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

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 Bogardus, Lisa Stockdale, Leanne Marsay, Agnieszka Chomka, Rachel Harrington-Kandt, Zita-Rose Manjaly-Thomas, Vivek Naranbhai, Elena Stylianou, Fatoumatta Darboe, Adam Penn-Nicholson, Elisa Nemes, Mark Hatherill, Gregory Hussey, Hassan Mahomed, Michele Tameris, J Bruce McClain, Thomas G. Evans, Willem A. Hanekom, Thomas J. Scriba and Helen McShane ()
Additional contact information
Helen A. Fletcher: Jenner Institute, University of Oxford
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
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

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11290

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