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Nat Commun. 2016 Apr 12;7:11290. doi: 10.1038/ncomms11290.

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

Author information

1
Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
2
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London W1CE7HT, UK.
3
Aeras, Rockville, Maryland 20850, USA.
4
Biostatistics Consultant, 1129 N. Illinois Street, Arlington, Virginia 22205, USA.
5
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford OX3 7LE, UK.
6
Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LF, UK.
7
Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX37BN, UK.
8
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child Health, University of Cape Town, Cape Town 7935, South Africa.

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.

PMID:
27068708
PMCID:
PMC4832066
DOI:
10.1038/ncomms11290
[Indexed for MEDLINE]
Free PMC Article

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