategy

The WHO’s End TB Strategy targets a 90% reduction in tuberculosis-related deaths and an 80% decrease in new TB cases by the year 2030. If a new TB vaccine isn’t developed, it will be very difficult to achieve these important goals.Without a new vaccine, the WHO’s End TB targets will remain out of reach.² A vaccine that effectively protects adolescents and adults, who are the key transmitterstransmitte

New TB vaccine candidates (M72/AS01E, MTBVAC)

​Lessons from the COVID-19 Pandemic

​The COVID-19 pandemic, while disrupting global TB programs, also spurred unprecedented investment in vaccine technology and global health infrastructure. Significant progress has been made in vaccine technologies, including the development of mRNA-based approaches. These can help in developing a new TB vaccine. The COVID-19 pandemic also made people more aware of how important vaccines are. This presents a valuable opportunity to advance and promote the development of new TB vaccines.

​Challenges

​Despite progress, significant barriers remain. A key challenge in tuberculosis vaccine development is the lack of dependable biomarkers and the limited knowledge of how the immune system responds to Mycobacterium tuberculosis. The bacteria can remain dormant in the body for years without triggering symptoms, and immune responses differ greatly from person to person. This variability makes it difficult to create vaccines that are effective for diverse populations and suitable for all stages of the infection.⁶

Furthermore, clinical trials for TB vaccines are lengthy, costly, and logistically challenging due to the slow progression of the disease. Additionally, political will, equitable distribution, regulatory approvals, and public acceptance will be crucial for success.⁶  Vaccine hesitancy, lack of manufacturing capacity, and intellectual property concerns could slow rollout. Global partnerships, especially between public institutions and private biotech companies, will be essential to navigate these hurdles.

​Conclusion

​The global TB crisis cannot be solved with 100-year-old tools. While the BCG vaccine has saved millions of lives, its limitations in preventing pulmonary TB among adults make it inadequate for current challenges. With drug-resistant TB on the rise and the global burden remaining high, a new, more effective vaccine is critical. 2025 must be a turning point. With several promising candidates in late-stage development and increased global collaboration, the world has a historic opportunity to change the trajectory of the TB epidemic. A successful new vaccine could be the missing piece in the global fight to finally end tuberculosis.

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