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AbstractVaccines 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 ofMycobacterium 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

Nature Communications

Publisher

Springer Science and Business Media LLC

Publication Date

01/09/2016

Volume

7