Ana Céspedes, Global Chief Operating Officer, IAVI
It may be hard to imagine, especially for younger generations, but until well into the 20th century, tuberculosis was one of the leading causes of death in Spain, surpassing by far other major causes of mortality such as syphilis or cancer. Several decades later, this infectious disease, as old as humanity itself, has become a global public health emergency. Its greatest burden of disease and mortality is concentrated in Asia and Africa, yet it continues to be a concern for high-income countries like Spain, where maintaining and strengthening control measures still require significant efforts in detection, intervention, and monitoring.
Since Robert Koch announced to the Physiological Society of Berlin in 1882 that he had discovered Mycobacterium tuberculosis, more than one billion people have died from tuberculosis—more than the combined deaths caused by HIV/AIDS, malaria, smallpox, cholera, plague, and influenza. In 2023 alone, 1.25 million deaths were attributed to tuberculosis. Most of these deaths occur among already vulnerable individuals, for whom the costs of treatment, combined with the inability to work and bring income home, perpetuate the cycle of illness and poverty, further limiting their chances to thrive.
From a health security perspective, drug-resistant tuberculosis adds more than 400,000 cases annually to the global epidemic of antimicrobial resistance, with only about 175,000 of these receiving proper diagnosis and treatment. The recently updated WHO list of «drug-resistant bacteria most dangerous to human health» has finally elevated drug-resistant tuberculosis to the highest priority level: «critical.» Although we now have better drugs to treat tuberculosis, options remain limited, and treatments are lengthy—a situation further complicated when dealing with resistant, or worse, multidrug-resistant strains.
The challenge of successfully detecting and treating tuberculosis, especially in resource-limited countries, means that for too many people, diagnosis or treatment comes too late—or not at all. Meanwhile, the slow and insufficient progress toward WHO tuberculosis control targets appears stalled or even reversed. With the current annual reduction rate of 2% in tuberculosis deaths, it is estimated that 31.8 million deaths will occur between 2020 and 2050, representing a cumulative economic loss of over $17.5 trillion.
Given this impact, it is imperative to maximize access to existing tools while accelerating the development of better ones, especially new vaccines capable of altering the trajectory of the global tuberculosis epidemic.
New Tuberculosis Vaccines: An Unprecedented Opportunity
The only vaccine currently available against TB remains the well-known and more than century-old BCG vaccine. While it can protect young children from severe forms of TB, it does not prevent pulmonary TB in adolescents and adults, who account for 90% of global cases and are the primary transmitters of the disease.
Without minimizing the scientific challenges of research and development (R&D) for new tuberculosis vaccines, it is clear that the greatest barrier to progress continues to be a chronic shortage of resources. TB vaccine R&D relies on a very small pool of donors and has never exceeded $120 million annually—500 times less than the annual investment in COVID-19 vaccine R&D and barely a tenth of the amount estimated to be necessary to close persistent funding gaps.
This funding shortfall is emblematic of the challenges affecting R&D for all so-called poverty diseases, with tuberculosis serving as a prime example. Essentially, the limited or uncertain profitability of these products means that, without adequate incentives, they fail to attract the private capital and expertise needed to complete development and ensure equitable production and distribution.
All of this makes it even more extraordinary to note that TB vaccine R&D is experiencing a moment of unprecedented promise and anticipation. On one hand, decades of persistence and scientific ingenuity have resulted in a pipeline of TB vaccine candidates which, though modest, for the first time includes several vaccines in advanced stages of R&D and others making progress in clinical development. On the other hand, the case for investing in TB vaccine R&D is now fully established and supported by extensive academic studies sponsored by the WHO, showing that the health, social, and economic impact would be measured in millions of lives saved and billions of dollars in savings.
Finally, and of critical importance, is the 2023 establishment by the WHO Director-General of a TB Vaccine Accelerator Council. Its mission is to facilitate the “development, approval, and use of new TB vaccines” and to bring together high-level political support for innovative and sustainable financing for R&D, as well as equitable access to vaccines once developed.
The Role of Public-Private Partnerships in Global Health R&D – The Case of the Spanish MTBVAC Vaccine
It is precisely in this context that promoting cross-sector collaboration for R&D becomes essential. This is the purpose for which organizations like IAVI were created—a nonprofit public-private partnership focused on the R&D of priority global health products, commonly referred to in English as a PDP, or «Product Development Partnership.»
IAVI focuses on establishing and leading R&D collaborations among the academic, biopharmaceutical, and philanthropic sectors, as well as with the countries and communities most affected, with the shared mission of turning R&D efforts into globally accessible products.
After more than 25 years of existence, and thanks to the philanthropic and public support of its donors, IAVI now has an R&D portfolio that includes antibodies and vaccine candidates for HIV, as well as vaccines for tuberculosis and several emerging infectious diseases classified as priorities by the WHO, such as Lassa fever.
One of the most promising and advanced candidates in this portfolio is MTBVAC, created by Professor Carlos Martín at the University of Zaragoza and currently being developed by Biofabri in collaboration with the Tuberculosis Vaccine Initiative (TBVI), the Indian biopharmaceutical company Bharat Biotech, and IAVI. At IAVI, we lead its clinical development for adults and adolescents, as well as the necessary resource mobilization efforts.
MTBVAC has particularly promising features, both in its design, which includes a broad repertoire of TB bacillus antigens that may confer greater immunogenicity, and in its administration, which involves a single-dose, adjuvant-free regimen, making it easier to produce and implement.
MTBVAC is currently in Phase 3 clinical trials for newborns in South Africa, Senegal, and Madagascar. IAVI is preparing to launch a Phase 2b efficacy trial in early 2025 across several sub-Saharan countries, while Bharat Biotech is conducting clinical trials in India.
The Phase 2b efficacy trial led by IAVI marks a critical stage in MTBVAC’s development. Involving thousands of participants and a multicenter structure, the trial demands enormous logistical and financial efforts to execute. The enthusiasm and anticipation of the research teams ahead of this imminent launch are aptly reflected in the name chosen for the trial: IMAGINE (an acronym for Investigation of MTBVAC Towards Accelerating Global Immunization for a Neglected Epidemic).
«If these trials show that MTBVAC is safe and effective, it could prevent millions of deaths, reduce the spread of drug-resistant TB strains, and save the economies and healthcare systems of affected countries billions of dollars, playing a central role in the global control of tuberculosis. What’s more, with the necessary resources, the relevant regulatory authorities have initially shown support for the idea of directly expanding the IMAGINE trial into a final Phase 3 trial, which could substantially reduce the overall time and cost of the R&D process and final product registration.
For this, a joint effort in funding R&D for new TB vaccines is essential, prioritizing the most advanced candidates and ensuring their fastest possible progress toward the finish line. Development cooperation agencies have a unique mandate to ensure R&D and global access to these products, as well as the expertise to assist low- and middle-income countries in the acquisition and distribution of new vaccines. Spain, the scientific and biotechnology birthplace of MTBVAC, has a unique opportunity to play a leadership role in this coalition of efforts to ensure an accelerated R&D push for new TB vaccines and their equitable, affordable global distribution once authorized.»