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T-cell activation is an immune correlate of risk in BCG vaccinated infants

Author

Listed:
  • Helen A. Fletcher

    (Jenner Institute, University of Oxford
    London School of Hygiene and Tropical Medicine)

  • Margaret A. Snowden

    (Aeras)

  • Bernard Landry

    (Aeras)

  • Wasima Rida

    (Biostatistics Consultant)

  • Iman Satti

    (Jenner Institute, University of Oxford)

  • Stephanie A. Harris

    (Jenner Institute, University of Oxford)

  • Magali Matsumiya

    (Jenner Institute, University of Oxford)

  • Rachel Tanner

    (Jenner Institute, University of Oxford)

  • Matthew K. O’Shea

    (Jenner Institute, University of Oxford)

  • Veerabadran Dheenadhayalan

    (Aeras)

  • Leah Bogardus

    (Aeras)

  • Lisa Stockdale

    (Jenner Institute, University of Oxford
    London School of Hygiene and Tropical Medicine)

  • Leanne Marsay

    (Oxford Vaccine Group, University of Oxford)

  • Agnieszka Chomka

    (Kennedy Institute, Rheumatology and Musculoskeletal Sciences, University of Oxford)

  • Rachel Harrington-Kandt

    (Jenner Institute, University of Oxford)

  • Zita-Rose Manjaly-Thomas

    (Jenner Institute, University of Oxford)

  • Vivek Naranbhai

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Elena Stylianou

    (Jenner Institute, University of Oxford)

  • Fatoumatta Darboe

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Adam Penn-Nicholson

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Elisa Nemes

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Mark Hatherill

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Gregory Hussey

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Hassan Mahomed

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Michele Tameris

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • J Bruce McClain

    (Aeras)

  • Thomas G. Evans

    (Aeras)

  • Willem A. Hanekom

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Thomas J. Scriba

    (South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town)

  • Helen McShane

    (Jenner Institute, University of Oxford)

Abstract

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case–control analysis to identify immune correlates of TB disease risk in Bacille Calmette–Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR+ CD4+ T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25–2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR+ CD4+ T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068–1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29–0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

Suggested Citation

  • Helen A. Fletcher & Margaret A. Snowden & Bernard Landry & Wasima Rida & Iman Satti & Stephanie A. Harris & Magali Matsumiya & Rachel Tanner & Matthew K. O’Shea & Veerabadran Dheenadhayalan & Leah Bog, 2016. "T-cell activation is an immune correlate of risk in BCG vaccinated infants," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11290
    DOI: 10.1038/ncomms11290
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    Cited by:

    1. Iman Satti & Rachel E. Wittenberg & Shuailin Li & Stephanie A. Harris & Rachel Tanner & Deniz Cizmeci & Ashley Jacobs & Nicola Williams & Humphrey Mulenga & Helen A. Fletcher & Thomas J. Scriba & Mich, 2022. "Inflammation and immune activation are associated with risk of Mycobacterium tuberculosis infection in BCG-vaccinated infants," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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