Cell · 2025
Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines.
СтатьяНазвание и аннотация: Перевод в очереди
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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, Lifton Michelle, Wakabayashi Shoko, Eshaghi Behnaz, Borducchi Erica N, Aid Malika, Li Wenjun, Scriba Thomas J, Jaklenec Ana, Langer Robert, Barouch Dan H
Аннотация
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.