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

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-gamma 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.