MTBVAC, A NOVEL VACCINE AGAINST TUBERCULOSIS
Tuberculosis (TB) is a global public health problem caused by the bacillus Mycobacterium tuberculosis. This communicable disease is a major cause of ill health and one of the leading causes of death worldwide.
- Globally, an estimated 10.6 million people fell ill with TB in 2021, an increase of 4.5% from 2020 (10.1 million).
- There were an estimated 1.4 million TB deaths among HIV-negative people in 2021 and an additional 187,000 deaths among HIV-positive people.
- Until the COVID-19 pandemic, TB was the leading cause of death from a single infectious agent, ranking above HIV (WHO global TB report 2022)
BCG vaccine for tuberculosis overview
The main health care intervention available to reduce the risk of TB infection progressing to active disease is prevention. Currently, the only licensed vaccine against TB is the Bacille Calmette-Guérin (BCG).
BCG is a live attenuated strain of Mycobacterium bovis effective in reducing the rate of severe forms of TB occurring in infants and children, mainly in developing countries. However, this vaccine is inconsistent in preventing spread of pulmonary TB, the most common form of the disease in adolescents and adults.
There is a need for a new, improved and safe vaccine that is effective against all forms of TB disease in infants, children, and adults, and is safe in immune-compromised persons, including those with HIV infection.
MTBVAC: a novel tuberculosis vaccine
MTBVAC vaccine is a live-attenuated strain of M. tuberculosis designed by the research group of Dr. Carlos Martín Montañés from the Department of Microbiology at the University of Zaragoza, Spain, and Brigitte Gicquel from the Institut Pasteur, Paris. This vaccine is designed to provide improved efficacy compared to BCG, the current vaccine used against tuberculosis.
- To date, MTBVAC is the only live-attenuated M. tuberculosis vaccine evaluated in clinical trials that has demonstrated safety, efficacy and immunogenicity in both preclinical and clinical studies, making it one of the most promising TB vaccines worldwide.
- Unlike BCG, which lacks over 100 genes compared to the human pathogen, MTBVAC contains the full set of antigenic targets of the original pathogen.
- Through genetic engineering, a uniquely attenuated M. tuberculosis strain was generated, which has a similar antigen repertoire to virulent M. tuberculosis and contains known human T cell epitopes present in M. tuberculosis but absent in BCG.
- MTBVAC is designed to stimulate specific immune responses that mimic natural tuberculosis infection without causing disease.
Tuberculosis vaccine for newborns
Tuberculosis vaccine for adolescents and adults
Trials with MTBVAC
MTBVAC’s attenuation, toxicity, safety, and protection were first tested in mice and guinea pigs, at the University of Zaragoza, Spain.
The safety profile of MTBVAC has been evaluated in two completed early-phase clinical trials:
- The first was a human phase 1a conducted in Switzerland in 2014 (NCT02013245) to test MTBVAC’s safety and reactogenicity in healthy adults.
- The second was a phase 1b, double blind, controlled, randomized, dose-escalation, safety, and immunogenicity trial conducted in South Africa in 2017 (NCT02729571) to test MTBVAC in newborns with a safety arm of 9 adults.
Two additional clinical trials have been completed, and their results are being analyzed:
- A phase 1b/2a, randomized, double-blind, active-controlled, safety, immunogenicity, and dose-escalation trial tested MTBVAC in adults with and without latent TB in South Africa (NCT02933281).
- A phase 2a, dose-defining, safety, and immunogenicity trial of MTBVAC in newborn babies in South Africa (NCT03536117).
All the completed studies and preliminary results from the last two clinical trials indicate that MTBVAC is safe and well-tolerated.
Current MTBVAC trials
A phase 3 trial (NCT04975178) is underway to evaluate the efficacy, safety and immunogenicity of MTBVAC compared to BCG in healthy, HIV-unexposed and HIV-exposed uninfected newborns in tuberculosis-endemic regions of sub-Saharan Africa. This randomized, double-blind controlled trial aims to enroll 7120 newborns who have not received BCG vaccination and have not been exposed to Mycobacterium tuberculosis.
The trial will be conducted at six sites, including four in South Africa, one in Madagascar and one in Senegal.
Additional studies planned
- A phase 2a in HIV positive adolescents and adults that will start on the second half of 2023, in South Africa.
- A phase 1/2 in adolescents and adults, planned for the second half of 2023, in India.
- A phase 2b/3 in adolescents and adults planned for 2025 in different regions of the world.
Economic and Health Impact
of a new TB vaccine
Although the implementation of a TB vaccine would be highly cost-effective, investment will be needed to develop these vaccines. It is estimated that at least 1.25 billion US dollars will be needed per year to meet the objectives for TB vaccine development outlined in the Global Plan to End TB 2023-2030. However, compared to the annual cost of managing TB, or to the overall cost of TB for the global economy, investments in new TB vaccine candidates are only a fraction, with the potential to significantly reduce future costs.