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


Matsumiya, M; Satti, I; Chomka, A; Harris, SA; Stockdale, L; Meyer, J; Fletcher, HA; McShane, H; (2014) Gene expression and cytokine profile correlate with mycobacterial growth in a human BCG challenge model. The Journal of infectious diseases. ISSN 0022-1899 DOI: 10.1093/infdis/jiu615

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Abstract

 Bacille Calmette Guerin (BCG) 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 a BCG challenge in human volunteers.  We used samples from a mycobacterial challenge in which previously BCG-vaccinated or BCG-naïve UK adults were challenged intradermally with a standard dose of BCG vaccine. Any remaining BCG was quantified from a skin biopsy two weeks post-challenge and used as a measure of BCG growth and functional anti-mycobacterial immunity. We measured the immune response over the two week challenge using DNA microarrays and flow cytometry, and correlated this with mycobacterial growth.  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 IFNγ and IL-17 pathways are strongly induced in previously vaccinated volunteers and correlate with reduced mycobacterial growth in this population.  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 anti-mycobacterial immunity.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 25381367
Web of Science ID: 354722000019
URI: http://researchonline.lshtm.ac.uk/id/eprint/2025477

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