In South Africa, 26,000 people contract tuberculosis each year, representing 440 cases per 100,000 inhabitants. This figure places the country among the most affected worldwide by a disease that kills 1.3 million people annually. Yet the reference vaccine, BCG, dates from 1921 and only protects adults at 20%. One hundred and three years later, M72/AS01E becomes the first vaccine candidate to reach phase 3 clinical trials with 50% efficacy in adults.

The phase 3 trial, launched at the end of 2024, recruits 20,000 adult and adolescent participants in South Africa, Kenya, Zambia, and the Philippines. The stakes go beyond the scientific scope: this vaccine could transform the fight against a disease that affects 10.6 million people worldwide, 87% concentrated in Asia and Africa.

50% Efficacy That Doubles BCG’s Performance in Adults

Phase 2b results, published in Nature Medicine, show that M72/AS01E prevents 50% of active pulmonary tuberculosis cases in adults infected with the bacillus. This performance contrasts with BCG’s 20% efficacy in this population. The vaccine was tested on 3,573 participants in Kenya, South Africa, and Zambia between 2014 and 2018.

The difference is explained by biology. BCG effectively protects children against severe forms of tuberculosis, such as tuberculous meningitis. But its efficacy drops drastically after adolescence. M72/AS01E targets a specific protein of the tuberculosis bacillus, M72, coupled with an AS01E adjuvant that stimulates the immune response. This approach proves more adapted to the adult immune system.

Trial participants all had latent tuberculosis infection, meaning they harbored the bacillus without symptoms. This population represents 1.7 billion people worldwide according to the WHO. Among them, the risk of developing active tuberculosis reaches 5 to 15% over a lifetime. M72/AS01E halves this risk.

20,000 Participants to Validate Large-Scale Efficacy

The phase 3 trial, dubbed “ARGO TB,” constitutes the largest anti-tuberculosis vaccine study ever conducted. The 20,000 participants, aged 12 to 60, are distributed across four countries: 8,000 in South Africa, 5,000 in Kenya, 4,000 in Zambia, and 3,000 in the Philippines. All have latent tuberculosis infection confirmed by blood tests.

Half will receive M72/AS01E in two injections spaced two months apart, the other half a placebo. Follow-up will last three years to measure efficacy against active pulmonary tuberculosis. Evaluation criteria include bacteriological confirmation through sputum or cultures, as well as clinically diagnosed forms.

This phase 3 corrects a limitation of the previous trial: genetic homogeneity. Phase 2b mainly concerned populations of European ancestry in South Africa. The inclusion of Kenya, Zambia, and the Philippines diversifies genetic and epidemiological profiles. Tuberculosis strains vary by region, as do HIV co-infections.

The $550 million funding comes from Wellcome Trust (up to $150 million) and the Bill & Melinda Gates Foundation (approximately $400 million). GSK, which holds the vaccine license, contributes $100 million. The financial commitment reflects the stakes: no anti-tuberculosis vaccine has passed this stage since BCG’s creation.

Sub-Saharan Africa Concentrates 40% of Global Cases

The trial’s geographical distribution reflects that of global tuberculosis. Sub-Saharan Africa has 2.9 million cases, or 27% of the global total. Southeast Asia records 4.4 million, or 41%. These two regions concentrate 68% of cases for 35% of the global population.

South Africa displays the world’s highest incidence rate: 440 cases per 100,000 inhabitants in 2022. HIV multiplies the risk of active tuberculosis by 19, explaining this prevalence. 60% of South African tuberculosis patients are co-infected with HIV. This situation makes the country a representative testing ground for future challenges.

The Philippines represents a different dynamic. Incidence there reaches 650 cases per 100,000 inhabitants, but HIV co-infection remains marginal. Resistant strains are progressing: 25% of new cases show resistance to at least one first-line antibiotic. This growing resistance reinforces vaccination urgency.

Kenya and Zambia offer intermediate profiles. Kenyan incidence rises to 240 cases per 100,000 inhabitants, Zambia’s to 300. Both countries combine high HIV prevalence and emerging bacterial resistance. They illustrate tuberculosis progression in developing but functional health systems.

Logistical Challenges Reminiscent of COVID

The trial anticipates future deployment challenges. M72/AS01E requires two injections spaced two months apart, as emergency vaccination campaigns conducted since 2000 have shown. This logistical constraint raises questions in areas where healthcare access remains irregular.

The vaccine must be stored between 2 and 8°C, the standard temperature for vaccine cold chains. Unlike COVID mRNA vaccines, it doesn’t require freezing. This thermal stability facilitates distribution in tropical countries, where ambient temperature often exceeds 30°C.

The cost remains undisclosed. GSK commits to applying an “access price” in developing countries, without specifying the amount. The comparison with BCG, which costs $0.50 per dose, will serve as reference. The WHO estimates that an effective anti-tuberculosis vaccine could be cost-effective up to $50 per complete series in high-incidence countries.

Mass production represents another challenge. GSK has a capacity of 100 million annual doses for the AS01E adjuvant, used in its shingles vaccine. Scaling up will be necessary to cover the 1.7 billion people with latent infection. Industrialization could take five to seven years after regulatory authorization.

2030 as Commercialization Horizon

Phase 3 results are expected for 2027-2028. In case of success, the regulatory file will be submitted to American and European agencies during 2028. Authorization could occur in 2029, opening the way to commercialization in 2030.

This timeline aligns with WHO objectives of reducing tuberculosis incidence by 90% by 2035. An effective adult vaccine constitutes the missing tool in this strategy. Current preventive treatments, based on antibiotics taken for 3 to 6 months, show 60% adherence rates. A two-dose vaccine would drastically simplify prevention.

The economic impact could be considerable. Tuberculosis costs $21 billion annually in care and $40 billion in lost productivity. A 50% reduction in incidence would save $30 billion per year, or 600 times the investment in vaccine development.

Participating countries will benefit from priority access. This clause, negotiated during funding agreements, guarantees preferential deliveries during the first two years of commercialization. It reproduces the mechanism established for COVID vaccines with the COVAX initiative.

M72/AS01E opens a unique window of opportunity after a century of vaccine impasse. The 2027 results will determine whether this laboratory promise can transform one of humanity’s oldest epidemics.

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