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

Author

Listed:
  • One B. Dintwe

    (Fred Hutchinson Cancer Center
    Hutchinson Centre Research Institute of South Africa)

  • Lamar Ballweber Fleming

    (Fred Hutchinson Cancer Center)

  • Valentin Voillet

    (Fred Hutchinson Cancer Center
    Hutchinson Centre Research Institute of South Africa)

  • 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
    University of Washington School of Medicine)

  • Evan W. Newell

    (Fred Hutchinson Cancer Center)

  • Andrew Fiore-Gartland

    (Fred Hutchinson Cancer Center)

  • Erica Andersen-Nissen

    (Fred Hutchinson Cancer Center
    Hutchinson Centre Research Institute of South Africa)

  • M. Juliana McElrath

    (Fred Hutchinson Cancer Center
    University of Washington School of Medicine)

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.

Suggested Citation

  • 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 & Andr, 2024. "Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49050-1
    DOI: 10.1038/s41467-024-49050-1
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    1. Patricia A. Darrah & Joseph J. Zeppa & Pauline Maiello & Joshua A. Hackney & Marc H. Wadsworth & Travis K. Hughes & Supriya Pokkali & Phillip A. Swanson & Nicole L. Grant & Mark A. Rodgers & Megha Kam, 2020. "Prevention of tuberculosis in macaques after intravenous BCG immunization," Nature, Nature, vol. 577(7788), pages 95-102, January.
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