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Dintwe, One B.; Ballweber Fleming, Lamar; Voillet, Valentin; McNevin, John; Seese, Aaron; Naidoo, Anneta; Omarjee, Saleha; Bekker, Linda-Gail; Kublin, James G.; De Rosa, Stephen C.; Newell, Evan W.; Fiore-Gartland, Andrew; Andersen-Nissen, Erica; McElrath, M. Juliana
Nature communications, 06/2024, Volume: 15, Issue: 1Journal Article
Abstract A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis ( M.tb ). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4 + T cell subpopulations (T EM ) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 T EM cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4 + T cells with potential to be immune correlates of protection conferred by BCG revaccination.
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