Transcriptional and protein profiling reveal diverse subsets of effector memory CD4+ T-cell boosted by BCG revaccination that may be responsible for the partial protection conferred by this vaccination regimen.
Abstract
A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of South African adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis (M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we performed an in-depth characterization of cellular responses to BCG revaccination or to a H4:IC31 protein subunit 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 analysis with intracellular cytokine staining showed marked increases in five effector memory CD4+ T-cell subpopulations (TEM) after BCG revaccination, two of which were highly polyfunctional. CITE-Seq single cell analysis revealed that the activated subsets included an abundant cluster of Th1 cells with migratory potential. In addition, we identified a small cluster of Th17 TEM cells induced by BCG revaccination that expressed high levels of CD103, suggesting these cells may represent recirculating tissue-resident memory cells that could provide immune protection in the lung. Together, these results identify novel populations of CD4+ T cells for their potential as immune correlates of protection conferred by BCG revaccination.
R codes used to process the data (Seurat workflow) in the R folder.
.csv files to produce Figures are in the meta.data folder.