Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to vaccination

ABSTRACT: Single-cell RNA sequencing can to resolve transcriptional features from large numbers of individual immune cells, but techniques capable of resolving the variable regions of B cell receptors (BCR) – defining features that confer antigen specificity to B cells – remain limited, especially from widely-used 3`-barcoded libraries. Here, we report a method that for recovering paired, full-length variable region sequences of the BCRs from 3`-barcoded single-cell whole transcriptome libraries. We first verified this method could produce accurate, full-length BCR sequences. We then applied this method to profile antigen-specific B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in infant rhesus macaques. Using our method, we defined features of the BCR associated with specificity for the ST3 antigen and showed that these sequence characteristics are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and for profiling antigen-specific responses elicited by vaccination.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE232873 | GEO | 2023/05/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Full-length single-cell BCR sequencing paired with RNA sequencing reveals convergent responses to vaccination

Project description:Single-cell RNA sequencing can resolve transcriptional features from individual cells, but techniques capable of resolving the variable regions of B cell receptors (BCRs) – defining features that confer antigen specificity to B cells – remain limited, especially from widely-used 3`-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3`-barcoded single-cell whole transcriptome libraries. We applied this method to produce accurate, full-length BCR sequences from cDNA of human PBMC generated following the 10x Genomics 3`GEX protocol.

2024-07-07 | GSE266697 | GEO

Proteomic identification of anti-tetanus toxoid antibodies from human serum (HD1)

Project description:Proteomic identification and characterization of antibodies comprising the serological response to antigen can provide unique insight into the functional dynamics of adaptive immunity. We have developed a novel method to overcome the technical challenges which previously limited the direct analysis of immunoglobulin proteins in serum, as demonstrated by the identification of human anti-tetanus toxoid (TT) immunoglobulin G (IgG) proteins following booster vaccination. We analyzed the serum IgG repertoire across four time-points corresponding to pre-vaccination, 7 days, 3 months, and 9 months post vaccination. Antigen-specific antibodies were affinity purified against immobilized TT protein and sequenced by bottom-up nanoLC-MS/MS. Interpretation of mass spectra required a custom reference database of IgG heavy and light chain variable sequences determined by NextGen RNA sequencing of the donor's circulating plasmablasts and memory B cells following booster vaccination.

2014-04-24 | PXD000917 | Pride

TCR sequencing paired with massively parallel 3′ RNA-seq reveals clonotypic T cell signatures

Project description:High-throughput 3′ single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that confer antigen specificity. Here, we present a strategy that enables simultaneous analysis of TCR sequences and corresponding full transcriptomes from 3′-barcoded scRNA-seq samples. This approach is compatible with common 3′ scRNA-seq methods, and adaptable to processed samples post hoc. We applied the technique to identify transcriptional signatures associated with T cells sharing common TCRs from immunized mice and from patients with food allergy. We observed preferential phenotypes among subsets of expanded clonotypes, including type 2 helper CD4+ T cell (TH2) states associated with food allergy. These results demonstrate the utility of our method when studying diseases in which clonotype-driven responses are critical to understanding the underlying biology.

2019-11-19 | GSE136028 | GEO

Therapeutic vaccine induced plasma cell differentiation is defective upon persistent HBsAg stimulation [scRNA]

Project description:Background & Aims: The precise mechanism underlying the attenuation of the antigen-specific B cell response induced by therapeutic vaccination during chronic HBV infection remains unclear. The development of vaccines or strategies targeting this impediment through rational design could potentially result in significant advancements in the treatment of chronic hepatitis B. Methods: A mouse model with a knock-in of a B cell receptor specific to the hepatitis B virus surface antigen was generated under the name E6F6-B. This model was utilized to investigate the temporal and spatial patterns of humoral responses induced by therapeutic vaccination in the presence of persistent antigen stimulation. Through the use of multiple transcriptome sequencing techniques, the differentiation trajectory of HBsAg-specific B cells post therapeutic vaccination during chronic hepatitis B infection was elucidated. Results: In light of the E6F6-B transfer model, a significant reduction in antibody secreting cells were observed two weeks after vaccination. Additionally, an atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138-) was identified as a consequence of persistent BCR signaling in the absence of CD40 co-stimulation. A therapeutic antibody-induced suppression of BCR signaling revitalized the HBsAg-specific B cell response.

2024-04-28 | GSE230862 | GEO

Therapeutic vaccine induced plasma cell differentiation is defective upon persistent HBsAg stimulation [bulkRNA]

2024-04-28 | GSE230861 | GEO

Gene expression profile at single cell level of splenic antigen specific memory B-cells after immunization with the Fentanyl-VAST vaccine platform

Project description:Antigen specific memory B cells are considered as a homogeneous population. Here, we wanted to isolate antigen-specific memory cells from mice in order to both characterize the response to the immunization regimine and identify high-affinity candidate BCRs for expression. For this, we used single cell RNA sequencing (scRNA-seq) to describe the diversity of anti-fentanyl B cells elicited by a fentanyl-immunization platform and identify the different markers for each subbpopulation. We use this appoach to select the switched memory B cell, study their BCR repertoir and identify the BCR sequences from the most potent memory B cells.

2023-05-17 | GSE202173 | GEO

C5aR+ dendritic cells fine-tune the Peyer’s patch microenvironment to induce antigen-specific CD8+ T cells

Project description:The mucosa is an ideal route for vaccination against pathogen infection, but the effective adjuvant capable of overcoming the tolerogenic dendritic cell (DC) environment is unavailable. We characterized type 2 conventional DCs and lysozyme-expressing monocyte-derived DCs (LysoDCs) of Peyer’s patches to identify the vaccination target cells through single-cell RNA sequencing. Based on functional analysis of the data, we suggest that C5aR+ LysoDCs and Co1 peptide, a C5aR ligand, as a target cell and an adjuvant, respectively, for mucosal vaccination. Co1-mediated stimulation of C5aR+ LysoDCs increased the level of reactive oxygen species, leading to CCL3-mediated chemotaxis and exogenous antigen cross-presentation, which elicited an antigen-specific CD8+ T cell response. In a SARS-CoV-2 vaccine model, Co1 peptide increased the frequency of antigen-specific polyfunctional CD8+ T cells in systemic as well as mucosal compartments. Collectively, LysoDC activation by Co1 peptide potentiates vaccination efficiency by constructing an immunostimulatory environment in the mucosal immune inductive site.

2023-07-24 | GSE212701 | GEO

Comparable CD8 + T cell responses to SARS-CoV-2 vaccination in single-cell transcriptomics of recently allogeneic transplanted patients and healthy individuals

Project description:Despite extensive research on SARS-CoV-2 vaccination responses in healthy individuals, there is comparatively little known beyond antibody titers and T-cell responses in the vulnerable cohort of patients after allogeneic hematopoietic stem cell transplantation (ASCT). In this study, we assessed the serological response and performed longitudinal multimodal analyses including T cell functionality and single-cell RNA sequencing combined with TCR/BCR profiling in the context of BNT162b2 vaccination in ASCT patients. In addition, these data were compared to publicly available data sets of healthy vaccinees. Protective antibody titers were achieved in 40% of patients. We identified a distorted B and T cell distribution, a reduced TCR diversity, and increased levels of exhaustion marker expression as possible causes for the poorer vaccine response rates in ASCT patients. IGHV gene rearrangement after vaccination proved to be highly variable in ASCT patients. Changes in TCRα and TCRβ gene rearrangement after vaccination differed from patterns observed in healthy vaccinees as well as unvaccinated ASCT patients and associated transplant donors. Crucially, ASCT patients elicited comparable proportions of SARS-CoV-2 vaccine-induced (VI) CD8+ T cells, characterized by a distinct gene expression pattern that is associated with SARS-CoV-2 specificity in healthy individuals. Our study underlines the impaired immune system and thus the lower vaccine response rates in ASCT patients. However, since protective vaccine responses and VI-CD8+ T cells can be induced in part of ASCT patients, our data advocate early post-transplant vaccination due to the high risk of infection in this vulnerable group.

2024-03-07 | GSE253948 | GEO

Project description:BCR sequencing following MMR vaccination

| PRJNA1087553 | ENA

Synergically enhanced anti-tumor immunity of in vivo CAR by vaccination-elicited antibody-mediated cellular cytotoxicity boosting

Project description:Chimeric Antigen Receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies. However, it is limited to individualized cell therapy and faces challenges, including high costs, extended preparation time, and limited efficacy against solid tumors. Here, we generated circular RNAs (circRNAs) encoding Chimeric Antigen Receptor (CAR) transmembrane proteins, referred to as circRNACAR, which mediated remarkable tumor killing in both T cells and macrophages. In addition, macrophages exhibited efficient phagocytosis of tumor cells and pro-inflammatory polarization induced by circRNACAR in vitro. We demonstrated that circRNACAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), significantly inhibited tumor growth, improved survival rates and induced a pro-inflammatory tumor microenvironment in mice. Importantly, the combination of circRNAAnti-HER2-CAR and circRNA-based cancer vaccines encoding the corresponding transmembrane HER2 antigen, termed circRNAHER2, exhibited synergistically enhanced anti-tumor activity. Notably, we found that circRNACAR could boost the level of circRNAHER2-elicited antibodies, which could mediate effective killing of HER2+ tumor cells by macrophages, indicating the potential of vaccination-elicited antibodies in developing novel immunotherapy. This proof-of-concept study demonstrated that the combination of circRNA-based in vivo CAR and vaccines, termed in vivo CAR-VAC, holds the potential to become an upgraded off-the-shelf immunotherapy, and also sheds light on the huge potential of vaccination-elicited antibodies in cancer immunotherapy.

2024-05-22 | GSE268105 | GEO

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