Human immunodeficiency virus 1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA495005 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7976536.fastq.gz | Fastqsanger.gz | |||
| SRR7976537.fastq.gz | Fastqsanger.gz | |||
| SRR7976538.fastq.gz | Fastqsanger.gz |
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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: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. Keywords: Time course - pre and post HPV immunizaton
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Project description:A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4+ T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of theses vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. High-resolution tandem mass spectrometry identified 131 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. Together with immunostaining and microscopy results, these data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing and cross-presentation. These observations may help explain the broad and cross-reactive immune responses generated by these vaccines.
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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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