MTBVAC-AVANTE

The challenge

Tuberculosis remains one of the world's leading infectious killers, causing more than one million deaths every year and disproportionately affecting low- and middle-income countries. 

More than 100 years have passed since the only TB vaccine, Bacille Calmette-Guérin (BCG), was first administered. Although BCG provides important but incomplete protection against severe disease in infants and young children, it has several important limitations: critically, it does not prevent progression to TB disease in adolescents and adults with Mycobacterium tuberculosis (Mtb) infections, among whom most transmission and disease occurs.

A new effective TB vaccine could have an enormous public health impact. While TB vaccine development is highly complex, years of scientific ingenuity and perseverance have brought multiple promising candidates into late-stage efficacy trials today. At the same time, efforts are advancing to lay the groundwork to ensure their introduction as rapidly as possible, should they be found safe and effective. This includes a range of country- and region-led approaches and work under the WHO TB Vaccine Accelerator Council.

One of the most advanced candidates is MTBVAC. MTBVAC is the only live, attenuated vaccine candidate derived from Mtb currently in development by Biofabri and uses a weakened, harmless form of the pathogen to stimulate an immune response. Genes that trigger disease have been removed from the Mtb genome, while retaining the full range of antigenic targets that are missing from BCG, which may be involved in generating an immune response against TB. Importantly, MTBVAC is being studied to prevent TB disease in both young children (as a superior alternative to BCG) and adolescents and adults (for whom no vaccine is yet licensed). 

Several MTBVAC clinical trials are underway. These include a Biofabri-sponsored phase 3 trial in infants (MTBVACN3, partly funded by EDCTP), which is recruiting more than 7,000 newborns in Madagascar, Senegal and South Africa, and an IAVI-sponsored phase 2b trial in adolescents and adults (IMAGINE), which is recruiting more than 5,000 participants at 16 clinical research centres in South Africa, Kenya, and Tanzania. A phase 2a trial sponsored by Fred Hutchinson (HVTN group) is meanwhile underway in adolescents and adults living with and without HIV in South Africa, while a phase 2 trial sponsored by Bharat Biotech has been completed among adolescents and adults in India. A Phase 3 trial is set to begin by the end of 2026 in adolescents and adults in India, also sponsored by Bharat Biotech. 

The project

Over the next four years, the MTBVAC-AVANTE, a 12-partner project, will work to advance the clinical development of MTBVAC and ensure that the clinical evidence produced is well placed to be translated into policy. Under the name Advancing a Vaccine for Adolescent/Adult and Neonatal TB Epidemic (MTBVAC-AVANTE), the project will support the expansion and completion of these two trials, as well as several concurrent and post-trial activities that will lay the ground for more rapid country introductions of MTBVAC, should it be found safe and effective.

• MTBVACN3: It will help ensure the successful conclusion of the trial and production of the final clinical summary report, as well as biobanking of samples from participants for future analysis. The project team plans to submit a licensing application to a regulatory authority, likely the European Medicines Agency (EMA), for the use of MTBVAC to prevent TB disease in neonates, followed by an extension to older age groups as more data become available.
• IMAGINE: The project will co-fund the expansion of the Phase 2b trial with the inclusion of an additional cohort to assess the safety and immunogenicity of participants who test negative on the IGRA test for Mtb infection. Under an earlier grant from Coefficient Giving, the IGRA negative cohort began enrolment in February 2026. The addition of around 1,200 Mtb-unexposed participants will complement the IMAGINE trial’s initial target of enrolling 4,300 participants with prior Mtb exposure (IGRA-positive) but without TB disease.
• Innovative exploratory objectives: The project funding will co-support the collection of sputum samples at three consortium partners (Ifakara Health Institute, Kenya Medical Research Institute, and University of Cape Town Lung Institute PTY LTD) to facilitate the future assessment of the contribution of different immune responses to protection against TB disease to inform future TB vaccine development. Samples will be stored in a biorepository overseen by IAVI and made available to experts for MTBVAC-correlates research, with biobanking supported by other grants.
• MTBVAC-AVENTE will also support regulatory and policymaker engagement. The project consortium will carry out a wide range of activities with national regulatory authorities and policymakers, as well as global stakeholders and regional procurement bodies. These engagements will lay the groundwork for timely licensing and policy translation to facilitate the introduction of MTBVAC and equitable access to it, should positive findings emerge from trials.

Impact

The MTBVAC-AVANTE project will help accelerate tuberculosis vaccine development and access by:

• Ensuring that key phase 2b and 3 trials of the MTBVAC vaccine candidate can be successfully completed in full.
• Facilitating sample collection, storage and analysis, generating evidence to support TB vaccine development.
• Enabling extensive engagement with regulatory authorities and policymakers to anticipate potential barriers and accelerate assessments by regulators and policymakers in high-burden countries.

The project will help move MTBVAC through clinical evaluation towards licensure and lay the groundwork for the timely introduction of a vaccine that could potentially save many thousands of lives a year, particularly in low-resourced settings where TB is most prevalent.