The world urgently needs an effective tuberculosis (TB) vaccine to reduce the illness and death caused by this centuries-old bacterium. As World TB Day is observed, a promising experimental TB vaccine is undergoing testing at a study site in Paarl as part of a large-scale, multi-country clinical trial.
On February 19, the first dose of an experimental TB vaccine called MTBVAC was administered at a clinical trial site in Paarl. Along with another promising experimental vaccine, M72, MTBVAC represents a major step in the global fight against TB. Although TB is curable, diagnosis and treatment remain challenging, making TB the leading infectious disease killer caused by a single agent. It claims around 1.5 million lives annually, with over 50,000 of those deaths occurring in South Africa.
Despite the availability of the Bacillus Calmette-Guérin (BCG) vaccine, which is over a century old, it only provides partial protection against TB disease in children. To turn the tide against TB, experts agree that a more effective vaccine is needed. Research funders have recently supported large clinical trials to determine whether newer experimental vaccines can outperform BCG.
One of these large-scale trials, the IMAGINE study (Investigation of MTBVAC toward Accelerating Global Immunization for a Neglected Epidemic), aims to enroll 4,300 participants, making it the largest trial of MTBVAC to date. The trial is being conducted at 12 sites in South Africa, with additional sites in Kenya and Tanzania. The Mbekweni research center in Paarl was chosen for its high TB prevalence and has previously hosted HIV and COVID-19 trials.
Dr. Lize Hellström, principal investigator at the Be Part clinical research center in Mbekweni, explained that the first vaccination of MTBVAC (or a placebo) in the entire three-country trial took place there on February 19. The center began preparing for the trial in June 2023, securing funding from the Gates Foundation, Open Philanthropy, and the German government, as well as partnering with the International AIDS Vaccine Initiative (IAVI).
If MTBVAC proves effective, Biofabri, the company developing the vaccine, has committed to ensuring an affordable and sufficient supply for low- and middle-income countries. CEO Esteban Rodriguez confirmed that Biofabri and its partners in Asia and South America will collaborate to achieve this goal.
The study is focusing on individuals with latent TB infection—those who carry the TB bacterium in their lungs but do not have active TB disease. Around 10% of people with latent TB develop TB disease. Participants in the study receive either the MTBVAC vaccine or a placebo, and researchers will monitor TB rates over time to determine the vaccine’s effectiveness. The trial aims to reach 35 TB cases across all sites to assess the vaccine’s protective effects.
MTBVAC is a live-attenuated vaccine derived from the TB bacterium. It contains a weakened version of the bacterium, designed to trigger an immune response without causing illness. Unlike M72, which requires two doses, MTBVAC is administered as a single shot. Researchers hope it will provide at least 50% protection for both adults and children.
Professor Keertan Dheda, Principal Investigator at the University of Cape Town, highlighted the difficulties in developing a TB vaccine. Unlike COVID-19, TB lacks reliable animal models for testing, and researchers are still uncertain about the precise immune responses required for protection. To maximize the chances of success, multiple vaccine candidates are being tested simultaneously.
If MTBVAC is successful, it could save lives, prevent severe lung disease, and have a positive economic impact, particularly in TB-endemic countries like South Africa. While the IMAGINE trial is a phase 2b study, other trials are testing MTBVAC in neonates at the phase 3 level. Vaccines typically receive regulatory approval after proving safety and efficacy in phase 3 trials.
Another TB vaccine candidate, M72, has shown about 50% efficacy in phase 2 trials and is now undergoing a massive phase 3 trial. Unlike MTBVAC, M72 requires two doses given a month apart. Researchers remain hopeful that at least one of these vaccine candidates will provide the breakthrough needed in the fight against TB.
At the Mbekweni site, the atmosphere is one of commitment and determination. The research center, which began as a small facility in 2005, has grown into a well-equipped institution with a team of 42 professionals, including doctors, nurses, and data technicians. Trial participants, described as the “true heroes” of the study, have volunteered to contribute to groundbreaking research that could benefit future generations.
Dr. Elana van Brakel, IAVI’s Medical Director, emphasized that many participants see their involvement as a way to bring about change. They may not personally benefit from the trial, but they recognize its potential to protect their children and communities. The trial’s success could mark a turning point in the fight against TB, particularly for those living with HIV, as TB remains the leading cause of death among HIV-positive individuals.
With ongoing clinical trials and increasing investment in TB research, the hope is that a more effective vaccine will soon become available, offering new protection against a disease that continues to claim millions of lives worldwide.
