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Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination

ABSTRACT: Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination

PROVIDER: PRJNA1303629 | ENA |

REPOSITORIES: ENA

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Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination

Project description:Background/Objectives: Synthetic mRNA vaccines have raised concerns regarding prolonged spike protein expression, immune activation, and potential off-target effects. This study investigates transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA COVID-19 vaccination. Methods: Bulk RNA sequencing was performed on peripheral blood from two patient groups: individuals with new-onset nonmalignant adverse events and individuals newly diagnosed with cancer post-vaccination. A control group of healthy individuals was used for comparison. Differential gene expression was analyzed using DESeq2, and Gene Set Enrichment Analysis (GSEA) was conducted using the MSigDB database and custom gene sets. Results: Both vaccine patient groups displayed widespread transcriptional dysregulation. In the nonmalignant adverse event group, hallmark enrichments included mitochondrial dysfunction, proteasome-mediated stress, transcriptomic instability, and systemic inflammation. The cancer group exhibited additional hallmarks of genomic instability, and epigenetic reprogramming. Nonsense-mediated decay (NMD), ribosomal stress, and MYC activation were prominent in both groups, while immune signaling via TLRs and type I interferons was particularly elevated in cancer patients.

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CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [mouse]

Project description:The mRNA vaccines against COVID-19 are highly effective yet associated with rare myocarditis cases, particularly in young males post-second dose. Here we explore the mediators of this adverse effect and its potential solutions, aiming to enhance the safety of future mRNA vaccines. Analysis of post-vaccination plasma highlighted a substantial increase in CXCL10 and IFN-γ levels in patients. Correspondingly, human iPSC-derived macrophages exposed to COVID-19 mRNA vaccines exhibited increased production of these two cytokines. iPSC-derived cardiomyocytes subjected to these cytokines exhibited impaired contractility, arrhythmogenicity, and myocarditis-like gene expression patterns. Genistein, an anti-inflammatory phytoestrogen, notably mitigated these effects, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocarditis. These findings underscore CXCL10 and IFN-γ as key mediators of myocarditis post-mRNA vaccination and propose genistein as a potential therapeutic to mitigate associated cardiovascular risks.

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CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [human]

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Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

Project description:Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

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Homo sapiens PBMCs: pre-vaccination (stimulation vs. no stimulation with EV71 antigen) vs. post-vaccination (stimulation vs. no stimulation with EV71 antigen)

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2020-01-31 | GSE144540 | GEO

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