Gene expression signatures to the radiation attenuated Schistosome Vaccine
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PROVIDER: PRJNA688890 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression signatures to the radiation attenuated Schistosome Vaccine
| PRJNA922116 | ENA
Project description: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).
2024-01-05 | GSE222444 | GEO
Project description:The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully characterized. In order to identify genes and pathways underlying protection we investigated patterns of gene expression in PBMC and skin draining Lymph Nodes (LN) from mice using two exposure comparisons: vaccination with 500 attenuated cercariae versus infection with 500 normal cercariae; one versus three doses. Vaccinated mice were challenged with 120 normal parasites. Integration of PBMC and LN data from the infected group revealed early up-regulation of pathways associated with Th2 skewing and polarization of IgG antibody profiles. Additionally, hemostasis pathways were downregulated in infected mice, correlating with platelet reduction, potentially a mechanism to assist parasite migration through capillary beds. Conversely, up regulation of such mechanisms after vaccination may explain parasite blockade in the lungs. In contrast, a single exposure to attenuated parasites revealed early establishment of a Th1 bias (signaling of IL-1, IFN-γ; and Leishmania infection). Genes encoding chemokines and their receptors were more prominent in vaccinated mice, indicating an enhanced capacity for inflammation, potentially augmenting the inhibition of intravascular migration. Increasing the vaccinations from one to three did not dramatically elevate protection, but there was a clear shift towards antibody-mediated effectors. However, elements of the Th1 bias were still evident. Notable features after three vaccinations were markers of cytotoxicity (including IL-6 and NK cells) together with growth factors and their receptors (FGFR/VEGF/EGF) and the apoptosis pathway. Indeed, there is evidence for the development of anergy after three vaccinations, borne out by the limited responses detected in samples after challenge. We infer that persistence of a Th1 response puts a limit on expression of antibody-mediated mechanisms. This feature may explain the failure of multiple doses to drive protection towards sterile immunity. We suggest that the secretions of lung stage parasites would make a novel cohort of antigens for testing in protection experiments.
2021-01-01 | GSE164094 | GEO
Project description:ETEC wild types and attenuated vaccine strains
| PRJEB2286 | ENA
Project description:Impact of live attenuated F. tularensis vaccine (DVC-LVS) on PBMC poly(A)-RNA expresssion in 10 subjects over time (Days 1, 2 ,7, and 14 post-vaccination) relative to pre-vaccination (Day 0).
2020-06-30 | GSE149809 | GEO
Project description:In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulate a potent cytotoxic T cells immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma (HCC) and colorectal cancer (CRC).
2022-10-27 | PXD031295 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE6871: Gene expression signatures that predict radiation exposure (human) GSE6873: Gene expression signatures that predict radiation exposure (mouse) Keywords: SuperSeries Refer to individual Series
2010-06-12 | E-GEOD-6874 | biostudies-arrayexpress
Project description:Transcriptomic responses to a live-attenuated Francisella tularensis vaccine
| PRJNA630207 | ENA
Project description:Enterotoxigenic Escherichia coli (ETEC) infections are a common cause of diarrheal illness in low- and middle-income countries. The live-attenuated ACE527 vaccine, adjuvanted with double mutant LT (dmLT), affords clear but partial protection against ETEC challenge inhuman volunteers. Comparatively, initial wild-type ETEC challenge completely protects against severe diarrhea on homologous re-challenge...To investigate molecular determinants of protection, vaccine antigen content was compared to wild-type ETEC, and proteome microarrays were used to assess immune responses following vaccination and ETEC challenge... Although molecular interrogation of the vaccine confirmed expression of targeted canonical antigens, relative to wild-type ETEC, vaccine strains were deficient in production of flagellar antigens, immotile, and lacked production of the EtpA adhesin. Similarly, vaccination ± dmLT elicited responses to targeted canonical antigens, but relative to wild-type challenge, vaccine responses to some potentially protective non-canonical antigens including EtpA were diminished or absent...These studies highlight important differences in vaccine and wild-type ETEC antigen content and call attention to distinct immunologic signatures that could inform investigation of correlates of protection, and guide vaccine antigen selection for these pathogens of global importance.
2019-07-25 | GSE134792 | GEO
Project description:The reasons for differences in vaccine effectiveness between live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are not clea Blood samples were obtained before vaccination and at days 7 and 21 postvaccination with 2015-2016 quadrivalent IIV or LAIV. Serologic response to the vaccine was measured by hemagglutination inhibition assay. Targeted RNA sequencing and serum cytokine analysis were performed. Paired analyses were used to determine gene expression and were compared between IIV and LAIV recipients.
2019-03-05 | GSE127792 | GEO