Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1178182 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31129872.fastq.gz | Fastqsanger.gz | |||
| SRR31129873.fastq.gz | Fastqsanger.gz |
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Project description:M. rosenbergii exposes to VLP and WTD
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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.
2008-11-22 | E-GEOD-13587 | biostudies-arrayexpress
Project description:We engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity in vivo. VLPs encapsulating TLR7 agonists were decorated with a synthetic mannose-derived ligand (VLP-Man-OvaI/II) that selectively engages the lectin DC-SIGN. Lectin-TLR7 dual engagement induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand (VLP-PE-OvaI/II) failed to promote DC-mediated cellular responses. We performed bulk RNA-seq experiments on moDCs treated with VLP-Man-OvaI/II and VLP-PE-OvaI/II or unstimulated control moDCs. A total of 486 genes were differentially expressed after treatment with VLP-Man-OvaI/II vs. VLP-PE-OvaI/II (log2FC >1.5 and p<0.05). The significantly upregulated genes included CXCL1, CXCL5, ISG15, IL6, CCL4, ISG20, and SOCS3, all of which are implicated in the TLR7 downstream signaling pathway, suggesting a higher extent of TLR7 activation with the VLP-Man-OvaI/II. Gene set enrichment analysis (GSEA) between VLP-Man-OvaI/II- and VLP-PE-OvaI/II-treated moDCs revealed that hallmark DC activation pathways were also upregulated in VLP-Man-OvaI/II-treated DCs, including pathways related to IFN-a, IFN-g, and TNF-a signaling via nuclear factor-κB (NF-kB). These data give insight into how lectin binding with glycan-costumed VLPs can be employed to reprogram immunity.
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Project description:For development of gene expression of L5 spinal tissue in SNL mice, L5 spinal nerve was first tightly ligated to construct the neuropathic pain model, and sham-operated group as a control. After chronic administrations of vehicle (distilled water, 10 mg/kg) or WTD (12.60 g/kg, p.o.), L5 spinal cord of dorsal horn were collected, and then, Agilent Whole Mouse Genome Microarray 4×44K expression profiling were employed as a discovery platform to identify genes with the potential to provide basis for the clinical application of WTD for neuropathic pain. A 579-gene consensus signature was identified that distinguished between sham and SNL samples, and a 456-gene consensus signature was identified that distinguished between WTD and SNL samples. Expression of 12 genes (Crk1, Fgf13, Fgfr1, Crk1, Adrbk1, Erbb3, Gnas, Vegfa, Crk1, Erbb3, Drd2, Gnas) were identified as the efficacy of differentially expressed genes.
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Project description:Anti-tick vaccines represent a promising alternative to chemical acaricides for the management of ticks on wildlife; however little progress has been made to produce an effective vaccine in hosts relevant to tick reproduction. Further, most of the antigens described are expressed during feeding in domesticated hosts and may not activate the immune system in wild hosts. We recently tested Amblyomma americanum salivary (SG) and midgut (MG) extracellular vesicles (EVs) as vaccine candidates in white-tailed deer (Odocoileus virginianus; WTD), which resulted in on-host female tick mortality. Herein, we describe our efforts to identify the antigenic proteins found within these vesicles. Within both SG- and MG-EVs, an enriched “core- cargo” was identified within both SG- and MG-EVs, including chaperones, small GTPases, and other proteins previously reported in small EVs was discovered. Label-free quantitative proteomics showed significant differences in protein cargo between MG and SG-EVs (333 proteins out of 516). Serum from three vaccinated WTD (pre-vaccinated and day 57 post vaccination) and one control WTD was used to immunoprecipitated antigenic proteins from SG- and MG-EV preparations. Proteomic analysis of immunoprecipitated proteins identified seven antigenic proteins in SG-EVs and one in MG-EVs that were statistically significantly different from the pre-vaccinated serum. Moreover, these proteins were unique to vaccinated animals (not precipitated by control serums). Additionally, two MG-EVs and 24 SG-EV proteins show antigenic potential. These proteins represent promising candidates for anti-tick vaccine design in WTD and other wildlife.
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