Abstract
BackgroundNovel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult.MethodsTo better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix® HumanRef-8 Expression BeadChip (Illumina) to measure expression of >16,000 genes.ResultsWe found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-γ, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated.ConclusionOur results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG.
Highlights
Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG)
We concluded that gene expression profiles obtained by stimulating PBMC with BCG were not sufficiently different from expression profiles obtained by stimulating cells with purified protein derivative of tuberculin (PPD) to enable the samples to fall into separate clusters
We found that many genes up-regulated by both BCG and PPD in our infants' PBMC have previously been associated with adult Mφ1 macrophages, including IL-1β, IL-8, interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), interferon-inducible protein 10 (IP10), macrophage inflammatory protein (MIP)-1β and macrophage derived chemokine (MDC) (Table 2) [4,21,24-26]
Summary
Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. World-wide, two million people die from tuberculosis (TB) every year, and an estimated two billion people, a third of the world's population, are latently infected with Mycobacterium tuberculosis (M.tb). Bacille Calmette-Guérin (BCG), first used as a human vaccine in 1921, is one of the most widely administered vaccines in the world. Most novel vaccine candidates are designed to boost immunity that was primed by prior BCG vaccination; not enough is known about immunity induced by BCG in adults.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
