T-cell Activation is an Immune Correlate of Risk in BCG Vaccinated Infants

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 13

PMID 27068708

Citations 151

Authors

Helen A Fletcher

Margaret A Snowden

Bernard Landry

Wasima Rida

Iman Satti

Stephanie A Harris

Magali Matsumiya

Rachel Tanner

Matthew K OShea

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

Affiliations

Soon will be listed here.

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.

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