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We can finally see hope on the horizon for beating TB, the world’s deadliest disease

We can finally see hope on the horizon for beating TB, the world’s deadliest disease
Willem Hanekom
By Willem Hanekom
23 Mar 2025
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As we mark World TB Day on 24 March, we stand on the threshold of creating only the second tuberculosis vaccine ever, and the first in more than a century since the BCG vaccine in 1921.

It is a fact that TB has long been the number-one infectious disease killer globally (other than when Covid-19 briefly took the mantle). According to the World Health Organization (WHO), more than 3,500 people die of TB every day.

This is a pandemic that especially burdens the socioeconomically dispossessed. The world’s highest incidence rate is in sub-Saharan Africa and in particular southern Africa, where hundreds of thousands become ill annually.

Allow me to be clear: vaccination is the only way we can bring TB completely under control.

So it is fitting that as we mark World TB Day on 24 March, we can proudly say that Africa, primarily South Africa, is playing an outsize role in the development of a TB vaccine that holds the greatest promise since the invention of the BCG vaccine more than 100 years ago.

This new vaccine candidate, called M72/AS01E, is currently in a phase 3 clinical trial — which evaluates whether the vaccine can prevent TB disease — in five countries: South Africa (SA), Zambia, Malawi, Kenya and Indonesia, with the most trial sites situated in SA.

The Gates MRI, a non-profit organisation and subsidiary of the Gates Foundation, is sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome. GSK is an active partner in the vaccine’s development, providing Gates MRI with technical guidance and supplying the adjuvant for phase 3 trials and roll out, should the trial be successful.

BCG, introduced in 1921, remains an effective vaccine for controlling TB — but only in infants. For us to bring TB to heel completely, we need a vaccine that works for the people who spread the disease most: adolescents and adults.

Allow me to be clear: vaccination is the only way we can bring TB completely under control. We have medications to treat TB and interventions to prevent people from contracting TB, but they are relatively difficult to deploy, especially compared with the simplicity of one or two vaccine shots. And they have limited effectiveness, as is commonly known.

M72 may be the vaccine we need


But in M72, we may have the vaccine we need. It has been shown to have an acceptable safety profile, and a phase 2b trial indicated that it is 50% effective against prevention of laboratory-confirmed pulmonary TB; a subsequent sensitivity analysis showed potential efficacy of 68%. These are incredibly promising results, which meet (and potentially far exceed) the WHO’s 50% efficacy requirement for a novel TB vaccine.

It must be noted that these early studies were not definitive. But the phase 3 trial currently underway would be definitive: it is a double-blind study involving 20,000 people (of whom more than 19,000 have already been enrolled). This trial, which meets the highest research standards, is also moving apace, and is anticipated to be completed in 2027 or 2028.

While the M72 trials show extraordinary promise, I must, however, note some significant challenges associated with developing and deploying the vaccine. These include working out how to incorporate adolescent and adult vaccinations into countries’ health systems which are geared towards administering the BCG to babies; vaccine hesitancy in target populations; and the requirements of some countries that vaccines be manufactured and tested in their jurisdictions.

In addition, demand for a vaccine for which phase 3 has not been completed is difficult to predict, and investment into vaccine manufacturing facilities ideally has to occur at-risk to avoid delays in scaling up supply.

This is also why it is critical to have contingency approaches to vaccine development; it makes little sense to bet everything on one approach only, and there are several other TB vaccine initiatives on the go.

One promising project is an mRNA vaccine being developed by the Universities of the Witwatersrand and Cape Town, based on findings from studying large cohorts of people from the Western Cape. This project proves that Africa — and South Africa — is taking its place at the forefront of scientific endeavour, as well as participating in trials.

Quite simply, the advantages of successfully developing and distributing a vaccine such as M72 are many, and manifest. The WHO lists several key benefits:

  • A significant reduction in TB incidence and deaths, as well as elimination of drug resistance to the disease;

  • Economic benefit, in the sense that the cost of immunisation would be offset by savings in the future costs in TB treatment and macroeconomic gains. Cost-effectiveness would particularly benefit countries with a high TB incidence, such as South Africa;

  • Improvement in health equity, by preventing TB in poorer, more vulnerable communities and promoting universal health coverage;

  • Achievement of several UN Sustainable Development Goals (SDGs), including eradicating poverty (SDG 1), eradicating hunger (SDG 2), promoting good health and well-being (SDG 3), and promoting decent work and growth (SDG 8); and

  • Greater investment in research and development, leading to quicker availability of TB vaccines, and from there, strong public health and economic impacts.


Admittedly, much work remains to be done, including jumping through several hoops — regulatory, policy, financial, procurement, implementation and supply — before the M72/AS01E vaccine can be administered to the public. The need is increasingly urgent, too, as reversal of some US funding to SA increases the risk that significant TB and HIV health gains of the past 20 years may be undone.

But as a clinician and immunologist who has dedicated decades of my career to the development of a TB vaccine, I believe we stand on the threshold of creating only the second such vaccine ever, and the first in more than a century.

I am excited and filled with hope that we will, at last, get a grip on this uncontrolled killer — and I am thrilled that we are part of the solution. DM

Professor Willem Hanekom is the executive director of the Africa Health Research Institute (AHRI), an independent, transdisciplinary scientific research institute. He is the co-national principal investigator for the M72/AS01E trial in South Africa. He directed the South African Tuberculosis Vaccine Initiative before leading the TB vaccine group at the Bill & Melinda Gates Foundation.

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