Year: 2016
Type: article
Abstract: 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.
Source: Nature Communications
DOI: 10.1038/ncomms11290
Authors: Helen A. Fletcher, Margaret A. 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, Michele Tameris, J Bruce McClain, Thomas G. Evans, Willem A. Hanekom, Thomas J. Scriba, Helen McShane
Institutions: University of Oxford, London School of Hygiene & Tropical Medicine, Jenner Institute, Aeras, Virginia Commonwealth University, Kennedy Institute of Rheumatology, Centre for Human Genetics, University of Cape Town, South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,974
OpenAlex ID: W2340217599