As a young South African woman, I am deeply honoured to contribute to this foreword for the July TB Think Tank newsletter, particularly as Youth Month has just wrapped up. This month holds a profound significance for me, not just as a time to celebrate the vibrant spirit and potential of young people, but also as a crucial opportunity to reflect on the ongoing challenges we face, particularly in the fight against tuberculosis. 

My involvement in the TB space has been multifaceted. I’ve supported country and global teams in evaluating market shaping interventions and performed financial and economic analysis of key health systems investments related to TB. Over the years as an Associate at CHAI, I’ve been involved in various initiatives and programs aimed at improving treatment, care, and access to healthcare. My most significant contribution to the TB Access Program was my role in the introduction and implementation of the 3HP regimen. I also played a critical role in TB treatment forecasting. Working in the TB Access Program at the Clinton Health Access Initiative and supporting the Department of Health, I have gained valuable experience in the development and implementation of TB programs and new policies and guidelines aimed at improving the quality of TB care in our country. 

When I think about what is most needed to better support young people in TB research, care, or advocacy, a glaring gap comes to mind: accessible and relatable education. We need to move beyond traditional awareness campaigns and embrace innovative approaches that resonate with young audiences. This is where the power of social media becomes undeniable. Imagine TikTok challenges that demystify TB symptoms, Instagram stories featuring young survivors sharing their journeys, or YouTube explainers breaking down complex information into digestible, engaging content. We need to speak the language of our youth, leveraging platforms they already inhabit to relay messages on TB, how it affects all of us – even if we are not infected – and the importance of early diagnosis and adherence to treatment. Education needs to be culturally sensitive and tailored to diverse communities across our nation, ensuring that everyone understands the risks, symptoms, and the crucial message that TB is curable. 

Furthermore, we need to foster an environment where young people feel empowered to contribute to TB solutions. This means creating more opportunities for youth involvement in research, policy development, and community-level interventions. We need to listen to their perspectives, as they often bring fresh insights and innovative ideas to the table. By investing in young talent and providing mentorship, we can cultivate the next generation of TB champions. 

As we work towards a TB-free generation, I offer both a message of encouragement and a challenge to my fellow Think Tank members. Let us be relentless in our pursuit of innovation, not just in medical advancements, but also in how we communicate and engage with our communities, particularly our youth. Let us push the boundaries of traditional approaches and embrace the digital age to reach every corner of our nation. And let us never forget the human stories behind the statistics – the lives lost, the families affected, and the hope that each of us carries for a healthier future. Together, we can turn the tide against TB and build a legacy of health and well-being for generations to come. 

Omphile Ramokhoase 

For over a century, the Bacille Calmette-Guérin (BCG) vaccine has been the only licensed TB vaccine, offering protection primarily against severe forms of TB in young children, but with limited impact on TB disease in adolescents and adults. Today, hopes are high for the M72/AS01E-4 vaccine candidate, which could become the first-ever TB vaccine shown to prevent pulmonary TB in older age groups. 

This large-scale trial seeks to confirm the M72 vaccine’s ability to prevent active TB disease and to evaluate its safety and immune response in adolescents and adults, including people living with HIV (PLHIV). The results could mark a turning point in TB prevention efforts. We spoke with Prof Fairlie to better understand the trial’s design, its potential impact, and why this moment is so significant for TB prevention and care worldwide. 

Q: Can you provide a brief overview of the M72 vaccine trial, including its aims and what makes it significant in the TB vaccine landscape? 

A: The study is intended to evaluate M72/AS01E-4 compared to placebo in preventing TB disease progression. A total of 20,000 participants are enrolled from South Africa, Malawi, Kenya, Zambia and Indonesia. This includes 18,000 who tested positive by Interferon Gamma Release Assay (IGRA), 1000 who are IGRA-negative, and 1000 PLHIV. Around 60% of participants are from South Africa. In the previously completed Phase 2b trial, the M72 vaccine conferred approximately 50% protection at 36 months against developing laboratory-confirmed pulmonary TB disease when given to IGRA-positive, HIV-negative adults. This trial is designed to confirm the previously observed efficacy in IGRA-positive, HIV-negative people, as well as to generate safety and immunogenicity data in IGRA-positive and negative adolescents and adults, including PLHIV. 

Q: We understand that enrolment has now closed in South Africa. Can you share what this milestone means for the trial overall and what the next steps are? 

A: The study was enrolled 12 months ahead of schedule, which is a testament to the fantastic work done by South African and other country teams to enrol so quickly into this study. The exciting component is that this takes us a step closer to getting results from the study earlier, and hopefully TB vaccines into arms, if the study is successful. The next steps include continued follow-up of participants, strong retention, and ensuring the study continues to be conducted with the highest quality and rigour. The study end point will be reached once 110 participants are diagnosed with TB, so it is important that each diagnosis is well-characterised and accurately captured within the study.  

Q: The pace of enrolment at South African sites was impressive. What do you think contributed to this, and were there any lessons learned that could inform future TB vaccine uptake in the region? 

A: A number of factors likely contributed to faster-than-anticipated enrolment:  

Gates Medical Research Institute (MRI) worked closely with trial sites to select TB hotspots for enrolment. These areas are often densely populated communities facing socioeconomic challenges, where many people have family members or friends who became ill with TB. People understand that TB is a serious disease and that treatment is long and complicated. 

The trial sites have a history of engaging with the communities where they work and have built trust within these communities. Most sites have established community advisory boards (CABs), and Gates MRI has sought input from CABs that informed the vaccine development program and trial design. 

For future vaccines, most important factors are engaging with communities, ensuring they have a solid understanding of the disease, promoting research literacy, and addressing any myths and concerns about vaccines, providing ongoing education.  

Q: What are the key timelines going forward, particularly regarding follow-up, data collection, and the anticipated date for primary results? 

A: As mentioned, the study endpoint is met when there are 110 people diagnosed with TB. The team is closely watching the incidence rate within the study. Follow-up could be as short as three years, or as long as six years, depending on the incidence rate.  

Q: How are South African partners contributing to the implementation and scientific leadership of the trial, and how is this being recognised in the broader consortium? 

A: South African investigators have played key roles in the scientific development of the protocol, including protocol leadership, and currently hold positions on both the Trial Steering Committee (including the Chair) and the Scientific Advisory Committee. There is also an Implementation Science Consortium led by Professor Limakatso Lebina.  

Q: How are trial teams engaging communities and managing expectations, especially with growing excitement around the potential of M72?  

A: The study results are expected to take some time. The site teams are reassuring communities and participants that transparent communication and updates will occur as soon as any important information is available to be shared. Unfortunately, it is a long game! 

Q: Are there any messages you would like to share with the broader TB Think Tank audience about the future of TB prevention and where M72 fits in? 

A: If M72 is successful, it will be a gamechanger for TB prevention, especially in communities of highest need. Reducing or eliminating the need for TB preventive treatment, often in capacity-constrained environments where adherence is challenging, would be revolutionary. The impact could extend beyond health, potentially benefiting individuals who are protected from TB disease, and contributing to broader socio-economic gains for communities and society as a whole. 

In the global effort to end tuberculosis (TB), Africa is at the forefront of innovation—thanks in large part to the work of Prof Angelique Kany Kany Luabeya, Associate Professor and Principal Investigator at the South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town. 

Prof Luabeya is leading several promising TB vaccine trials. At the forefront is her role in the M72/AS01E Phase 3 trial, where she serves as principal investigator at SATVI’s site. This Gates Foundation–funded study follows encouraging Phase 2b results, which showed 49.7% efficacy, positioning M72 as the most promising TB vaccine candidate in decades. 

She also leads Phase 3 trials for the VPM1002 vaccine, a recombinant version of BCG that is being evaluated for safety and efficacy. In addition, Prof Luabeya is spearheading Africa’s first adult safety trials for MTBVAC, a live-attenuated TB vaccine, marking an important milestone in the continent’s vaccine development efforts. 

Her research into BCG revaccination has added valuable insight into the potential of boosting immune responses in adolescents. Although the Phase 2b trial demonstrated strong induction of Th1-cytokine-positive CD4 T cells, the study showed neutral efficacy against sustained infection. She also leads first-in-human trials of novel vaccine candidates, including H56:IC31, which is designed for both preventive and therapeutic use, and ID93+GLA-SE, aimed at preventing TB recurrence. 

During the COVID-19 pandemic, she played a key role as co-investigator in the South African Phase 2b trial of the Novavax NVX-CoV2373 vaccine. The trial generated critical data on vaccine performance against emerging variants and was published in The New England Journal of Medicine. Her contribution to this research provided valuable guidance for pandemic response strategies in South Africa and beyond. 

In addition to vaccine development, Prof Luabeya is advancing TB diagnostics through innovative approaches. She is the principal investigator on a SATVI-led project evaluating the use of tongue swab PCR for TB detection. This non-sputum-based diagnostic method demonstrated 90% sensitivity and holds significant promise for use in low-resource settings where conventional methods are often limited. 

Prof Luabeya’s influence extends into global health governance and collaborative research. She serves as a technical expert on the World Health Organization’s TB Vaccine Advisory Committee and has been recognised as a WHO-TDR Clinical Research Fellow. Her collaborative efforts include partnerships with the Gates Foundation for M72 implementation, the Serum Institute of India on manufacturing initiatives, and the Max Planck Institute on immunological research. 

With more than 85 peer-reviewed publications in leading journals such as The New England Journal of Medicine and The Lancet Respiratory Medicine, she continues to share her findings at major global health conferences, including the Global Forum on TB Vaccines and the Union World Conference on Lung Health. 

Through her leadership, scientific excellence and commitment to health equity, Prof Angelique Luabeya is helping shape the future of TB prevention in Africa and globally. Her work is a testament to the power of African-led research in delivering innovative, high-impact solutions to longstanding public health challenges. 

Important updates include a treatment decision algorithm to support diagnosis at lower levels of healthcare, the inclusion of additional specimens such as stool, for bacteriological testing, and guidance on treatment shortening for non-severe TB.  Another important change is the addition of ethambutol as a fourth drug in the treatment of non-severe TB in young children. This change helps streamline regimens and is especially important in the context of South Africa’s high HIV and drug-resistant TB burden. However, with only 400mg tablets currently available, accurate dosing for small children requires tablets to be crushed and diluted—a process that carries risk if not done correctly.  To facilitate this change, there is an urgent need for clear, easy-to-use tools for healthcare workers, pharmacists, and caregivers. 

To support the successful roll-out of these new guidelines, the Child, Adolescent and Maternal TB Task Team, with funding support from The Gates Foundation, partnered with consultants to develop practical materials for healthcare workers and caregivers. A user-friendly quick reference guide to help healthcare providers manage diagnosis, treatment and prevention of both drug-susceptible and rifampicin-resistant TB in children with confidence has been developed and is nearly ready for dissemination. The guide summarizes multiple guidelines into one easy to navigate reference booklet, following the course of a typical patient consultation. Other resources developed includes family friendly posters for clinics on screening, diagnosis and treatment administration as well as fact sheets for caregivers, with special attention being given to dosing tools and instructions for ethambutol to ensure young children get the right amount safely.  

By empowering healthcare workers and caregivers with clear, practical information, this initiative aims to reduce the TB treatment coverage gap and give every child with TB a better chance at a successful outcome. 

Important updates include a treatment decision algorithm to support diagnosis at lower levels of healthcare, the inclusion of additional specimens such as stool, for bacteriological testing, and guidance on treatment shortening for non-severe TB.  Another important change is the addition of ethambutol as a fourth drug in the treatment of non-severe TB in young children. This change helps streamline regimens and is especially important in the context of South Africa’s high HIV and drug-resistant TB burden. However, with only 400mg tablets currently available, accurate dosing for small children requires tablets to be crushed and diluted—a process that carries risk if not done correctly.  To facilitate this change, there is an urgent need for clear, easy-to-use tools for healthcare workers, pharmacists, and caregivers. 

To support the successful roll-out of these new guidelines, the Child, Adolescent and Maternal TB Task Team, with funding support from The Gates Foundation, partnered with consultants to develop practical materials for healthcare workers and caregivers.   A user-friendly quick reference guide to help healthcare providers manage diagnosis, treatment and prevention of both drug-susceptible and rifampicin-resistant TB in children with confidence has been developed and is nearly ready for dissemination.  The guide summarizes multiple guidelines into one easy to navigate reference booklet, following the course of a typical patient consultation.  Other resources developed includes family friendly posters for clinics on screening, diagnosis and treatment administration as well as fact sheets for caregivers, with special attention being given to dosing tools and instructions for ethambutol to ensure young children get the right amount safely.  

By empowering healthcare workers and caregivers with clear, practical information, this initiative aims to reduce the TB treatment coverage gap and give every child with TB a better chance at a successful outcome.