An estimated 1.45 million people worldwide died of tuberculosis (TB) in 2018; in comparison, 770 000 died of HIV/AIDS. In South Africa, approximately 520 out of every 100 000 people contract TB every year—put another way, 301 000 South Africans developed TB in 20181. Some 64 000 South Africans died of TB disease that year. TB continues to cause misery as the leading global cause of death from infectious disease.
But South African researchers are fighting back: two research groups at the University of Cape Town (UCT) were part of an internationally-funded multi-country study of a new TB vaccine. And the results are promising.
On Tuesday 29th October, the prestigious medical journal the New England Journal of Medicine published the final results of a phase IIb study of a new TB vaccine. The vaccine, currently known by the code M72/AS01E, reduced the rate of TB lung disease in adults by half.
The researchers asked people who already had signs of carrying the TB bacterium (but who were not ill and did not have HIV) to join the trial.
The TB bacterium Mycobacterium tuberculosis can enter the human body and then persist without making the person ill, possibly for decades, until something triggers its activity. Researchers and doctors call this “latent TB”.
In contrast, “active TB” is the form which is more familiar: people with active TB of the lungs may have a persistent cough, fever, night sweats and unintended weight loss. TB is also able to infect almost any other body system, including the heart or the brain.
The World Health Organization estimates that nearly one-quarter of the global population has latent TB and could progress to active TB1. Currently, standard treatment for active TB involves a combination of four medicines, taken for six months. But the treatment can have unpleasant side-effects, and more and more TB infections are resistant to these drugs. There is currently no TB vaccine available that consistently protects adults (children receive some protection from the Bacillus Calmette–Guérin [BCG] TB vaccine they receive as babies, but it has various shortcomings and protection wears off by adulthood).
We will not be able treat our way out of the South African TB epidemic; an effective vaccine is first prize in the fight against TB.
The Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) and the South African Tuberculosis Vaccine Initiative (SATVI) at UCT are part of that fight. Their clinical research sites in Khayelitsha and Worcester in the Western Cape are two of 11 sites in South Africa, Kenya and Zambia where the study of M72/AS01E was conducted.
‘’We are pleased to have had a part in the conduct and analysis of this study. The results continue to be highly encouraging”, said Professor Robert J Wilkinson (CIDRI-Africa Director).
The researchers took the study to where there is the greatest need for a TB vaccine. People living in Khayelitsha are at extremely high risk of contracting TB. Here, the CIDRI-Africa team partners with local government and non-governmental organisations, including the Site B Community Health Centre, Médicins sans Frontières, Grassroot Soccer, and the TB/HIV Care Association, to reach people at risk of TB, learn about their experience of the disease, and offer them a place in studies. One hundred and sixty-three people joined the M72/AS01E study at the CIDRI-Africa site.
In total, 3 575 adults enrolled in the study across all 11 sites. Study participants were given two doses of either M72/AS01E or a placebo sugar solution injection 30 days apart and were monitored for three years to see whether they developed active TB of the lungs, and whether they experienced any side effects.
Thirteen of the 1626 participants who received the M72/AS01E injections developed active lung TB compared with 26 participants of the 1663 in the inactive group. That’s a reduction of 50%. The results are very encouraging.
Side effects were minimal and of the sort usually encountered with vaccination (injection site swelling and flu-like symptoms).
The researchers are keen to continue close laboratory examination of the samples that the study participants have provided to improve and build on this first positive result. The vaccine will also need to be rigorously tested in more clinical trials and only then could it be rolled out to the public. But this is the first signal of a potentially effective TB vaccine in almost 100 years. Certainly cause for optimism.
More about the study
The study was sponsored by the global healthcare company GSK, and conducted in partnership with IAVI, a non-profit organization dedicated to developing vaccines against HIV and TB.
This study is “phase IIb” of a potential three phases of testing. The study was placebo-controlled, randomized, and double-blind. This means that the active vaccine was compared with an inactive placebo injection so that the difference in effect could be accurately estimated; people who volunteered to participate were randomly assigned by computer to receive either the active vaccine or the placebo; and neither the study participants nor the staff at the clinic knew which injection they were receiving or administering.
The study protocol was approved by ethics committees and state regulatory bodies in every country in which it was conducted. A Safety Review Team and an Independent Data Monitoring Committee reviewed safety data while the trial was ongoing; if they had identified any serious danger to participants—attributable to the trial—the trial would have been stopped.
Everyone who joined the study participated in an informed consent process, which ensured that they understood the trial concept and that they subsequently freely agreed to join the trial. Study participants were also free to stop participating at any time.
The M72/AS01E vaccine contains a fusion protein derived from two Mycobacterium tuberculosis antigens (immune stimulating substances), and the AS01 adjuvant system (an adjuvant enhances the immune response to the immune stimulating substances in the vaccine).
The Wellcome Centre for Infectious Diseases Research in Africa fosters investigator-led approaches via the overarching scientific objective of combatting infection, especially HIV-1 and tuberculosis, through clinical and laboratory research. Three interlinked platforms support clinical studies in the community, improve the depth of laboratory investigations for infected materials, and advance cutting-edge integration of high-dimensional, big data.
The South African Tuberculosis Vaccine Initiative is a research group based at the University of Cape Town and with a field site in the town of Worcester, Western Cape, that focuses on understanding risk for and protection against tuberculosis, in order to develop a new safe and effective TB vaccine.
Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, Bollaerts A, Demoitié M-A, Diacon A, Evans TG, Gillard P, Hellström E, Innes JC, Lempicki M, Malahleha M, Martinson N, Mesia Vela D, Muyoyeta M, Nduba V, Pascal TG, Tameris M, Thienemann F, Wilkinson RJ, Roman F. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis. New England Journal of Medicine. 2019. DOI: 10.1056/NEJMoa1909953
Watch the press conference at which the results were announced