South Africa Lays Groundwork for Historic Adult TB Vaccine as Phase 3 Clinical Trials Advance

JOHANNESBURG — In a proactive move to tackle one of the world’s deadliest infectious diseases, the South African Department of Health announced it is actively preparing for the potential registration and national rollout of an experimental adult tuberculosis (TB) vaccine. The candidate, known as M72/AS01E, is currently undergoing pivotal Phase 3 clinical testing across seven countries. If trial results prove positive, M72/AS01E could become the first new TB vaccine introduced in more than 100 years, offering a long-sought line of defense for adolescents and adults who bear the brunt of disease transmission.

Health officials emphasized that laying delivery logistics, regulatory pathways, and procurement frameworks early is essential to eliminate unnecessary delays once clinical and safety evaluations are completed.

A Century-Old Gap in Infectious Disease Prevention

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains a major public health burden in South Africa and globally, causing over one million deaths worldwide each year. For over a century, public health programs have relied on a single vaccine: the Bacille Calmette-Guérin (BCG) vaccine, developed in 1921.

While the BCG vaccine is routinely administered to newborns and effectively protects infants against severe forms of pediatric TB, its protective effect fades by adolescence. It offers minimal protection against pulmonary TB—the contagious, lung-affecting form of the disease that develops in adults and drives community transmission.

“A vaccine that prevents active pulmonary disease in adolescents and adults is the single most needed tool to break the chain of TB transmission,” explained Dr. Lee Fairlie, Director of Maternal and Child Health at Wits RHI in Johannesburg and national principal investigator for the trial in South Africa. “BCG protects our children, but M72/AS01E could finally protect the broader community.”

The Clinical Science: What Early Data Reveals

The M72/AS01E candidate, developed by GSK and now being advanced in Phase 3 by the nonprofit Bill & Melinda Gates Medical Research Institute (Gates MRI) with support from Wellcome and the Gates Foundation, represents a major scientific departure. It combines a recombinant fusion protein derived from two M. tuberculosis antigens with GSK’s proprietary AS01E adjuvant system to stimulate a targeted immune response.

Earlier Phase 2b clinical trials conducted in Kenya, South Africa, and Zambia yielded historic results, demonstrating approximately 50% protection against active pulmonary TB disease among HIV-negative adults who were already infected with latent TB.

┌─────────────────────────────────────────────────────────────────────────┐
│                      M72/AS01E Clinical Timeline                        │
├───────────────────┬─────────────────────────────────────────────────────┤
│ Phase 2b Trial    │ Demonstrated ~50% efficacy against active pulmonary │
│                   │ TB in adults with latent infection.                 │
├───────────────────┼─────────────────────────────────────────────────────┤
│ Phase 3 Trial     │ Enrolling up to 20,000 participants across 60 sites│
│                   │ in 7 countries (began March 2024).                  │
├───────────────────┼─────────────────────────────────────────────────────┤
│ Regulatory Target │ Potential licensing and deployment targeted for     │
│                   │ ~2030 depending on final efficacy outcomes.         │
└───────────────────┴─────────────────────────────────────────────────────┘

While 50% efficacy is lower than that of some modern viral vaccines, mathematical modeling commissioned by the World Health Organization (WHO) shows that over a 25-year period, a TB vaccine with 50% efficacy could:

• Prevent up to 76 million new active TB cases globally.

• Avert 8.5 million deaths.

• Save millions of families from catastrophic healthcare expenditures.

The ongoing Phase 3 trial is enrolling up to 20,000 participants aged 15 to 44 across 60 clinical sites in South Africa, Kenya, Zambia, Malawi, Mozambique, Indonesia, and Vietnam. Crucially, the trial includes dedicated cohorts to evaluate safety and efficacy in people living with HIV, who face a significantly higher risk of developing active TB.

Policy, Logistics, and Prioritizing High-Risk Populations

South Africa’s decision to begin implementation planning years ahead of licensure aligns with expert recommendations published in PLOS Global Public Health. The study highlighted that while broad population vaccination across adolescents and adults remains the ultimate goal, initial supply limits will require prioritized distribution.

Key implementation strategies identified by health policy experts include:

• Phased Priority Rollout: Initial doses will likely target healthcare workers, individuals living with HIV, and household contacts of active TB patients.

• Service Integration: Combining TB vaccination drives with existing adult health platforms, such as antiretroviral therapy (ART) clinics and workplace wellness programs.

• Regulatory Alignment: Fast-tracking technical reviews with the South African Health Products Regulatory Authority (SAHPRA) as safety data accumulates.

“Preparing delivery systems and financing mechanisms in advance ensures that when a regulatory green light is given, vaccine doses reach clinic shelves without delay,” said Dr. Alemnew Dagnew, who leads clinical development of M72/AS01E at Gates MRI.

Manufacturing Scale and Regional Access

To address historical inequities where low- and middle-income countries faced delayed access to new medical breakthroughs, global health partners have established manufacturing agreements early.

The South African Department of Health confirmed it was briefed on global production plans involving the Serum Institute of India—the world’s largest vaccine manufacturer by volume—to supply bulk doses globally. Furthermore, the framework includes progressive technology transfers to support local manufacturing in South Africa and Indonesia. Localizing production strengthens regional health security while fostering economic growth and skilled pharmaceutical capacity within Africa.

Real-World Limitations and Immediate Guidance

Public health leaders urge the public to view these developments with measured optimism. The M72/AS01E candidate remains an investigational medical product, and final Phase 3 trial data must demonstrate clear efficacy, long-term durability, and safety across diverse populations before any authority grants approval.

Public health officials emphasize that current TB control practices must continue unabated:

1. Early Symptom Screening: Anyone experiencing a persistent cough lasting more than two weeks, fever, unexplained weight loss, or night sweats should seek immediate testing at a health facility.

2. Adherence to Treatment: TB remains curable with standard multi-drug antibiotic regimens, provided patients complete their full treatment course.

3. Preventive Therapy: High-risk individuals, including household contacts of TB patients and people living with HIV, should consult healthcare providers about preventive treatment.

If Phase 3 trials succeed, M72/AS01E will not replace existing diagnostic tools or antibiotic treatments; rather, it will serve as a cornerstone in a comprehensive strategy to finally end tuberculosis as a public health threat.

References

1. https://www.eurasiareview.com/03082026-south-africa-prepares-for-potential-new-adult-tb-vaccine/

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.