The world desperately needs an effective TB vaccine to reduce the illness and death still being caused by the centuries' old bacterium. As we mark World TB Day, Spotlight visited a study site in Paarl where a promising experimental TB vaccine is now being tested as part of a large multi-country clinical trial.
The first dose of an experimental tuberculosis (TB) vaccine was administered on February 19 at a clinical trial site in Paarl. The vaccine called MTBVAC, along with other experimental vaccines, most notably one called M72, is carrying the hopes of many in the TB world.
While TB can be cured, diagnosis and treatment is often tricky - so much so that TB is the world's top infectious disease killer from a single agent. It claims in the region of 1.5 million lives a year, of which over 50 000 are in South Africa.
To definitively turn the tide on TB, many experts concur we will need an effective vaccine. The one TB vaccine we do have, Bacillus Calmette Guérin (BCG), is over a hundred years old and only offers partial protection against TB disease in children. Research funders have in recent years backed some of the large clinical trials needed to figure out whether new experimental vaccines can do better.
The IMAGINE study
One of those large clinical trials is called IMAGINE, which stands for Investigation of MTBVAC toward Accelerating Global Immunization for a Neglected Epidemic. With a projected 4 300 study participants, it is set to be the largest study so far of MTBVAC.
Spotlight last week visited the vibrant Be Part clinical research centre (CRC) in Mbekweni, Paarl, where the first shots were administered in the study. It is one of 12 trial sites in South Africa, with two more in Kenya and one in Tanzania.
The Mbekweni site, nestled in the valley between Paarl Mountain and the Drakenstein mountain range, was chosen because of the area's very high TB rates. Multiple HIV and COVID-19 trials have previously been run at the site.
Speaking to Spotlight at the Be Part CRC office, Dr Lize Hellström, principal investigator and founder of the 20-year-old centre, says the first vaccination of MTBVAC (or a saline placebo) was administered to their first triallist on February 19 this year - the first in the entire three-country trial.
"It was an exciting moment. Our prep began in June 2023 when we managed to get Gates Foundation and Open Philanthropy funding and partner with the International AIDS Vaccine Initiative (IAVI) - a non-profit public-private product development outfit," says the veteran HIV clinician. The trial is also funded by the German Government.
If MTBVAC is shown to be efficacious, Biofabri (the company making the vaccine), IAVI, and other partners say they will work together to ensure there is a sufficient, affordable supply of MTBVAC available for low- and middle-income countries. "Biofabri and its partners in Asia and South America will work together ensure this," says Esteban Rodriguez, CEO of Biofabri.
Testing in people with latent TB
Back at the Mbekweni site, Hellström says: "we are now at 62 people screened and 18 vaccinated here (the goal being 287 vaccinated per site), meaning we've completed the blood tests to narrow candidates down to those who've previously had exposure to the TB bacterium but have not developed TB disease."
The trial is focusing on preventing disease in people who have latent TB infection, that is to say have the bug in their lungs, but who are not ill with TB disease. Only around 10% of people with latent TB infection end up falling ill with TB disease.
In short, one group of study participants are receiving the MTBVAC jab while another group are receiving a placebo. The researchers will then wait and see how rates of TB disease differs between the two groups over time.
"Our primary end point is to have 35 cases (across sites) of TB disease to be able to determine whether MTBVAC is protective. Candidates must also be HIV negative and not pregnant to qualify," says IAVI Medical Director, Dr Elana van Brakel.
She explains that were they to include people without exposure to TB, it would require tens of thousands of participants and take an immeasurably long time to conclude the trial. As it is, the trial is expected to take two to three years.
A live-attenuated vaccine
MTBVAC is a live-attenuated vaccine derived from the TB bug. In short, that means the vaccine contains a live, but much weakened version of the TB bacterium. The idea is that it is too weak to make you sick, but similar enough to normal TB bugs to allow your immune system to learn how to combat it. The vaccine is injected as a single dose between the layers of the skin.
"I'm delighted and proud about the progress made by Be Part and that the MTBVAC study is finally underway," says Professor Keertan Dheda of the University of Cape Town and Principal Investigator of the study.
He explains that developing an effective TB vaccine, unlike COVID-19, has been very difficult for a bunch of reasons, including lack of knowing exactly why some people are protected against TB and lack of reliable animal testing models.
"We also have no idea if one to two TB antigens or a whole bunch of them - as in a live vaccine like MTBVAC - is required for protection. So, we need to test as many approaches as possible. We can't wait another 10 years to find out if a specific vaccine has failed - we need to test a bunch in tandem," says Dheda.
"If successful, MTBVAC will not only save lives and have a major positive impact of South Africa's Gross Domestic Product, but it will also prevent severe disabling lung disease that affects millions who have been previously had TB," he adds.
The researchers are hoping that the MTBVAC vaccine will offer at least 50% protection for both adults and children. Apart from IMAGINE, there are several other trials of MTBVAC, among others testing its efficacy in neonates. MTBVAC is a phase 2b trial, while the trial in neonates is a phase 3 trial. Medicines and vaccines are typically only registered for use after safety and efficacy have been confirmed in large phase 3 trials.
The other headline-making TB vaccine candidate, M72, achieved efficacy of around 50% in phase 2 trials. That vaccine requires two jabs given a month apart, as opposed to the single shot with MTBVAC. As previously reported by Spotlight, a massive phase 3 trial of the M72 vaccine kicked off last year. (For a roundup of all the key TB vaccines in development, see this publication by Treatment Action Group, a New York-based advocacy think tank.)
The 'true heroes'
Back in Paarl, Hellström describes herself as "a big ideas person who can't do the rhetorical stuff". She says she cut her teeth in the impossibly busy Livingstone Tertiary Hospital in Port Elizabeth (now known as Gqeberha) and wrote a proposal for the Be Part clinic in Mbekweni in 2005.
At first, she says, they rented the land and erected basic buildings, but with savings from several studies they bought the land and developed the centre into the multi-faceted facility it is today, complete with a fire-proof data storage room, clinic space, doctor's offices, change rooms, ablution, a communal dining or socialising area and some high-end technical support equipment. The centre, which sits in the middle of the bustling township, has a staff complement of 42, ranging from community recruiters to student doctors, a paediatrician, four research nurses, study coordinators, and data technicians.
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During a tour of the facility, white-coated staff are seen bent over various tasks, and the atmosphere is one of jovial, engaged collegiality, with several local residents seated at tables being prepped for screening.
Van Brakel and Hellström describe the trial participants as the true heroes.
"They want to see change and [yet] get little out of what is after all, a trial, although it has every chance of success. They're going to potentially benefit their children or their children's children. They're not just coming because they were persuaded. They're proud to participate and feel like they're doing something that has the potential to change the world. It's a really committed partnership," Hellström enthuses.
The two doctors are in agreement on HIV and TB co-morbidity.
"They don't die of HIV - they die of TB...Their immune systems are broken down by HIV, but the TB is the final straw that the body can't fight anymore," says Van Brakel.
Disclosure: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation but is editorially independent - an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
