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Gene expression signatures to the radiation attenuated Schistosome Vaccine

ABSTRACT: Despite several decades of research, an effective vaccine against schistosomiasis remains elusive. The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully elucidated.Transcriptomic data of PBMC from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination, and Day 7 post-challenge) were reanalyzed. In addition, we generated data on PBMC collected 35 days after a high dose infection of 500 cercariae. Gene co-expression networks and Over Representation Analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING and the hub proteins for each module were identified using Cytoscape.Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to Th2 immune response; and a module (M6) associated with the vaccination process, displaying pathways related to Th1 response, CD8+ T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module hub revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2; and the (M6) vaccination module presented Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21. Our data point out to the potential role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21).

ORGANISM(S): Mus musculus

PROVIDER: GSE222444 | GEO | 2024/01/05

REPOSITORIES: GEO

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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.

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Gene expression signatures to the radiation attenuated Schistosome Vaccine

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