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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.

Original publication

DOI

10.1038/ncomms11290

Type

Journal article

Journal

Nat Commun

Publication Date

12/04/2016

Volume

7

Keywords

Adolescent, Antibody Formation, BCG Vaccine, CD4-Positive T-Lymphocytes, Case-Control Studies, Cohort Studies, HLA-DR Antigens, Humans, Immunity, Immunoglobulin G, Infant, Logistic Models, Lymphocyte Activation, Mycobacterium tuberculosis, Placebos, Risk Factors, Time Factors, Tuberculosis, Tuberculosis Vaccines, Vaccination