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

Fletcher, HAORCID logo; Snowden, MA; Landry, B; Rida, WORCID logo; Satti, I; Harris, SA; Matsumiya, M; Tanner, R; O'Shea, MK; Dheenadhayalan, V; +20 more...Bogardus, L; Stockdale, L; Marsay, L; Chomka, A; Harrington-Kandt, R; Manjaly-Thomas, Z; Naranbhai, V; Stylianou, E; Darboe, F; Penn-Nicholson, A; Nemes, E; Hatherill, M; Hussey, G; Mahomed, H; Tameris, M; McClain, JB; Evans, TG; Hanekom, WA; Scriba, TJ; McShane, H and (2016) T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nature communications, 7 (1). 11290-. ISSN 2041-1723 DOI: 10.1038/ncomms11290
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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.


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