DOI: 10.6084/m9.figshare.24150492
title: HVTN 602 data repo: Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis

description: Data supporting submitted manuscript:<b>Title: Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to </b><b><i>Mycobacterium tuberculosis</i></b><br><b>One sentence summary:</b> 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.<br><b>Authors:</b> One B. Dintwe<sup>1,2,</sup><sup>†</sup>, Lamar Ballweber Fleming<sup>1,</sup><sup>†</sup>, Valentin Voillet<sup>1,2,</sup><sup>†</sup>, John McNevin<sup>1</sup>, Aaron Seese<sup>1</sup>, Anneta Naidoo<sup>2</sup>, Saleha Omarjee<sup>2</sup>, Linda-Gail Bekker<sup>3</sup>, James G. Kublin<sup>1</sup>, Stephen C. De Rosa<sup>1,4</sup>, Evan W. Newell<sup>1</sup>, Andrew Fiore-Gartland<sup>1,</sup><sup>‡</sup>, Erica Andersen-Nissen<sup>1,2,*,</sup><sup>‡</sup>, and M. Juliana McElrath<sup>1,5,*,</sup><sup>‡</sup><br><b>Affiliations:</b><sup>1</sup>Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America<sup>2</sup>Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa<sup>3</sup>The Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa<sup>4</sup>University of Washington School of Medicine, Department of Laboratory Medicine and Pathology, Seattle, Washington, United States of America<sup>5</sup>University fo Washington School of Medicine, Department of Medicine, Seattle, Washington, United States of America*Corresponding authors:E-mail: eanderse@hcrisa.org.za (EAN) and jmcelrat@fredhutch.org (MJM)<sup>†</sup>These authors contributed equally to this work.<sup>‡</sup>These authors contributed equally to this work.<br><b>Abstract:</b>A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of South African adolescents reduced the risk of sustained infection with <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>). 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 (T<sub>EM</sub>) 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 T<sub>EM</sub> 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.