Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination [CITE-Seq]
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ABSTRACT:
PROVIDER: PRJNA913899 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22811900.fastq.gz | Fastqsanger.gz | |||
| SRR22811901.fastq.gz | Fastqsanger.gz | |||
| SRR22811902.fastq.gz | Fastqsanger.gz | |||
| SRR22811903.fastq.gz | Fastqsanger.gz | |||
| SRR22811904.fastq.gz | Fastqsanger.gz |
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Project description:RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (ICR) 6.7-18.1%) compared to the overall memory B-cell repertoire (median 1.3%; ICR 0.9-2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
2022-12-22 | GSE221319 | GEO
Project description:RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (ICR) 6.7-18.1%) compared to the overall memory B-cell repertoire (median 1.3%; ICR 0.9-2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
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Project description:Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination
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Project description:Class switch towards non-inflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination [scRNA-Seq]
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Project description:Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells in a variety of organs. Clinical presentation is heterogeneous and pathophysiological mechanisms of IgG4-related autoimmunity remain elusive. Secondary parenchymal lesions of IgG4-RD in the central nervous system (CNS) are rare and there are very few cases of IgG4-RD with isolated CNS manifestation. Patients suffering from IgG4-RD frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an unusual inflammatory intracranial pseudotumor we provide novel insights into the immuno-pathophysiology of IgG4-RD by illustrating an IgG4-RD-associated polyclonal T cell response in the CSF and multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells.
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Project description:Transcriptome analysis in patients with IgG4-RD and healthy controls IgG4-related disease (IgG4-RD) is a new emerging disease entity characterized by elevated serum IgG4 concentrations and tissue tumefaction or infiltration by IgG4-positive plasma cells. At present, however, it is not clear whether IgG4-RD is caused by abnormalities in acquired immunity, like autoimmune diseases, or whether the excess production of IgG4 is a true cause of IgG4-RD or an epiphenomenon associated with inflammatory and/or allergic reactions. We therefore attempted to identify genes related to the pathogenesis or clinicopathology of IgG4-RD. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed to screen for genes showing changes in expression. To exclude any gender-related differences in gene expression, DNA microarray analysis was performed only on samples obtained from male patients and controls. Total RNA was reverse transcribed to cDNA using AmbionM-BM-. WT Expression kits (Applied Biosystems, Foster City, CA), labeled with GeneChipM-BM-. WT Terminal Labeling and Controls kits (Affymetrix, Santa Clara, CA), and hybridized to GeneChipM-BM-. Human Gene 1.0 ST Arrays (Affymetrix), which include 28869 probes. Digitalized image data were processed using GeneChipM-BM-. Operating Software (Affymetrix).
2015-03-03 | E-GEOD-66465 | biostudies-arrayexpress
Project description:The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. A comprehensive analysis of 2,565 miRNAs was performed in biopsied specimens and serum of 17 cases with IgG4-ROD and 21 cases with orbital MALT lymphoma. We identified specific miRNA signatures, their miRNA target pathways, and network analysis associated with IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. In the tissue pathway, Longevity regulating pathway in IgG4-ROD and MAPK signaling pathway in orbital MALT lymphoma were most enriched by downregulated miRNAs. This is the first evidence of the miRNA profile in biopsied specimens and serum of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating of these disorders.
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Project description:Single-cell RNA-sequencing (scRNA-Seq) is widely used to characterize immune cell populations. However, mRNA levels correlate poorly with expression of surface proteins, which are well established to define immune cell types. CITE-Seq (cellular indexing of transcriptomes and epitopes by sequencing) utilizes oligonucleotide-tagged antibodies to simultaneously analyze surface phenotypes and transcriptomes. Considering the high costs of adding surface phenotyping to scRNA-Seq, we aimed to determine which of 188 tested CITE-Seq antibodies can detect their antigens on human peripheral blood mononuclear cells (PBMCs), a commonly interrogated cell population in immunology, and find the optimal concentration for staining. The recommended concentration was optimal for 76 antibodies, whereas staining quality of 7 antibodies improved when the concentration was doubled. 33 and 8 antibodies still worked well when the concentration was reduced to 1/5 or 1/25, respectively. 64 antigens were not detected at any antibody concentration. Optimizing the antibody panel by removing antibodies not able to detect their target antigens and adjusting concentrations of the remaining antibodies could enable a cost reduction of almost 50%. In conclusion, our data are a resource for building an informative and cost-effective panel of CITE-Seq antibodies and use them at their optimal concentrations in future CITE-seq experiments on human PBMCs.
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