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J Infect Dis. 2015 May 1;211(9):1499-509. doi: 10.1093/infdis/jiu615. Epub 2014 Nov 7.

Gene expression and cytokine profile correlate with mycobacterial growth in a human BCG challenge model.

Author information

1
The Jenner Institute, University of Oxford, United Kingdom.

Abstract

BACKGROUND:

Bacillus Calmette-Guerin (BCG) vaccine is the most widely administered vaccine in the world, yet its mechanism of action remains unclear. We hypothesize that certain immune pathways are associated with reduced mycobacterial growth following BCG challenge in human volunteers.

METHODS:

We used samples from a mycobacterial challenge in which previously BCG-vaccinated or BCG-naive adults in the United Kingdom were challenged intradermally with a standard dose of BCG. Any remaining BCG was quantified in a skin biopsy specimen obtained 2 weeks after challenge and used as a measure of BCG growth and functional antimycobacterial immunity. We measured the immune response over the 2-week challenge, using DNA microarrays and flow cytometry, and correlated this with mycobacterial growth.

RESULTS:

The magnitude of the immune response to BCG is greater in previously vaccinated volunteers, and this correlates with reduced mycobacterial growth but increased scarring at the vaccination site. In particular, the interferon γ and interleukin 17 pathways are strongly induced in previously vaccinated volunteers and correlate with reduced mycobacterial growth in this population.

CONCLUSION:

This study identifies pathways associated with control of mycobacterial growth in vivo in human volunteers and supports the use of BCG challenge as a tool for evaluating vaccine efficacy and identifying mechanisms of antimycobacterial immunity.

KEYWORDS:

BCG; cytokines; transcriptomics; tuberculosis; vaccines

PMID:
25381367
PMCID:
PMC4392868
DOI:
10.1093/infdis/jiu615
[Indexed for MEDLINE]
Free PMC Article

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