16 July 2026 — The Phase 2b IMAGINE clinical trial of the tuberculosis vaccine candidate MTBVAC has reached full enrollment of 5,500 participants across 16 centres in South Africa, Kenya, and Tanzania, IAVI and Biofabri/Zendal announced. The milestone represents a critical step in the global effort to develop a new TB vaccine to complement the Bacille Calmette-Guérin (BCG) vaccine, which has been in use for over a century and provides variable protection against pulmonary TB in adults and adolescents.
The IMAGINE Trial
The IMAGINE trial (formally designated NCT05947890 on ClinicalTrials.gov) is a Phase 2b study evaluating the safety and efficacy of MTBVAC in preventing active TB lung disease. First vaccinations were reported on 19 February 2025, at a site in Paarl, South Africa, and the trial reached full enrollment on 16 July 2026 — approximately 17 months after the first dose was administered.
The trial includes cohorts of both people with and without TB infection, allowing researchers to assess the vaccine's performance across different population groups. In July 2026, IAVI announced the enrollment of the cohort of people without TB infection, completing the trial's enrollment target.
Why a New TB Vaccine Matters
Tuberculosis remains the world's leading infectious disease killer, claiming approximately 1.25 million lives annually according to WHO estimates. The existing BCG vaccine, first administered in 1921, provides consistent protection against disseminated TB in children but offers variable and often limited protection against pulmonary TB in adults — the most common and transmissible form of the disease.
The need is especially acute in Africa, where TB is the leading cause of death among people living with HIV. The convergence of the HIV and TB epidemics in southern and eastern Africa has created a syndemic that existing tools have struggled to contain.
MTBVAC: A Live Attenuated Candidate
MTBVAC is a live attenuated vaccine derived from a clinical isolate of Mycobacterium tuberculosis, developed by researchers at the University of Zaragoza in Spain and manufactured by Biofabri (a subsidiary of the Zendal group). Unlike the BCG vaccine, which is derived from Mycobacterium bovis (a cattle-adapted strain), MTBVAC is based on the human pathogen itself — with specific virulence genes deleted to render it safe while preserving immunogenic properties.
This design rationale offers a potential advantage: by using the human TB bacillus as its backbone, MTBVAC may present a broader array of antigens to the immune system than BCG, potentially eliciting a more relevant and protective immune response against M. tuberculosis infection.
The Wider TB Vaccine Pipeline in 2026
MTBVAC is one of several TB vaccine candidates in clinical development during 2026, a year that has seen both progress and disappointment in the field.
PreVenTB Phase III Results (April 2026)
In April 2026, results from the Phase III PreVenTB trial — evaluating two candidates, VPM1002 and Immuvac — were published. The study found that while both vaccines were safe, they did not meet the primary endpoint of significantly preventing microbiologically confirmed TB disease. The results were a setback for the field, demonstrating the difficulty of improving upon BCG's partial protection.
M72/AS01E: The Ongoing Hope
The M72/AS01E candidate, which showed 54% efficacy in a landmark Phase 2b trial across Kenya, South Africa, and Zambia (results published in 2018 and subsequently reported by FIRAT), continues to be a primary focus for researchers. Hopes remain for a Phase III study launch in 2026, which would represent the most advanced TB vaccine trial in the pipeline.
| Candidate | Type | Stage (as of July 2026) | Key Feature |
|---|---|---|---|
| MTBVAC | Live attenuated M. tuberculosis | Phase 2b (IMAGINE) — fully enrolled | Based on human TB bacillus |
| M72/AS01E | Subunit + adjuvant | Phase 3 planned | 54% efficacy in Phase 2b |
| VPM1002 | Recombinant BCG | Phase 3 (PreVenTB) — failed primary endpoint | rBCG with urease deletion |
| Immuvac | Inactivated M. indicus pranii | Phase 3 (PreVenTB) — failed primary endpoint | Heat-killed, whole-cell |
The African Trial Network
The IMAGINE trial's placement across three African nations reflects the continent's central role in TB vaccine research. South Africa, which has one of the world's highest TB incidence rates, has been a critical site for TB vaccine trials for over two decades. The inclusion of Kenya and Tanzania broadens the geographic and epidemiological diversity of the study population.
What Comes Next
With full enrollment achieved, the IMAGINE trial will now follow participants to assess the incidence of active TB disease in the vaccinated group compared to the control group. Results are expected to inform decisions about advancing MTBVAC to a Phase 3 efficacy trial.
The TB vaccine field in 2026 is characterised by a paradox: the pipeline is richer than at any point in history, with multiple candidates in late-stage trials, yet no new vaccine has been licensed since BCG a century ago. The PreVenTB results demonstrated that success is not guaranteed, and the field awaits the IMAGINE trial results and the potential launch of the M72/AS01E Phase 3 study with cautious optimism.
Sources
- IAVI: Phase 2b clinical trial of promising TB vaccine candidate MTBVAC has reached full enrollment, July 2026.
- IAVI and Biofabri/Zendal press release: First vaccinations in the IMAGINE clinical trial, February 2025.
- ClinicalTrials.gov: NCT05947890 — Evaluating the Safety and Immunogenicity of MTBVAC.
- CIDRAP: First doses announced in Phase 2 trial for TB vaccine candidate.
- Treatment Action Group: PreVenTB Phase III trial results, April 2026.
- Gavi: TB vaccine research developments, 2026.
FIRAT Editorial Board
Institutional Research Desk · Foresight Institute of Research and Translation
The collective editorial and research translation board of FIRAT, synthesising peer-reviewed evidence, policy briefs, and division milestones across our seven foundational research pillars.
