Lethal Cytokine Storm Post-mRNA Booster Vaccination
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PROVIDER: PRJNA1008117 | ENA |
REPOSITORIES: ENA
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Project description:Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response. Microarrays (Human Exon 1.0 ST Arrays (Affymetrix )) were used to compare the gene expression alteration following DTP-vaccination in 18-19 months old West African girls. The gene expression analysis was based on RNA from venous blood. The blood was drawn immediately before DTP-vaccination (baseline sample) and 6 weeks after (42 -50 days, post-vaccination sample) in a total of eight girls
2012-10-01 | E-GEOD-39017 | biostudies-arrayexpress
Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes prior to COVID-19 mRNA booster vaccination. D01 and D21 correspond to samples collected at pre-dose 1 and pre-dose 2 respectively. RNA was also extracted from blood collected at indicated time points post-vaccination. DB1, DB2, DB4 and DB7 correspond to booster day 1 (pre-booster), booster day 2, booster day 4 and booster day 7 respectively. The case subject experienced cardiac complication following mRNA booster vaccination. We performed gene expression analysis of case versus controls over time.
2023-03-20 | E-MTAB-12829 | biostudies-arrayexpress
Project description:SARS-CoV2 infection leads to cardiac injury and dysfunction in 20-30% of hospitalized patients and higher rates of mortality in patients with pre-existing cardiovascular disease. Inflammatory factors released as part of the 'cytokine storm' are thought to play a critical role in cardiac dysfunction in severe COVID-19 patients. Here we use human cardiac organoid technology combined with high sensitivity phosphoproteomics and single nuclei RNA sequencing to identify inflammatory targets inducing cardiac dysfunction. This new pipeline allowed rapid progress and identification of putative therapeutics. We identify a novel interferon-gamma driven BRD4 (bromodomain protein 4)-fibrosis/iNOS axis as a key intracellular mediator of inflammation-induced cardiac dysfunction. This axis is therapeutically targetable using BRD4 inhibitors, which promoted full recovery of function in human cardiac organoids and prevented severe inflammation and death in a cytokine-storm mouse model. The BRD inhibitor INCB054329 was the most efficacious, and is a prime candidate for drug repurposing to attenuate cardiac dysfunction and improve COVID-19 mortality in humans.
2022-02-21 | PXD020994 | Pride
Project description:Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response.
2012-10-01 | GSE39017 | GEO
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2017-03-24 | GSE67222 | GEO
Project description:SARS-CoV-2 spike (S) specific T-cell and antibody (AB) responses after primary BNT162b2 vaccination (Pfizer Inc., New York, NY, USA and BioNTech SE, Mainz, Germany) partially depend on the phenotypic composition of pre-existing T-helper (Th) cell populations (Saggau et al., 2022, Immunity). However, adaptive cellular responses and their impact on sustained immune protection after booster vaccination are incompletely understood. We therefore monitored cellular and humoral immune responses before and up to 6 months after the 3rd BNT162b2 vaccination to identify early determinants of sustained responses. As part of an ongoing registry study (Corona Registry Study number 20–426, approved by the ethics committee of the Ludwig Maximilians University Munich), volunteers were recruited among employees of the University Hospital of Augsburg. All subjects had received primary vaccination with two doses of BNT162b2 and were enrolled before their third dose of BNT162b2 (first booster). Exclusion criteria were active infections, receipt of immunomodulatory therapy, pregnancy, positive nucleocapsid-specific (N) IgG titers, and underlying conditions associated with significant impairment of anti-COVID-19 immunity (e.g., diabetes mellitus, cancer, prior stem cell transplantation, or autoimmune diseases). Lithium heparin-anticoagulated whole blood and serum samples were collected immediately before the third vaccination (T0), as well as 1 (T1), 3 (T3), and 6 months (T6) after booster vaccination. No additional booster doses were given during the study period. Serum samples were tested for nucleocapsid (N), S (COBAS e801 immunoassay analyzer with Elecsys Anti-SARS-CoV-2 and Anti-SARS-CoV-2 S (Hitachi Ltd., Tokyo, Japan and Roche Diagnostics GmbH, Basel, Switzerland), and neutralizing AB responses (Haselmann et al., 2020, Clin Chem Med Lab). Subjects developing N IgG or those with incomplete follow-up were excluded. Whole blood was stimulated with co-stimulatory factors anti-CD28 and anti-49d (1 µg/mL Miltenyi Biotec, Bergisch Gladbach, Germany) only, representing the unstimulated/background sample, or additionally S peptides (0.6 nMol/peptide/mL Prot_S, Miltenyi Biotec, Bergisch Gladbach, Germany), as described previously (Lauruschkat et al., 2021, J Fungi (Basel), Weis et al., 2020, Med Mycol). Samples were subsequently analyzed by flow cytometry (data not relevant for this file/analysis) and 13-plex multiplex cytokine assay (LegendPlex Essential Immune Response Panel, BioLegend, San Diego, USA). Significant associations between readouts were identified by multiple testing-adjusted rank correlation analysis. We found moderate correlation between S IgG (r=0.47), S-induced IL-2 (r=0.58) and IFN-γ (r=0.43) at T1 and T6. S IgG, S-induced IL-2, and S-induced IFN-γ at T6 were significantly associated with increased IL 2 & IL 4, IP 10 & MCP1, and IFN-γ & IP 10 levels at T1, respectively (data presented at the 7th Joint Microbiology & Infection Conference of the German Society for Hygiene and Microbiology (DGHM) and the Association for General and Applied Microbiology (VAAM), Wuerzburg, Germany). Subsequently, the preserved T1 RNA samples of the top and bottom half responders at T6 (based on S IgG, S-induced IL-2, and IFN-γ measurements) were isolated via RNeasy Plus Mini Kit (Qiagen, Hilden, Germany) and analyzed by nCounter Immune Exhaustion Panel (Nanostring, Seattle, USA) as described below. At the time of GEO submission of this data (August 2024), the associated manuscript is under review by Frontiers in Immunology.
2024-08-06 | GSE273994 | GEO
Project description:Prolonged sleep deprivation induces cytokine storm-like syndrome in mammals
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Project description:Acute cardiac injuries occur in 20%–25% of hospitalized COVID‐19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID‐19 hyperinflammation. As IL‐1β is an upstream cytokine and a core COVID‐19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID‐19 cytokine storm. The IL‐1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID‐19 hearts. The comparison of IL‐1β treated hCOs with cardiac tissue from COVID‐19 autopsies illustrated the critical roles of hyper‐inflammation in COVID‐19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL‐1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID‐19 cardiac in- juries at baseline and simulated exercise conditions.
2023-12-20 | GSE250520 | GEO
Project description:The study examined antibody and memory B cell responses to SARS-CoV-2 mRNA booster vaccination in the elderly and showed a decrease in memory B cell numbers with an altered antibody repertoire that may contribute to a higher risk for severe disease in the elderly.
2023-05-27 | GSE233230 | GEO
Project description:sn-RNAseq profiling of the impact of a cytokine storm model in human cardiac organoids
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