Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike

ABSTRACT: Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigated the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We found that ~82% of SARS-CoV-2 S-reactive B cells show a naive phenotype, which represents an unusually high fraction of total human naive B cells (~0.1%). Approximately 10% of these naive S-reactive B cells shared an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196820 | GEO | 2022/06/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Characterization of B-cell receptor repertoire associated with asymptomatic and symptomatic infections of SARS-CoV-2

Project description:The immune responses to SARS-CoV-2 infections are very complex and remain to be further characterized. In this study, we performed the single-cell B-cell receptor (BCR) sequencing (scBCR-seq) of the PBMC samples from the healthy controls and SARS-CoV-2 infected individuals with various clinical presentations, and subsequently analyzed the abundance, diversity and difference of BCR repertoire in different groups of COVID-19 patients and the healthy controls, respectively. We identified a number of unique heavy or light chain VDJ genes pairs and combinational preference in each group, such as IGKV3-7 enriched in the asymptomatic subjects, whereas IGHV3-23-IGHJ4, IGHV1-18–IGLV3-19, IGHV1-18–IGLV3-21, and IGHV1-1–IGLV3-25 enriched in the recovery patients from the severe diseases. These findings may advance our understanding of the B-cell mediated immune responses to SARS-CoV-2 infections and help develop novel vaccine candidates and therapeutic antibodies against COVID-19.

2022-09-15 | GSE180118 | GEO

Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization

Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against SARS-CoV-2. Previous studies have shown divergent results regarding protective or damaging immunity induced by prior exposure to sCoVs. It is still unknown whether pre-existing humoral immunity may play a role in the vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera in healthy volunteers before and after immunization with inactivated SARS-CoV-2 vaccines, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level before vaccine immunization, as well as the relationship between pre-existing sCoVs immunity and vaccine-induced neutralization.

2021-10-13 | E-MTAB-11084 | biostudies-arrayexpress

Pre-existing cross-reactive antibody responses do not significantly impact inactivated COVID-19 vaccine-induced neutralization

2021-10-29 | E-MTAB-11117 | biostudies-arrayexpress

Mosaic RBD nanoparticle elicits immunodominant antibody responses across sarbecoviruses

Project description:Universal vaccines cross-protecting against sarbecoviruses including SARS-CoV-2 are in great need under continuous emergence of SARS-CoV-2 variants and potential novel coronavirus. Nanoparicle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) proteins from SARS-CoV-2 and other sarbecoviruses were used for preparedness to emergent zoonotic outbreak. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. The mosaic LuS-RBD vaccines induced cross-reactive binding and neutralizing antibody responses to sarbecoviruses. Single B cell sequencing revealed that mosaic LuS-RBD elicited B-cell receptor (BCR) repertoire using an immunodominant germline gene pair of IGHV14-3: IGKV14-111 in mice. Most of the tested IGHV14-3: IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to the clade 1a, 1b and 3 sarbecoviruses. By antibody binning and cryo-electron microscopy, we determined a reprensentative IGHV14-3: IGKV14-111 mAb, M2-7, bound to an conserved epitope on RBD largely overlapping with a pan-sarbecovirus mAb S2H97, which suggested that mosaic nanoparticles expended B cells recognizing the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticle against emerging sarbecoviruses.

2024-05-12 | GSE240940 | GEO

Influence of immunoglobulin genotypes on the elicitation of SARS CoV-2 neutralizing antibodies

Project description:The human immunoglobulin heavy chain (IGH) locus is exceptionally polymorphic with high allelic diversity of variable (V) genes and structural variation affecting large regions of the locus. Thus, our germline IGHV gene and allele content is highly personal, which may influence how we respond to infections and vaccinations. Here, we coupled individualized IGHV genotyping with the isolation of monoclonal antibodies against the SARS-CoV-2 spike, focusing on the IGHV1-69 and IGHV3-30 group of genes, which were over-represented in spike-specific B cells. These genes are characterized by both allelic and copy number variations, making them ideal for expanding our understanding of inter-individual differences in antigen-specific antibody responses. We found that for the IGHV1-69*20-using CAB-I47 antibody, the allele usage was critical as germline reversion to other, highly similar, IGHV1-69 alleles abolished the neutralizing activity. Our results demonstrate that as little as single nucleotide differences between different alleles can greatly influence the biological response.

2023-03-11 | PXD031945 | Pride

Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19

Project description:The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present a large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T helper (TH)1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.

2020-10-06 | GSE152522 | GEO

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis

Project description:Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines, yet the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated the systemic immunopathological landscape underlying such rare cases of myopericarditis occurring after SARS-CoV-2 LNP-mRNA vaccination using peripheral blood single-cell transcriptome and repertoire sequencing, among other multimodal approaches.

2023-05-04 | GSE230227 | GEO

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Project description:Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

2023-01-16 | GSE222872 | GEO

Comparative Pathogenesis of Three Human and Zoonotic SARS-CoV Strains in Cynomolgus Macaques

Project description:The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. Host responses to the three SARS-CoV strains were similar and only apparent early during infection with the majority of genes associated with interferon signalling pathways.This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use 4 strains, time course, lungs

2011-08-31 | E-GEOD-23955 | biostudies-arrayexpress

Absence of host innate immune responses in SARS-CoV-infected ferrets upon subsequent challenge

Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.

2013-05-28 | E-GEOD-11704 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data