MTBVAC moves toward its final stage: the vaccine candidate that could mark a turning point in the fight against tuberculosis

On the occasion of World Tuberculosis Day, the latest data from the European Region show that this disease continues to be a major public health challenge. According to the joint report by the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC), 161,569 cases were reported in 2024 across 51 of the 53 countries in the European region, equivalent to 17.2 cases per 100,000 inhabitants. Despite progress made since 2015, the reduction in incidence and mortality remains below the set targets, jeopardizing the achievement of international goals for 2030.

One of the main challenges is the diagnosis gap: it is estimated that nearly one in five tuberculosis cases goes undetected in Europe. This means that thousands of people do not receive the necessary treatment and may continue transmitting the disease within their communities. In the European Union and the European Economic Area, although rates have stabilized, limitations in healthcare systems persist, hindering early diagnosis and proper patient follow-up.

Adding to this situation is the growing challenge of drug-resistant tuberculosis, whose prevalence in the European Region is well above the global average. In 2024, around 23% of new cases were multidrug-resistant, compared to 3.2% globally. These forms of the disease are more complex to treat, require longer treatment regimens, and have lower success rates, reinforcing the urgency to improve diagnostic, treatment, and control strategies.

The BCG vaccine (Bacillus Calmette-Guérin) has been used for more than a century to prevent tuberculosis. It is made from an attenuated strain of Mycobacterium bovis and is primarily administered in childhood. “BCG has been a fundamental tool in reducing severe forms of tuberculosis in children, but its protection against pulmonary tuberculosis in adolescents and adults is variable. In addition, the disease is closely linked to socioeconomic factors, access to diagnosis, and the emergence of resistant strains,” explains Rolando Pajón Feyt in an interview. He is an international expert in immunotherapy and vaccine development, Chief Medical and Scientific Officer of Biofabri, the human vaccines subsidiary of the biopharmaceutical group Zendal.

As he notes, the BCG vaccine has begun to lose effectiveness in some regions and “does not have a discernible impact in interrupting transmission or providing robust protection across all stages of life. That is why it is still necessary to develop more effective new vaccines.”

MTBVAC, the promising vaccine candidate that could change the fight against tuberculosis

In this context, MTBVAC, a tuberculosis vaccine candidate developed by Biofabri, is in an advanced stage of clinical development. “MTBVAC is based directly on Mycobacterium tuberculosis, the human pathogen, whereas BCG is derived from Mycobacterium bovis. This means that MTBVAC retains key antigens present in the original pathogen and absent in BCG.” Pajón notes that MTBVAC “more faithfully represents the pathogen that can attack us,” providing more precise training for the immune system. “This could generate a broader and potentially more protective response against infection and disease progression.”

Phase 2 trials have shown a favorable safety profile in both adults and newborns, comparable to that of BCG. In addition, superior immune responses have been observed against specific antigens of the human pathogen Mycobacterium tuberculosis. “These signals of increased immunogenicity, along with preclinical data, support the advancement toward large-scale efficacy studies,” Pajón explains, emphasizing that “MTBVAC is also the only live attenuated vaccine based on M. tuberculosis that has reached Phase 3 clinical development.”

The company began a Phase 3 trial in newborns in South Africa, Madagascar, and Senegal approximately one year ago, and it is still ongoing. “Phase 3 studies require several years, especially for diseases like tuberculosis, whose clinical progression is slow. Although we do not yet have final efficacy results, the study is progressing as planned with high standards of safety and clinical monitoring.”

Biofabri is also evaluating MTBVAC in people with and without HIV, a population particularly vulnerable to tuberculosis. “Having specific clinical evidence in this group is essential. It is not enough to show that a vaccine works in the general population. In tuberculosis, we also need to understand how it performs in especially vulnerable individuals. This study may provide key information on safety and immunogenicity in people with HIV.”

The interview concludes with a look toward a future in which MTBVAC demonstrates its efficacy and obtains regulatory approval. In that scenario, its availability could represent a significant advance in the fight against tuberculosis, especially in regions with the highest disease burden, helping to reduce incidence, mortality, and pressure on healthcare systems.

In addition, MTBVAC “has a global access program, with regional partners that would ensure its availability to all people who need it, at an appropriate price for the healthcare systems in those regions. This approach to accessibility from its conception makes this candidate very different. It is not a vaccine for 10 years from now, but a vaccine for the present, which is exactly what we need,” he adds.

“Our vaccine, when it arrives, will be one more tool within what should be integrated and synergistic strategies: better health, better quality of life, better therapeutic options, and more effective prevention. And it is precisely in prevention where we aim to help change the course of the fight against tuberculosis, the deadliest pathogen in the world in terms of annual mortality,” he concludes, noting that the WHO has stated that current progress remains insufficient to meet global targets, “which reinforces the urgent need for new preventive tools.”