Two mRNA vaccines show promising efficacy against tuberculosis
Tuberculosis remains the world’s leading cause of death from a single infectious agent, with over one million deaths in 2024. Current treatments, which are long and often poorly tolerated, struggle to curb the spread of the disease, especially among adolescents and adults, where the existing BCG vaccine offers limited protection. In response, researchers have developed two experimental mRNA vaccines designed to target multiple proteins of the tuberculosis bacillus at different stages of infection.
These vaccines, tested on mice, have demonstrated their ability to trigger a strong immune response. They stimulate both antibody production and the activation of T cells, which are essential for fighting infection. The trials revealed a significant reduction in bacterial load in the lungs and spleens of animals infected with two different strains of the bacteria. Additionally, the vaccines promoted the infiltration of CD8+ T cells into granulomas, structures formed by the immune system to isolate bacteria. These cells, with a memory precursor phenotype, suggest long-lasting protection.
Tolerance tests in rats confirmed the absence of serious side effects. Observed inflammatory reactions, such as a temporary increase in white blood cells or acute-phase proteins, remained moderate and disappeared within a few weeks. These results indicate that the vaccines are well-tolerated and safe for potential use in humans.
The design of the vaccines is based on a multi-antigen approach, combining eight proteins from the bacillus. Each vaccine uses a slightly different mRNA technology, but both versions have shown similar performance in terms of immunogenicity and efficacy. The antibodies produced were also able to bind to the native proteins of the bacteria, confirming their biological relevance.
These advances pave the way for clinical trials already underway to assess the safety and efficacy of these vaccines in humans. If the results are confirmed, these vaccines could represent a major solution in the fight against tuberculosis, particularly in populations where BCG is insufficient.
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Original Publication
DOI: https://doi.org/10.1038/s41590-026-02545-z
Title: mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models
Journal: Nature Immunology
Publisher: Springer Science and Business Media LLC
Authors: Neha Agrawal; Louis S. Ates; Stefan A. Schille; Anuhar Chaturvedi; Janina Vogt; Natasa Vukovic; Charles L. Dulberger; Annette B. Vogel; Jan Diekmann; Mustafa Diken; Uğur Şahin