title: Global transcriptional response to ISCOM-Matrix adjuvant at the site of administration and in the draining lymph node early after intramuscular injection in pigs.
abstract: ISCOM vaccines induce a balanced Th1/Th2 response, long-lasting antibody responses and cytotoxic T lymphocytes. The mode of action for the adjuvant component, the ISCOM-Matrix, is known to some extent but questions remain regarding its mechanism of action. The Affymetrix GeneChip® Porcine Genome Array was applied to study the global transcriptional response to ISCOM-Matrix in pigs at the injection site and in the draining lymph node 24h after i.m. injection. Gene enrichment analysis revealed inflammation, innate immunity and antigen processing to be central in the ISCOM-Matrix response. At the injection site, 594 genes were differentially expressed, including up-regulation of the cytokines osteopontin (SPP1), IL-10 and IL-18 and the chemokines CCL2, CCL19 and CXCL16. Of the 362 genes differentially expressed in the lymph node, IL-1β and CXCL11 were up-regulated whereas IL18, CCL15 and CXCL12 were down-regulated. ISCOM-Matrix also modulated genes for pattern recognition receptors at the injection site (TLR2, TLR4, MRC1, PTX3, LGALS3) and in the lymph node (TLR4, RIG-I, MDA5, OAS1, EIF2AK2, LGALS3). A high proportion of up-regulated interferon-regulated genes indicated an interferon response. Thus, several genes, genetic pathways and biological processes were identified that are likely to shape the early immune response elicited by ISCOM-based vaccines.
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. viktor.ahlberg@slu.se
authors.forename: Viktor
authors.initials: V
authors.lastname: Ahlberg
authors.forename: Karin
authors.initials: K
authors.lastname: Lövgren Bengtsson
authors.forename: Per
authors.initials: P
authors.lastname: Wallgren
authors.forename: Caroline
authors.initials: C
authors.lastname: Fossum
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D020869:Gene Expression Profiling; D016882:ISCOMs / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D034421:Sus scrofa / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016882:ISCOMs