Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24707000_1.fastq.gz | Fastqsanger.gz | |||
| SRR24707000_2.fastq.gz | Fastqsanger.gz | |||
| SRR24707001_1.fastq.gz | Fastqsanger.gz | |||
| SRR24707001_2.fastq.gz | Fastqsanger.gz | |||
| SRR24707002_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 226 |
Similar Datasets
Project description:The soaring global monkeypox cases lead to a surge in demand for monkeypox vaccine, which far exceeds the supply. mRNA vaccine has achieved great success in prevention of coronavirus disease and holds promise against diverse pathogens. In this study, we generate a polyvalent lipid nanoparticle (LNP) mRNA vaccine candidate for monkeypox virus (MPXV) and evaluate its immunogenicity in animal models. This polyvalent MPXV mRNA vaccine candidate, MPXVac-097, encodes five 2022 MPXV targets that are important surface antigens. Three-dose (prime-boost-booster) MPXVac-097 vaccination elicits strong antibody response to A35R and E8L antigens, moderate response to M1R, but not B6R or A29, highlighting the differences in immunogenicity. Bulk T cell receptor (TCR) sequencing reveals preferential usage of VJ combinations and clonal expansion of peripheral T cells after MPXVac-097 vaccination. These data demonstrate initial feasibility of developing MPXV mRNA vaccine and pave the way for its future optimization.
2023-02-13 | GSE225183 | GEO
Project description:Cancer peptide vaccination represents a promising therapeutic approach, but has been hampered by lack of suitable antigens and restricted applicability due to different HLA backgrounds of individual patients. We here introduce a novel warehouse-based concept for composition of personalized peptide vaccines and report on its successful application in a Phase II clinical trial in patients with chronic lymphocytic leukemia (CLL) after first-line therapy. 26 CLL patients in at least partial remission (PR) after 6 months of immuno-chemotherapy were vaccinated with a personalized vaccine compiled from a premanufactured peptide warehouse comprising immunopeptidome-defined CLL-associated peptides. Primary objective was evaluation of immunogenicity, secondary objectives were safety and minimal residual disease (MRD) response. Immunopeptidome-guided vaccine composition was throughout successful, proving the feasibility of warehouse-based vaccine design. Vaccination was well tolerated, with local injection site reactions being the most common adverse event. Only few patients showed vaccine-induced T cell responses, attributable to their inability to mount strong immune responses due to immunechemotherapy and lack of potent adjuvant formulations. Both issues are addressed within a follow-up trial (NCT04688385), combining the immunopeptidome-guided warehouse-based vaccine design reported here with a potent novel adjuvant evaluating personalized multi- peptide vaccination in CLL patients under T cell supportive BTK inhibitor therapies.
2024-11-08 | PXD054248 | Pride
Project description:Cancer is characterized by an accumulation of somatic mutations, of which a significant subset can generate cancer-specific neoepitopes that are recognized by autologous T cells. Neoepitopes are emerging as important targets for cancer immunotherapy, including personalized cancer vaccination strategies. We used whole-exome and RNA sequencing analysis to identify potential neoantigens for a patient with non-small cell lung cancer. Sequencing revealed a low tumor mutational burden: 2,219 sequence variants were identified from the primary tumor, of which 23 were expressed in the transcriptome, involving 18 gene products. We assessed autologous T-cell reactivity to the candidate neoantigens using a long peptide approach and could demonstrate spontaneous T-cell responses to 5/18 (28%) mutated gene variants. Further, analysis of the TCR repertoire of neoantigen-specific CD4+ and CD8+ T cells revealed TCR clonotypes that were expanded in both blood and tumor tissue. In parallel, the 18 gene variants were incorporated into a Modified Vaccinia Ankara-based vaccine, which was evaluated in the transgenic HLA-A*02-restricted HHD mouse model. Following vaccination, de novo T-cell responses were generated to 4/18 (22%) mutated gene variants, of which 2 were also observed in the autologous setting; we determined the MHC restriction of the T-cell responses and used in silico prediction tools to determine the likely neoepitopes. Our study demonstrates the feasibility of efficiently identifying tumor-specific neoantigens that can be targeted by vaccination in tumors with a low mutational burden, and promises successful clinical application, with trials currently underway.
2022-04-27 | GSE179879 | GEO
Project description:SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) alpha/beta sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. In donors exhibiting sustained anti-S antibody titers (designated as “sustainers”), S-reactive T cell clonotypes detected immediately after 2nd vaccination polarized to follicular helper T (Tfh) cells, which was less obvious in “decliners”. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh cells upon vaccination contributes to the longevity of anti-S antibody titers.
2023-12-18 | GSE246535 | GEO
Project description:Influenza viruses (IV) infection is a public health concern worldwide. Currently, all available vaccines as well as antiviral drugs that target the virus itself are prone to resistance. Lessons learned from previous pandemic outbreaks is that people with a preexisting cellular immune response are either protected or developed less severe disease against the infection. Understanding CD8+ T cell immunity to IV across prominent HLA types is pivotal to rationally designing a universal influenza vaccine and generating protective immunity, especially for high-risk populations. Using mass spectroscopy, an immunopeptidomics analysis was carried out to characterize the entire landscape of peptides presented by MHC-I molecules post IV infection at different time points. We were able to identify sixteen naturally-presented MHC-I ligands restricted to different HLA allotypes including HLA-A*68, HLA-A*24, HLA-B*51, and HLA-B*07. Of these, nine peptides were immunogenic with multifunctional memory CD8 T cell response in different donors. These results highlight novel broadly protective IAV-derived CD8+ epitopes that reflect physiological peptide processing and presentation mechanisms that can work cooperatively with other distinct epitopes to provide optimal protection in particular against the newly-emerging variants.
2024-05-22 | PXD035241 | Pride
Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated immune responses in adult individuals pre and 8 months post BCG vaccination. We specifically determined changes in gene expression, cell subset composition, DNA methylome, and the TCR repertoire induced in PBMCs and CD4 memory T cells associated with antigen stimulation by either BCG or a Mycobacterium tuberculosis (Mtb)-derived peptide pool. Following BCG vaccination, we observed increased frequencies of CCR6+ CD4 T cells, which includes both Th1* and Th17 subsets, and mucosal associated invariant T cells (MAITs). A large number of immune response genes and pathways were upregulated post BCG vaccination with similar patterns observed in both PBMCs and memory CD4 T cells, thus suggesting a substantial role for CD4 T cells in the cellular response to BCG. These upregulated genes and associated pathways were also reflected in the DNA methylome. We described both qualitative and quantitative changes in the BCG-specific TCR repertoire post vaccination, and importantly found evidence for similar TCR repertoires across different subjects. The immune signatures defined herein can be used to track and further characterize immune responses induced by BCG, and can serve as reference for benchmarking novel vaccination strategies.
2021-12-23 | GSE188586 | GEO
Project description:To further characterize the T cell response to the neoantigen vaccine, we performed single-cell RNA and T cell receptor (scRNA/TCR-seq) of peripheral blood T cells at the 12-week post-vaccination time point.
2024-05-17 | GSE255830 | GEO
Project description:γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.
2024-03-04 | GSE260763 | GEO
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:Selecting superior de novo transcriptome assemblies: lessons learned by leveraging the best plant genome
| PRJNA301055 | ENA