For over a century, the Bacillus Calmette-Guérin (BCG) vaccine has served as the world’s only available protection against tuberculosis (TB), a disease that continues to claim millions of lives. However, this long-standing vaccine is now on the verge of a significant transformation. On February 26, 2025, the International AIDS Vaccine Initiative (IAVI) and Biofabri, a subsidiary of Zendal, announced the administration of the first doses of the MTBVAC vaccine candidate in the IMAGINE phase 2 clinical trial in Paarl, South Africa. This development represents a major step forward in the fight against TB, particularly for underserved populations.
The IMAGINE trial is designed to evaluate the safety and efficacy of MTBVAC, a single-dose vaccine candidate aimed at preventing active tuberculosis lung disease in adolescents and adults. These age groups have historically been underserved by the existing BCG vaccine, which primarily offers protection to infants and young children. Unlike BCG, which provides only partial and short-lived immunity, MTBVAC aims to offer broader, long-term protection across different age demographics.
Participants in the trial will be monitored for two to three years to determine the vaccine’s effectiveness in preventing TB infections. If the results are positive, IAVI and Biofabri, along with other partners, plan to work together to ensure an affordable and sufficient supply of MTBVAC for low- and middle-income countries.
Despite medical advancements, TB remains the deadliest infectious disease worldwide. In 2023 alone, TB was responsible for approximately 1.25 million deaths, with cases reported in nearly every country. Alarmingly, TB cases have been increasing, including a resurgence in the United States in 2024.
The current BCG vaccine, first introduced in 1921, remains the only TB vaccine approved by the U.S. Food and Drug Administration (FDA). While it provides some level of protection estimated at about 50% in children it offers little to no defense for adolescents and adults. Given that TB primarily affects adults, there is a critical need for a more effective and universally protective vaccine.
Developing an improved TB vaccine has been a long-standing goal for global health organizations. IAVI highlighted in their announcement that an effective vaccine for all age groups could save millions of lives over time. If successful, MTBVAC would not only provide stronger protection but also contribute to controlling the spread of TB in high-burden areas.
“We are working towards the same common goal: the end of the devastating impacts of TB disease,” said Ana Céspedes, Pharm.D., MBA, and COO of IAVI. “We are honored to be part of this coalition to ensure an accelerated R&D push for a new TB vaccine and its equitable, affordable global distribution once authorized.”
As of early 2025, there are about 15 variations of the BCG vaccine used worldwide, with limited commercial availability in the United States. The introduction of MTBVAC could mark a turning point in global TB prevention efforts, potentially replacing the century-old BCG vaccine with a more robust and effective alternative.
With continued investment in research and international collaboration, the world is one step closer to reducing the burden of tuberculosis and moving toward the goal of global eradication.
