A Comparative Analysis of Polyfunctional T Cells and Secreted Cytokines Induced by Bacille Calmette-Guérin Immunisation in Children and Adults

Nicole Ritz,Nigel Curtis,Willem A Hanekom,Marc Tebruegge,Binita Dutta,Tom G Connell,Carmen Yau,Warwick J Britton,Madeleine Strach,Roy Robins-Browne

doi:10.1371/journal.pone.0037535

Abstract

BCG vaccine is one of the most commonly-administered vaccines worldwide. Studies suggest the protective efficacy of BCG against TB is better for children than for adults. One potential explanation is that BCG induces a better protective immune response in children. Twenty six children and adults were immunised with BCG. The proportion of Th1-cytokine-producing mycobacterial-specific T cells, and the concentrations of secreted cytokines, were measured before and 10 weeks after BCG immunisation. A significant increase in the proportion of mycobacterial-specific cytokine-producing T cells was observed in both age groups. After BCG immunisation, children and adults had comparable proportions of mycobacterial-specific polyfunctional CD4 T cells when measured relative to the total number of CD4 T cells. However, relative to the subset of Th-1-cytokine-producing CD4 T cells, the proportion of polyfunctional cells was greater in children. Concentrations of secreted cytokines were comparable in children and adults. These findings suggest that the mycobacterial-specific cell-mediated immune response induced by BCG immunisation in children and adults is similar. The implication of a shift to a more polyfunctional immune response within the Th1-cytokine-producing CD4 T cells in children is uncertain as this aspect of the immune response has not been assessed as a potential correlate of protection against TB.

Highlights

Bacille-Calmette-Guerin (BCG) is one of the most commonly administered vaccines worldwide with more than 100 million doses given each year
Investigating differences in the immune response between children and adults is important to understand the immunological mechanisms underlying protective efficacy against TB induced by BCG immunisation
This may provide an explanation for the difference in protective efficacy afforded by BCG immunisation in children and adults

Summary

Introduction

Bacille-Calmette-Guerin (BCG) is one of the most commonly administered vaccines worldwide with more than 100 million doses given each year. Neonatal BCG immunisation has been shown to induce antigen-specific interferon (IFN)-c-producing CD4 and CD8 T cells [6,7,8,9,10], proliferation of CD4 [11,12], CD8 [7] and c/d T cells [10,11], cytotoxicity in CD8 T cells [7,12], secretion of a variety of cytokines and chemokines [8,9,11,12,13,14,15], and more recently, the induction of mycobacterial-specific polyfunctional CD4 T cells [10,16]. Few studies have investigated the immune response to BCG in recently-immunised adults In this age group, BCG has been shown to induce a mycobacterial-specific IFN-c response. Differences in the immune response induced by BCG between children and adults might explain the difference in protective immunity conferred by BCG in these age groups

Materials and Methods

Results

Discussion