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


CONCLUSIONS
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.
The Jenner Institute, University of Oxford, United Kingdom.
Magali
M
Matsumiya
The Jenner Institute, University of Oxford, United Kingdom.
Iman
I
Satti
The Jenner Institute, University of Oxford, United Kingdom.
Agnieszka
A
Chomka
The Jenner Institute, University of Oxford, United Kingdom.
Stephanie A
SA
Harris
The Jenner Institute, University of Oxford, United Kingdom.
Lisa
L
Stockdale
The Jenner Institute, University of Oxford, United Kingdom.
Joel
J
Meyer
The Jenner Institute, University of Oxford, United Kingdom.
Helen A
HA
Fletcher
The Jenner Institute, University of Oxford, United Kingdom.
Helen
H
McShane
D017209:Apoptosis; D001500:BCG Vaccine / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D006019:Glycolysis; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009163:Mycobacterium bovis / Q000276:immunology*; D017192:Skin Diseases, Bacterial / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes
D001500:BCG Vaccine; D016207:Cytokines
BCG; cytokines; transcriptomics; tuberculosis; vaccines