HVTN 602 data repo: Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis

Data supporting submitted manuscript:
Title: Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis

One sentence summary: 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.

Authors: One B. Dintwe1,2,†, Lamar Ballweber Fleming1,†, Valentin Voillet1,2,†, John McNevin1, Aaron Seese1, Anneta Naidoo2, Saleha Omarjee2, Linda-Gail Bekker3, James G. Kublin1, Stephen C. De Rosa1,4, Evan W. Newell1, Andrew Fiore-Gartland1,‡, Erica Andersen-Nissen1,2,*,‡, and M. Juliana McElrath1,5,*,‡

Affiliations:
1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America
2Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town, South Africa
3The Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
4University of Washington School of Medicine, Department of Laboratory Medicine and Pathology, Seattle, Washington, United States of America
5University fo Washington School of Medicine, Department of Medicine, Seattle, Washington, United States of America
*Corresponding authors:
E-mail: [e-mail] (EAN) and [e-mail] (MJM)
†These authors contributed equally to this work.
‡These authors contributed equally to this work.

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.