Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling by array of liver from C57BL6 mice transfected with AAV8 vectors expressing either GFP or human macrophage inhibitory factor (MIF) or none (PBS).

ABSTRACT: MIF is a general mediator of inflammatory responses and is associated with several inflammatory diseases including atherosclerosis. Therefore MIF is currently investigated as a therapeutic target for atherosclerosis. Generation of AAV8 vectors expressing human MIF was initiated to overexpress human MIF in AAV8 target tissues (liver, heart, muscles) of C57/Bl6 to study biological function of MIF in vivo and to provide an animal model for testing of MIF antibodies. Aim of the gene expression profiling experiment: Livers of AAV8-CMV-MIF treated animals in order to identify established and potential novel target genes of MIF induced signalling

ORGANISM(S): Mus musculus

SUBMITTER: Eric Simon

PROVIDER: E-MTAB-1019 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Human papilloma (HPV) virus-like particle (VLP) vaccines were recently licensed. Though neutralizing antibody titers are thought to be the main effectors of protection against infection, early predictors of long-term efficacy are not yet defined and a comprehensive understanding of innate and adaptive immune responses to vaccination is still lacking. Here, microarrays were used to compare the gene expression signature in HPV-16 L1 VLP-stimulated PBMC from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization. Vaccination with HPV-16 L1 VLP was associated with modulation of genes involved in the inflammatory/defense response, cytokine, interferon and cell cycle pathways in VLP-stimulated PBMC. In addition, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and galectin (LGALS2). Twenty-two differentially expressed probesets were selected for confirmation by RT-PCR in an independent sample set. Agreement with the microarray data was seen for over two-thirds of these probesets. Up-regulation of immune/defense response genes by VLP, in particular interferon-induced genes was observed in PBMC collected prior to vaccination, with many of these genes being further induced following vaccination. In conclusion, we used gene expression profiling to identify important innate and adaptive response related- genes induced by vaccination with HPV VLP. Further studies are needed to identify gene expression signatures of immunogenicity and long-term protection with potential utility in prediction of long-term HPV vaccination outcomes in clinical trials. Experiment Overall Design: Microarrays (Affymetrix Human Focus) were used to compare the gene expression signature in PBMCs stimulated for 3 days with media alone, Sf9/baculovirus insect cell lysate, and HPV-16 L1 VLP expressed from baculovirus-infected Sf9 insect cells from 17 vaccine and 4 placebo recipients before vaccination, and 1 month after receiving the second immunization (2 months after the initial immunization. Post-vaccination baculovirus sample for Pt078 and pre-vaccination baculovirus sample for Pt082 failed QC.

Dataset Information

Transcription profiling by array of liver from C57BL6 mice transfected with AAV8 vectors expressing either GFP or human macrophage inhibitory factor (MIF) or none (PBS).

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