Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40957415.
- Also identified by DOI 10.1016/j.cell.2025.08.027 and PMC identifier 12445596.
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Abstract
Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, and Bacillus Calmette-Guérin (BCG) remains the only clinically approved vaccine. An enduring challenge in TB vaccine development is systematic antigen selection from a large repertoire of potential candidates. We performed an efficacy screen in mice of antigens that are targets of CD4 T cells in humans. We found striking heterogeneity in protective efficacy, and most of the top protective antigens are not currently in clinical development. We observed immunologic cross-reactivity among phylogenetically clustered antigens, reflecting common CD4 epitopes. We developed a trivalent mRNA vaccine consisting of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which augmented and exceeded BCG protection in multiple mouse models. Finally, we observed cellular immune responses to these antigens in 84% of humans exposed to M. tuberculosis. These data advance our understanding of TB vaccine immunology and define a vaccine concept for clinical development.
Medical subject headings
- Tuberculosis Vaccines
- Antigens, Bacterial
- Tuberculosis
- CD4-Positive T-Lymphocytes