frica is increasingly at the center of global clinical research, not only as a site for trials but as a critical partner in advancing new interventions for infectious diseases. This is particularly important for tuberculosis (TB), which continues to place a disproportionate burden on many African communities, driving high morbidity and mortality, especially among adolescents, adults, and people living with HIV.
Global Forum spoke with Devika Zachariah and Dakshina Reddy of the Gates Medical Research Institute (Gates MRI) about these efforts, which aim to overcome long-standing challenges in TB prevention and treatment.
Would you explain the background, purpose, and progress to date of the M72/AS01E TB vaccine trial across Africa?
The Gates Medical Research Institute (Gates MRI) is sponsoring the phase 3 clinical trial of the M72/AS01E tuberculosis vaccine, a vaccine candidate originally developed by GSK and licensed to Gates MRI for late-stage development. The trial is designed to evaluate whether M72/AS01E can prevent pulmonary TB in adolescents and adults, particularly those with latent TB infection, a population that accounts for a large share of TB transmission globally.
This phase 3 study is among the largest infectious disease vaccine trials ever conducted, enrolling approximately 20,000 participants across 54 trial sites in five countries (South Africa, Kenya, Zambia, Malawi, and Indonesia). It includes cohorts of IGRA positive, IGRA negative, and people living with HIV.
As of April 2025, the trial reached full enrollment roughly 11 months ahead of schedule, a major operational milestone. The study remains ongoing, with primary completion anticipated later in the decade and potential product availability around 2029, if efficacy and safety are confirmed.
What operational or regulatory inflection points made it possible to reach full enrollment nearly a year early, and what does that signal about the maturity of African trial ecosystems?
Multiple factors contributed to early full enrollment, which demonstrates the readiness and scale of the African trial infrastructure including experienced investigators, established high-incidence catchment areas, and strong collaboration with national regulatory authorities.
The trial leveraged existing high-performing research centers with prior TB and HIV trial experience, reducing potential site start-up delays. In addition, community advisory boards (CABs) and long-standing engagement structures supported rapid recruitment without compromising ethical standards.
Reaching full enrollment early signals a maturing African clinical research ecosystem capable of supporting complex, late-stage trials at a global scale.
A robust and mature clinical trial infrastructure in Indonesia also contributed to reaching the full enrollment milestone early.
Market-shaping efforts play an important role prior to wide-scale rollout of a new medicine. At what stage in product development does Gates MRI now integrate access planning?
Making vaccines accessible and affordable for communities in areas of high disease burden is a priority for all trial partners. The M72 partners Gates MRI, GSK, Wellcome, and the Gates Foundation are actively working alongside regulators and governments to understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term sustainable access, if and when it is approved. This includes supporting research and building an evidence base for the potential impact of the vaccine and community requirements for uptake, as well as collaborating with multilateral, regional, and country partners required to introduce the vaccine.
Are there similar initiatives underway in Africa that you’d also like to explain/describe?
Beyond vaccines, Gates MRI is engaged in TB drug development in Africa. Gates MRI is currently conducting phase 2 trials of novel, oral TB treatment regimens in drug-susceptible TB in South Africa. The ultimate aim of Gates MRI’s TB drug program is to develop a shorter, simpler TB treatment regimen to treat both drug-susceptible and drug-resistant TB.
Additionally, Gates MRI is conducting a phase 1 trial of a novel monoclonal antibody to prevent malaria. After a first-in-human clinical trial in adults was conducted in the United States, the current trial is being conducted in adults and children in Uganda.
Gates MRI is running early-phase and late-stage trials in TB and malaria simultaneously in multiple African countries. How do you avoid overconcentrating demand on high-performing sites while still accelerating development timelines?
Gates MRI uses a networked, strategic approach to site selection and trial management, not limited to only a few research institutes.
- Where appropriate, trials are distributed across many sites and countries, like the phase 3 M72 TB vaccine trial, which is being conducted at 54 sites across Kenya, Indonesia, Malawi, South Africa, and Zambia. This spreads out workload and speeds up timelines.
- Gates MRI leverages proven African trial research centers with their affiliated sites while also expanding into new areas, focusing on high-incidence communities experienced in relevant trials to maintain data quality and reduce overreliance on certain centers.
- The institute invests in the selection process and qualifying sites before large trials, as seen in the M72 program’s preparatory studies that identified sites with the highest incidence of TB to ensure that more sites could participate.
- Early and late-stage trials are run in parallel but often at different sites: Experienced centers handle advanced studies, while newer sites take on early-phase work, keeping operations efficient.
- Long-term partnerships and community engagement support recruitment, maintaining enrollment rates without overburdening specific populations or institutions.
From a sponsor’s perspective, where are the biggest remaining friction points in multicountry African trials today: Contracting, import/export logistics, pharmacovigilance systems, digital interoperability, or something else?
From Gates MRI’s perspective, the biggest remaining challenge points are not scientific or site capability related, but rather system-level operational and regulatory challenges which are many and varied across numerous countries.
Challenges include import/export logistics where there are delays related to customs clearance, variable interpretation of regulations, and country-specific documentation requirements, all of which can introduce unpredictable start-up and resupply timelines, even when sites themselves are fully ready to operate.
Differences in pharmacovigilance requirements are another area of friction, particularly in late-stage trials enrolling large populations (divergent safety reporting formats and reporting timelines), while multiple interfaces between sponsors, sites, and national authorities create additional operational complexity.
While local systems are strengthening, harmonized pharmacovigilance workflows across countries remain limited, increasing the coordination burden for multicountry trials. Regulatory capacity has improved substantially in many African countries, but regulatory duplication across countries remains a major challenge. Even when dossiers are aligned, sponsors must often navigate separate national reviews with different timelines, requirements, and sequencing, which can slow regional trial activation.
The African Medicines Agency (AMA) has been established to strengthen clinical development in Africa by building regulatory capacity in national authorities and harmonizing standards, guidelines, and reliance-based pathways, enabling more consistent, efficient, coordinated multicountry approval of clinical trials and products.
What lessons learned from these trials will improve clinical research and care for patients in Africa?
These trials demonstrate that large-scale, high-quality research can be conducted in African settings, which simultaneously strengthens local health systems, surveillance, and laboratory capacity. They also normalize adult and adolescent vaccination and prevention paradigms, which historically received less investment than pediatric programs.
Looking ahead 5-10 years, what would signal that Africa has moved from being a potential trial location to a coequal innovation partner in global product development?
Indicators would include African investigators leading global trials, earlier inclusion of African regulators in development planning, and routine codevelopment, rather than downstream participation. The M72 program already reflects movement in this direction through African leadership at national and site levels.
AMA aims to build the infrastructure, expertise, and systems needed to operate as a fully autonomous continental regulator—on par with agencies like the EMA and FDA—capable of independently overseeing and harmonizing medicines regulation across Africa.
There is growing emphasis on harmonization through regional bodies and strengthened national systems. Have you seen measurable reductions in review timelines, duplication, or unpredictability, and how does that compare to global benchmarks?
From Gates MRI’s perspective, the trend has been positive:
- Review timelines are shortening for harmonized pathways
- Duplication is decreasing where reliance is fully used
- Predictability is improving in a growing number of countries such as South Africa, Tanzania, and Zimbabwe among others where they have achieved WHO Maturity Level 3 regulatory systems with stable, well-functioning, integrated regulatory frameworks capable of supporting clinical development and reliance models.
However, although progress has been made, the system has not yet fully crossed the threshold where regional review outcomes reliably translate into rapid, synchronized national decisions across all participating countries.
Large-scale vaccine and prevention trials depend heavily on community trust. How is Gates MRI measuring meaningful engagement beyond enrollment numbers, particularly in settings with historical research inequities?
Gates MRI measures meaningful engagement not just by enrollment, but by sustained community advisory involvement, early and continuous engagement before recruitment, long‑term site-community partnerships, and evidence that community input actively shapes how trials are designed and conducted. For example, study sites host World TB Day events to provide touchpoints for participants and keep them updated and engaged.
Gates MRI-sponsored trials collaborate with CABs as part of clinical development programs. These bodies provide ongoing, structured input into trial design, consent processes, recruitment approaches, and issue escalation.
From Gates MRI’s standpoint, CABs are crucial partners in a trial’s success. CABs provide input that can lead to concrete protocol or operational adjustments.
For the phase 3 M72 TB vaccine trial, community engagement began during the preparatory epidemiologic study, well before participant recruitment for the vaccine trial. These preparatory activities were used to understand local disease burden, feasibility, and community concerns, and helped to build trust before pivotal clinical trials launched. This sequencing allows Gates MRI to view community readiness and build trust.
How can clinical research professionals interested in your work learn more about or perhaps even support/contribute to your work?
Clinical research professionals can engage through academic partnerships, trial site collaboration, and global health organizations involved in TB, HIV, and malaria research, including Gates MRI and its partners mentioned above.