The world desperately needs an effective TB vaccine to reduce the illness and death still being caused by the centuries’ old bacterium, writes Chris Bateman in Spotlight, who 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 the experimental vaccine was administered on 19 February at the Paarl site. Called MTBVAC, the jab, 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 around 1.5m lives annually, more than 50 000 of them in South Africa.
To definitively turn the tide on TB, many experts concur that an effective vaccine is needed. The one TB vaccine available, Bacillus Calmette Guérin (BCG), is more than 100-years-old and offers only partial protection against TB in children.
In recent years, research funders have 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 Immunisation for a Neglected Epidemic. With a projected 4 300 participants, it will be the largest study so far of MTBVAC.
Spotlight 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, a valley between Paarl Mountain and the Drakenstein Mountains, was chosen because of the area’s very high TB rates. Multiple HIV and Covid-19 trials have previously been run at the site.
Dr Lize Hellström, principal investigator and founder of the 20-year-old centre, said the first vaccination of MTBVAC (or a saline placebo) was administered to their first triallist on 19 February 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,” said 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 unite 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 to ensure this,” said Esteban Rodriguez, CEO of Biofabri.
Testing in people with latent TB
Back at the Mbekweni site, Hellström said: “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 – who have the bug in their lungs, but who are not ill with the disease. Only around 10% of people with latent TB infection end up falling ill with TB disease.
In short, one group of participants is receiving the MTBVAC jab while another group gets a placebo. The researchers will then see how rates of TB disease differ 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,” said IAVI medical director Dr Elana van Brakel.
She said 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, meaning it 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 under way,” said Professor Keertan Dheda of the University of Cape Town and Principal Investigator of the study.
He said developing an effective TB vaccine, unlike Covid-19, has been very difficult for various reasons, including not 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,” said Dheda.
The researchers hope 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.
The ‘true heroes’
Back in Paarl, Hellström describes herself as “a big ideas person who can’t do the rhetorical stuff”. She said she cut her teeth in the impossibly busy Livingstone Tertiary Hospital in Gqeberha, and wrote a proposal for the Be Part clinic in Mbekweni in 2005.
At first, she said, 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, ablutions, a communal dining or socialising area and some high-end technical support equipment. The centre, in the middle of the bustling township, has 42 staff, ranging from community recruiters to student doctors, a paediatrician, four research nurses, study coordinators, and data technicians.
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 as if they’re doing something that has the potential to change the world. It’s a really committed partnership,” Hellström said.
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,” said Van Brakel.
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Landmark TB vaccine trial kicks off in SA
SA in multi-million dollar trial for new TB vaccine