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

Article scientifique 2016 Anglais

Résumé

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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Fletcher, H., Snowden, M., Landry, B., Rida, W., Satti, I., Harris, S., Matsumiya, M., Tanner, R., O’Shea, M., Dheenadhayalan, V., 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, J., Evans, T., Hanekom, W., Scriba, T., McShane, H. (2016). T-cell activation is an immune correlate of risk in BCG vaccinated infants. https://doi.org/10.1038/ncomms11290

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Auteur(s)

Helen A. Fletcher Margaret Ann Snowden Bernard Landry Wasima Rida Iman Satti Stephanie A. Harris Magali Matsumiya Rachel Tanner Matthew K. O’Shea Veerabadran Dheenadhayalan 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 Michèle Tameris J. Bruce McClain Thomas G. Evans Willem A. Hanekom Thomas J. Scriba Helen McShane

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