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Other publication, 2011

Global transcriptional response to ISCOM matrix at the site of administration and in draining lymph nodes after intramuscular injection in pigs

Ahlberg, Viktor; Lövgren, Bengtsson Karin; Wallgren, Per; Fossum, Caroline

Abstract

ISCOM vaccines are characterised by a balanced Th1/Th2 response and induction of CTLs. The adjuvant component, ISCOM-matrix, consists of purified saponins, cholesterol and phospholipids. However, the mode of action for the ISCOM-matrix is still largely unknown, especially concerning its modulation of gene expression in the innate immunity. To address this, the early global transcriptional response to ISCOM-matrix was studied in pigs. ISCOM-matrix, Matrix M (AbISCO® 100), was given as intramuscular injection and the Affymetrix GeneChip® Porcine Genome Array was applied to analyse gene expression at the injection site and in the draining lymph node after 24 hours. A total of 594 and 362 genes were differentially expressed (fold change > 2; q < 0.05) at the injection site and in the lymph node, respectively. At the injection site, the cytokines osteopontin (SPP1), IL-10 and IL-18 and the chemokines CCL2, CCL19 and CXCL16 were up-regulated. In the draining lymph node, IL-1β and CXCL11 were up-regulated but IL18, CCL15 and CXCL12 were down-regulated. AbISCO® 100 also modulated genes for several pattern recognition receptors at the injection site (TLR2, TLR4, MRC1, PTX3) and in the draining lymph node (TLR4, RIG-I, MDA5, OAS1, PRKR). Furthermore, a strong interferon induction was indicated; 54.3 % (n = 50) and 28.1 % (n = 108) of the up-regulated genes in the lymph node and at the injection site, respectively, were identified as interferon-regulated genes, of which several are known to be involved in host response to pathogens. In conclusion, ISCOM-matrix, without any antigen added, has a clear immunomodulatory effect at the site of administration as well as in the draining lymph node. These findings could help to reveal yet unknown mechanisms for how the ISCOM-matrix and ISCOMs mediate their adjuvant activity

Keywords

Adjuvant; innate immunity; gene expression; microarray; porcine

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