Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis

One B. Dintwe, Lamar Ballweber Fleming, Valentin Voillet, John McNevin, Aaron Seese, Anneta Naidoo, Saleha Omarjee, Linda-Gail Bekker, James G. Kublin, Stephen C. Rosa, Evan W. Newell, Andrew Fiore-Gartland, Erica Andersen-Nissen () and M. Juliana McElrath ()
Additional contact information
One B. Dintwe: Fred Hutchinson Cancer Center
Lamar Ballweber Fleming: Fred Hutchinson Cancer Center
Valentin Voillet: Fred Hutchinson Cancer Center
John McNevin: Fred Hutchinson Cancer Center
Aaron Seese: Fred Hutchinson Cancer Center
Anneta Naidoo: Hutchinson Centre Research Institute of South Africa
Saleha Omarjee: Hutchinson Centre Research Institute of South Africa
Linda-Gail Bekker: University of Cape Town
James G. Kublin: Fred Hutchinson Cancer Center
Stephen C. Rosa: Fred Hutchinson Cancer Center
Evan W. Newell: Fred Hutchinson Cancer Center
Andrew Fiore-Gartland: Fred Hutchinson Cancer Center
Erica Andersen-Nissen: Fred Hutchinson Cancer Center
M. Juliana McElrath: Fred Hutchinson Cancer Center

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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 (TEM) 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 TEM 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.

Date: 2024
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DOI: 10.1038/s41467-024-49050-1

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