Journal Article

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

O’Shea, Matthew K., Naranbhai, Vivek, Chomka, Agnieszka, Mahomed, Hassan, Nemes, Elisa, Rida, Wasima, Matsumiya, Magali, Landry, Bernard, Satti, Iman, Harrington-Kandt, Rachel, Hanekom, Willem A., Evans, Thomas G., Marsay, Leanne, Darboe, Fatoumatta, Dheenadhayalan, Veerabadran, Stockdale, Lisa, Manjaly-Thomas, Zita-Rose, Harris, Stephanie A., Fletcher, Helen A., Bogardus, Leah, Scriba, Thomas J., Hussey, Gregory, Tanner, Rachel, Penn-Nicholson, Adam, Stylianou, Elena, Tameris, Michele, Hatherill, Mark, McClain, J Bruce, Snowden, Margaret A., McShane, Helen

2016

Overview

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. BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR + CD4 + T cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/106 / 13/21 / 13/31 / 631/250/2152/1566/1618 / 631/250/24/590 / 631/250/255/1856 / 692/700/1720 / Adolescent / Antibody Formation - immunology / Antigens / BCG Vaccine - immunology / Case-Control Studies / CD4-Positive T-Lymphocytes - immunology / Cohort Studies / Cytokines / Health risks / HLA-DR Antigens - immunology / Humanities and Social Sciences / Humans / Immunity / Immunization / Immunoglobulin G - immunology / Infant / Infants / Infections / Infectious diseases / Logistic Models / Lymphocyte Activation - immunology / Lymphocytes / Medicine / multidisciplinary / Mycobacterium tuberculosis - immunology / Pediatrics / Placebos / Regression analysis / Risk Factors / Science / Science (multidisciplinary) / Time Factors / Tuberculosis / Tuberculosis - blood / Tuberculosis - immunology / Tuberculosis Vaccines - immunology / Vaccination / Vaccines / Vaccines, DNA / Variables