Mycobacterium bovis BCG-vaccination in the guinea pig model of tuberculosis (TB) is sufficiently protective that candidate TB vaccines are judged against this. Little is understood about how the BCG vaccine works and, in the absence of a definitive correlate of protection, it is difficult to interpret the significance of novel vaccine induced host responses. Here an extended custom-made microarray (86 guinea pig genes) was used to dissect temporal changes in BCG-vaccine induced gene signatures to different mycobacterial antigens. Initially at 4. h, pro-inflammatory genes such as IL-1α, IL-1β, IL-8 and GRO were up-regulated (P<0.001) and these were then superseded by IFN-γ and GM-CSF (at 12 and 20. h) post-stimulation, ex vivo with PPD. Similar genes were seen following stimulation with viable BCG but with the addition of IL-23 (P<0.01) after 8. h. Our results suggest that temporal changes in the up- and down-regulation of a variety of genes are required to trigger a successful protective response to TB in guinea pigs. This provides base-line information against which new TB vaccines can be compared.
Bibliographical noteFunding Information:
We are very grateful to Mr. Simon Clark and the Biological Investigations Group at the HPA for conducting the animal procedures. We also thank the Statistics Unit at Reading University for advice on analysing real-time PCR data. This work was funded by the Department of Health, UK and the views in this paper are those of the authors and not the funding body.
Copyright 2011 Elsevier B.V., All rights reserved.
- Guinea pig