Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1132302 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29718971.fastq.gz | Fastqsanger.gz | |||
| SRR29718972.fastq.gz | Fastqsanger.gz | |||
| SRR29718973.fastq.gz | Fastqsanger.gz | |||
| SRR29718974.fastq.gz | Fastqsanger.gz | |||
| SRR29718975.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptional pathways associated with aging were studied in circulating T follicular helper CD4 cells before and 7 days after influenza vaccination
2019-10-01 | GSE134416 | GEO
Project description:Virus infection induces T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the role of TH 1 cells is still elusive. IgG2 antibodies predominate in the response to vaccination with inactivated Influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAVs even in mice lacking TFH cells owing to B or T cell-specific ablation of the Bcl6. We demonstrate that IL-21 and IFN-γ secreted from TH1 cells were essential for greater persistence and higher titers of IgG2 protective antibodies. These results suggest that TH1 induction could be a promising strategy to induce effective neutralizing antibodies against emerging influenza viruses.
2016-10-12 | GSE85316 | GEO
Project description:COVID-19 mRNA vaccines generate high concentrations of circulating anti-Spike antibodies and Spike-specific CD4+ T cells following prime-boost vaccination. It is not yet clear if vaccine-induced CD4+ T cell responses in the draining lymph node contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we found large populations of Spike-specific CD4+ T follicular helper cells in the draining lymph node. A broadly immunodominant HLA-DPB1*04-restricted response to Spike166-180 composes one of the largest populations of T follicular helper cells in individuals with this allele, which is itself among the most common HLA alleles in the human population. Spike-specific T follicular helper cells are present in the lymph node 30 days after vaccine boost and persist in some individuals more than 170 days. Collectively, our results underscore the key role that robust T follicular helper cell responses play in the establishment of long-term immunity in this very efficacious human vaccine.
2022-01-04 | GSE183393 | GEO
Project description:The gut microbiome plays a crucial role in modulating human immunity. Previously, we found that antibiotic-induced microbiome perturbation affected influenza vaccine responses depending on pre-existing immunity levels. However, its impact on primary responses remains unclear. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration disrupted the microbiome, reducing gut bacterial load and causing long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced: 1) an enhanced pro-inflammatory signature early after vaccination, 2) a shift in the balance of vaccine-specific T-helper 1(Th1) to T-follicular-helper response towards Th1 phenotype, 3) profound alterations in metabolites, particularly in secondary bile acids in blood. By integrating multi-omics datasets, we generated a multi-scale, multi-response network that revealed key regulatory nodes including the microbiota, secondary bile acids, and humoral immunity to vaccination.
2025-06-01 | GSE294364 | GEO
Project description:Influenza virus vaccination remains the best strategy for combating virus infection, but vaccine efficacy is highly variable. An ideal influenza vaccine must have two attributes: one, it should be capable of inducing broadly cross-reactive antibodies that can neutralize diverse influenza virus strains; and two, it must induce long-lived antibody responses to maintain protective immunity for extended periods. Germinal center (GC) reactions are the major sites where diversification and affinity maturation of B cells occur. Whether a persistent GC response could expand the breadth of responding B cell clones following influenza vaccination in humans remains unknown. Here, we show that influenza virus vaccine-specific GC B cells persist for over nine weeks post vaccination in two out of seven individuals. These late vaccine-specific GC B cells exhibited increased somatic hypermutation (SHM) of their B cell receptors compared to early vaccine-specific GC B cells. After re-immunization with seasonal influenza virus vaccine, individuals with a persistent GC engaged vaccine-specific plasmablasts (PBs) with higher SHM frequency. Tracking the maturation of three clonally related GC B cell lineages over time revealed that late GC B cells had receptors that recognized and neutralized heterologous influenza virus strains. Thus, SHM induced by persistent GCs can broaden the antibody response to influenza virus vaccination. This indicates that seasonal influenza virus vaccination in humans can induce broadly cross-reactive antibodies that target diverse influenza virus strains.
2024-06-13 | GSE211869 | GEO
Project description:Influenza virus vaccination remains the best strategy for combating virus infection, but vaccine efficacy is highly variable. An ideal influenza vaccine must have two attributes: one, it should be capable of inducing broadly cross-reactive antibodies that can neutralize diverse influenza virus strains; and two, it must induce long-lived antibody responses to maintain protective immunity for extended periods. Germinal center (GC) reactions are the major sites where diversification and affinity maturation of B cells occur. Whether a persistent GC response could expand the breadth of responding B cell clones following influenza vaccination in humans remains unknown. Here, we show that influenza virus vaccine-specific GC B cells persist for over nine weeks post vaccination in two out of seven individuals. These late vaccine-specific GC B cells exhibited increased somatic hypermutation (SHM) of their B cell receptors compared to early vaccine-specific GC B cells. After re-immunization with seasonal influenza virus vaccine, individuals with a persistent GC engaged vaccine-specific plasmablasts (PBs) with higher SHM frequency. Tracking the maturation of three clonally related GC B cell lineages over time revealed that late GC B cells had receptors that recognized and neutralized heterologous influenza virus strains. Thus, SHM induced by persistent GCs can broaden the antibody response to influenza virus vaccination. This indicates that seasonal influenza virus vaccination in humans can induce broadly cross-reactive antibodies that target diverse influenza virus strains.
2024-06-13 | GSE211865 | GEO
Project description:People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and >13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.
2021-03-18 | GSE167893 | GEO
Project description:The goal of this study is to determine the impact of Tcf1 and Lef1 deficiency on T follicular helper (Tfh) cells elicited by protein immunization. We demonstrate that although phenotypic Tcf1/Lef1-deficient Tfh cells were able to develop in response to vaccination, they are functionally impaired. Mechanisc studies reveal the direct regulatory effect by Tcf1 and Lef1 on transcriptome and chromatin accessibility in vaccine-elicited Tfh cells. Analysis of chromatin accessibility in WT and Tcf1/Lef1-deficient Tfh cells eliciated by vaccination.
2020-10-19 | GSE146421 | GEO
Project description:Humoral immunity is orchestrated by follicular helper T (Tfh) cells, which promote cognate B cells to produce high-affinity, protective antibodies. In aged individuals, humoral immunity after vaccination is diminished despite the presence of Tfh cells, suggesting defects after initial Tfh formation. In this study, we utilized both murine and human systems to investigate how aging alters Tfh cell differentiation after influenza vaccination. We found that young Tfh cells underwent progressive differentiation after influenza vaccination, culminating in clonal expansion of effector-like cells in both draining lymph nodes and blood. In aging, early stages of Tfh development occurred normally. However, aging rewired the later stages of progressive development in Tfh cells, resulting in a transcriptional program reflective of cellular senescence, sustained pro-inflammatory cytokine production, and metabolic reprogramming. We investigated the extent to which this rewiring of aged Tfh cells is due to the age-associated inflammatory (“inflammaging”) microenvironment and found that this setting was sufficient to both block the transition of Tfh cells to a post-effector resting state and to skew Tfh cells towards a hyperinflammatory phenotype. Together, these data suggest that aging dampens humoral immunity by cytokine-mediated rewiring of late effector Tfh cell differentiation into an activated, yet dysfunctional, cellular state.
2025-04-30 | GSE286979 | GEO
Project description:Increased antibody affinity over time after vaccination is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown. Here we report that PC precursors (prePC) expressing high affinity antibodies received higher levels of T follicular helper (Tfh) and divided at higher rates than their lower affinity counterparts once they left the GC. Thus, differential cell division by selected prePCs accounted for how diverse precursors developed into a PC compartment that mediated serological affinity maturation.
2024-12-19 | GSE282284 | GEO