Ontology highlight
ABSTRACT:
PROVIDER: PRJNA807823 | ENA |
REPOSITORIES: ENA
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Project description:This experiment aims to profile polyclonal antibody binding profiles in serum from vaccinated animals relative to antibody function in a virus neutralization assay. Rabbits received three vaccinations with a DNA vaccine encoding the spike protein of the SARS-CoV-2 index strain. Serum samples were selected based on a three-tier (low, intermediate, and high) capacity to cross-neutralize SARS-CoV-2 strains with known neutralization resistance. Following normalization of total anti-spike IgG levels, serum of each animal (n=3) were evaluated for antibody binding to 10mer cyclic constrained peptides spanning the entire spike protein and regions with known SARS-CoV-2 variant of concern spike mutations.
2023-08-31 | E-MTAB-13040 | biostudies-arrayexpress
Project description:Virulent infectious agents such as SARS-CoV-2 and Methicillin Resistant Staphylococcus Aureus (MRSA) induce tissue damage that recruits neutrophils and monocyte/macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2 infected lungs, express phosphatidylinositol 3-kinase gamma (PI3K a signaling protein that coordinately controls granulocyte and monocyte trafficking to diseased tissues and immune suppressive, pro-fibrotic transcription in myeloid cells. PI3K deletion and inhibition with the clinical PI3K inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage and cytokine storm. These results demonstrate essential roles for PI3K in inflammatory lung disease and support the potential use of PI3K inhibitors to suppress inflammation in severe infectious diseases.
2024-03-12 | GSE255211 | GEO
Project description:SARS-CoV-2 infections induce aberrant pulmonary and systemic inflammation, vascular leak, coagulation and fatal organ damage. To identify therapeutic strategies to suppress COVID-19-associated inflammation, we sequenced lung tissue from sham infected mice and mice infected with SARS-CoV-2 that were treated with the cancer therapeutic IPI-549 (eganelisib) or vehicle. IPI-549 suppressed signatuers of pulmonary inflammation and reduced signatures of lung damage. These studies demonstrate the essential role of myeloid cells and PI3Kγ in SARS-CoV-2 inflammatory disease and support the use of myeloid cell inhibitors such as IPI-549 to suppress inflammation and promote survival in pulmonary infections like SARS-CoV-2.
2023-04-30 | GSE229570 | GEO
Project description:In the initial process of COVID-19, SARS-CoV-2 infects respiratory epithelial cells and then transfers to other organs via the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin (VE-cadherin)-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in a COVID-19 patient’s lungs were decreased. CLDN5 overexpression or Fluvastatin treatment could rescue the SARS-CoV-2-induced respiratory endothelial barrier disruption. We therefore concluded that the downregulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a novel therapeutic strategy against COVID-19.
2022-09-22 | GSE196113 | GEO
Project description:In the initial process of COVID-19, SARS-CoV-2 infects respiratory epithelial cells and then transfers to other organs via the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin (VE-cadherin)-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in a COVID-19 patient’s lungs were decreased. CLDN5 overexpression or Fluvastatin treatment could rescue the SARS-CoV-2-induced respiratory endothelial barrier disruption. We therefore concluded that the downregulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a novel therapeutic strategy against COVID-19.
2022-09-22 | GSE206635 | GEO
Project description:Human cardiac pericytes express the receptors for SARS-CoV-2 and contribute to microvascular dysfunction in COVID-19 patients. The SARS-CoV-2 capsid Spike protein seems to play a direct role in COVID-19 microangiopathy, but it is not known yet whether the Spike protein alone, without the infectious virus, can induce transcriptional alterations in pericytes. This study investigated the signalling pathways activated by the Spike protein in cultured human cardiac pericytes. We found that 309 RNA transcripts were significantly modulated in pericytes exposed to the Spike protein, with the upregulation of pathways linked to inflammation and viral infection.
2023-05-09 | GSE218644 | GEO
Project description:Previous studies have detected the presence of SARS-CoV-2 viral proteins in bronchial cartilage chondrocytes. We hypothesised that the leakage of viral proteins to local joint tissue was due to virus-induced endothelial dysfunction. Studies have also shown upregulation of endothelin-1 (ET-1), the most potent vasoconstrictor, in COVID patients. We are investigating the direct effect of SARS-CoV-2 spike protein (SP) and the host response to chondrocytes. Human mesenchymal stem cells (hMSCs)-differentiated chondrocytes were treated with either full-length SARS-CoV-2 spike protein (SP) only or a combination of spike protein, neutralising antibody to S1 and endothelin-1 (SAE) to mimic viral insult and host response respectively. RNA sequencing was performed to compared the change in transcriptome in control, SP and SAE. All samples were processed in the same batch. Default quality control parameters were used.
2024-05-08 | GSE267009 | GEO
Project description:Patients diagnosed with coronavirus disease 2019 (COVID-19) mostly become critically ill around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG in serum of critically ill COVID-19 patients induces hyper-inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more pro-inflammatory because of different glycosylation, particularly low fucosylation, of the Fc tail. Notably, low anti-spike IgG fucosylation normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fcγ Receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Finally, we demonstrate that the hyper-inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of the kinase, Syk.
2021-04-30 | E-MTAB-10431 | biostudies-arrayexpress
Project description:The experiment aims at characterizing the immune responses elicited by the BNT162b2 vaccine against SARS-CoV-2, initially administered in a two dose regimen (second dose after three weeks followinf the first dose) In particular the transcriptional landscape of circulating T and B lymphocytes has been profiled longitudinnaly by scRNA-seq coupleD with CITE-seq of 19 cell surface markers to better classify T cells subpopulations, LIBRA-seq to assess the Spike-specificity of BCRs and and V(D)J seq to also track T and B cell clones dynamics. Eeach sample was profiled before vaccination (T0), 21 days after the first dose (T1), 2 months after the first dose (1 month after the second dose) (T2). The immune responses were characterized using PBMC from 3 SARS-CoV-2 experienced donors (experiencing SARS-Cov-2 at least 4 months before the first vaccinatin) and 2 SARS-CoV-2 unexperienced donors.
2024-04-18 | E-MTAB-13721 | biostudies-arrayexpress
Project description:We generated LNP-mRNA encoding B.1.1.529 SARS-CoV-2 spike, and intramuscularly administered it in a human IgG and IgK knock-in mouse. Single cell VDJ-seq unveiled the sequences of human monoclonal antibodies targeting the B.1.1.529 SARS-CoV-2 spike protein.
2022-07-01 | GSE203030 | GEO