Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines
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1-s2.0-S0092867425009821-main.pdf
Description
Published version
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3.97 MB
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Author(s)
Vidal, Samuel J
Lasrado, Ninaad
Tostanoski, Lisa H
Chaudhari, Jayeshbhai
Mbiwan, Esther R
Neka, Ganad D
Strutton, Ellis A
Espinosa Perez, Alejandro A
Sellers, Daniel
Barrett, Julia
Date Issued
September 15, 2025
Journal
Cell
Publisher
Elsevier BV
Citation
Vidal, Samuel J, Lasrado, Ninaad, Tostanoski, Lisa H, Chaudhari, Jayeshbhai, Mbiwan, Esther R et al. 2025. "Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines." Cell, 188.
Version
Final published version
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.cell.2025.08.027
