Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA205279 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Immune responses are tightly regulated, yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live attenuated vaccine induces not only an adaptive immune response against tuberculosis, but also triggers innate immune activation and memory. We established personal immune profiles and chromatin accessibility maps over a time course of BCG vaccination in 323 individuals. This large resource uncovered genetic and epigenetic predictors of baseline immunity and BCG vaccine response. We found that BCG vaccination enhances the innate immune response only in individuals with dormant immune states at baseline, suggesting that exogeneous induction of trained immunity is not a universal booster of innate immunity, but specifically elevates weak innate immune responses. This study advances our understanding of BCG’s heterologous immune-stimulatory effects and trained immunity in humans. Moreover, our results highlight the value of epigenetic cell states as an “endophenotype” that connects immune function with genotype and the environment.
2024-01-08 | GSE241092 | GEO
Project description:Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying immunological responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+ NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
2023-11-08 | GSE247276 | GEO
Project description:Pneumococcal infections cause serious illness and death among older adults. A capsular polysaccharide vaccine PPSV23 (Pneumovax®) and a conjugated polysaccharide vaccine PCV13 (Prevnar®) are used to prevent these infections, yet underlying immunological responses, and baseline predictors remain unknown. We recruited and vaccinated 39 older adults (>60 years) with PPSV23 or PCV13. Both vaccines induced strong antibody responses at day 28 and similar plasmablast transcriptional signatures at day 10, however, their baseline predictors were distinct. Analyses of baseline flow cytometry and RNA-seq data (bulk and single cell) revealed a novel baseline phenotype that is specifically associated with weaker PCV13 responses, characterized by i) increased expression of cytotoxicity-associated genes and increased CD16+ NK frequency; ii) increased Th17 and decreased Th1 cell frequency. Men were more likely to display this cytotoxic phenotype and mounted weaker responses to PCV13 than women. Baseline expression levels of a distinct gene set was predictive of PPSV23 responses. This first precision vaccinology study for pneumococcal vaccine responses of older adults uncovered novel and distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
2023-11-08 | GSE247277 | GEO
Project description:A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention.
2014-04-10 | GSE47353 | GEO
Project description:A major goal of systems biology is the development of models that accurately predict responses of a cell or organism to perturbation. Constructing such models requires collection of dense measurements of system states, yet transformation of the data into predictive constructs remains a challenge. As a first step towards modeling human immunity, we have analyzed immune parameters in depth both at baseline and in response to perturbation with influenza vaccination. Peripheral blood cell transcriptomes, serum titers, frequencies of 126 cell subpopulations, and B cell responses were assessed before and after vaccination in 63 individuals and used to develop a systematic, computational framework to dissect inter- and intra-individual variation and build predictive models of post-vaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation parameters alone, which were validated using data from independent baseline time-points. Most of the parameters contributing to prediction delineated temporally-stable baseline differences across individuals, raising the prospect of immune responsiveness prediction before intervention. According to CHI protocol 09-H1-0239, PBMC samples from 63 healthy voluntiers were collected 7 days prior to vaccination, immediately before vaccination (day0), and at 3 time points (day1, day7 and day70) post vaccination. The CHI Consortium
2014-04-10 | E-GEOD-47353 | biostudies-arrayexpress
Project description:Mechanisms of poor responses to vaccines remain unknown. Hepatitis B virus-naïve elderly subjects received three vaccines, including a vaccine against hepatitis B virus (HBV). Pre-vaccination high dimensional analyses of blood using transcriptional profiling and flow cytometry revealed that subjects having increased memory B cell frequencies and higher expression of genes downstream of B cell receptor signaling responded more strongly to the HBV vaccine whereas subjects having higher expression of inflammatory related genes and greater numbers of activated innate immune cells showed a weaker response to this vaccine. The heme-induced response was associated with the poor response to the hepatitis B vaccine. Transcriptional profiling and flow cytometry results were validated in a distinct set of elderly subjects with accuracy greater than 60%. Our study is the first that identifies baseline predictors of responses to vaccines in a population of subjects known to be highly susceptible to infections.
2016-01-09 | GSE65834 | GEO
Project description:High-resolution analyses of global human Y chromosome and mtDNA variation
| PRJEB4417 | ENA
Project description:Dendritic cells (DCs) are central regulators of both innate and adaptive immunity and play roles in processes ranging from antitumor immunity to host-microbiome communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses and to deploy DCs for immunotherapy. Here, we develop a CRISPR/Cas9 genome editing method for human monocyte-derived DCs (moDCs) with a median knockout efficiency of >93% across >300 genes. Using this method, we perform arrayed genetic screens in moDCs, identifying mechanisms by which human immune cells tune responses to lipopolysaccharides (LPSs) from the human microbiome. In addition, we reveal donor-specific responses to LPSs, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify genes that control this specificity, highlighting the potential of our method to pick apart genetic determinants of inter-individual variation in immune responses.
2021-04-27 | GSE161466 | GEO
Project description:Dendritic cells (DCs) are central regulators of both innate and adaptive immunity and play roles in processes ranging from antitumor immunity to host-microbiome communication at mucosal surfaces. It remains difficult, however, to genetically manipulate human DCs, limiting our ability to probe how DCs elicit specific immune responses and to deploy DCs for immunotherapy. Here, we develop a CRISPR/Cas9 genome editing method for human monocyte-derived DCs (moDCs) with a median knockout efficiency of >93% across >300 genes. Using this method, we perform arrayed genetic screens in moDCs, identifying mechanisms by which human immune cells tune responses to lipopolysaccharides (LPSs) from the human microbiome. In addition, we reveal donor-specific responses to LPSs, underscoring the importance of assessing immune phenotypes in donor-derived cells, and identify genes that control this specificity, highlighting the potential of our method to pick apart genetic determinants of inter-individual variation in immune responses.
2021-04-27 | GSE161401 | GEO
Project description:In this study we wanted to identify baseline predictors of successful vedolizumab therapy in patients with inflammatory bowel disease.
2019-08-23 | E-MTAB-7845 | biostudies-arrayexpress