T-cell activation is an immune correlate of risk in BCG vaccinated infants.
;
Margaret A Snowden;
Bernard Landry;
Wasima Rida ;
Iman Satti;
Stephanie A Harris;
Magali Matsumiya;
Rachel Tanner;
Matthew K O'Shea;
Veerabadran Dheenadhayalan;
+20 more...
Leah Bogardus;
Lisa Stockdale;
Leanne Marsay;
Agnieszka Chomka;
Rachel Harrington-Kandt;
Zita-Rose Manjaly-Thomas;
Vivek Naranbhai;
Elena Stylianou;
Fatoumatta Darboe;
Adam Penn-Nicholson;
Elisa Nemes;
Mark Hatherill;
Gregory Hussey;
Hassan Mahomed;
Michele Tameris;
J Bruce McClain;
Thomas G Evans;
Willem A Hanekom;
Thomas J Scriba;
Helen McShane;
(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
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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