Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults [scRNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247277 | GEO | 2023/11/08
REPOSITORIES: GEO
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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:The investigation includes findings from our clinical trial, monitoring individualized response to pneumococcal vaccination, where we have carried out integrative profiling assessment of saliva pre and post vaccination in a single individual. This is to our knowledge the most extensive saliva-centered omics dataset on an individual, covering 100 timepoints over the course of one year. The time span covers a healthy period as well as comprehensive monitoring of innate and adaptive immune responses following pneumococcal vaccination. Protein and RNA from saliva were produced at each timepoint (100 timepoints), and mass spectrometry proteomics and RNA-sequencing were carried out for all samples in non-targeted comprehensive profiling. Specifically, a single individual (male, 38) was profiled over multiple timepoints during healthy periods, as well as post treatment with pneumococcal vaccine (PPSV23). Initially pre-immunization samples, including a 24 hour period with hourly sampling (samples P1052515H07-P1052615H08), were collected to provide a comparative baseline. A subsequent 24-hour time course was performed, with again hourly samples taken pre and post vaccination (P1060715H07-P1060815H06). The PPSV23 pneumococcal vaccine was admistered inbetween timepoints at approximately 10.30am, prior to datapoint P1060715H11. Following the vaccination, and after the 24 hour monitoring, daily samples were taken for about a month (up to sample P1070715H08), to capture innate and adaptive responses in saliva. Two more weekly samples followed, with then monthly samples till the end of the investigation. Omics sample analysis includes: RNA-sequencing of total RNA, small RNA sequencing in saliva extracellular vesicles and saliva mass spectrometry proteomics. Note on sample naming: The sample identifier/name P1MMDDYYHhh corresponds to: patient index:P1, date MMDDYY and hour hh preceded by H using 24 hour enumeration.
2020-01-31 | GSE108664 | GEO
Project description:The investigation includes findings from our clinical trial, monitoring individualized response to pneumococcal vaccination, where we have carried out integrative profiling assessment of saliva pre and post vaccination in a single individual. This is to our knowledge the most extensive saliva-centered omics dataset on an individual, covering 100 timepoints over the course of one year. The time span covers a healthy period as well as comprehensive monitoring of innate and adaptive immune responses following pneumococcal vaccination. Protein and RNA from saliva were produced at each timepoint (100 timepoints), and mass spectrometry proteomics and RNA-sequencing were carried out for all samples in non-targeted comprehensive profiling. Specifically, a single individual (male, 38) was profiled over multiple timepoints during healthy periods, as well as post treatment with pneumococcal vaccine (PPSV23). Initially pre-immunization samples, including a 24 hour period with hourly sampling (samples P1052515H07-P1052615H08), were collected to provide a comparative baseline. A subsequent 24-hour time course was performed, with again hourly samples taken pre and post vaccination (P1060715H07-P1060815H06). The PPSV23 pneumococcal vaccine was admistered inbetween timepoints at approximately 10.30am, prior to datapoint P1060715H11. Following the vaccination, and after the 24 hour monitoring, daily samples were taken for about a month (up to sample P1070715H08), to capture innate and adaptive responses in saliva. Two more weekly samples followed, with then monthly sample till the end of the investigation. Omics sample analysis includes: RNA-sequencing of total RNA, small RNA sequencing in saliva extracellular vesicles and saliva mass spectrometry proteomics. Note on sample naming: The sample identifier/name P1MMDDYYHhh corresponds to: patient index:P1, date MMDDYY and hour hh preceded by H using 24 hour enumeration.
2020-01-31 | GSE108666 | GEO
Project description:The investigation includes findings from our clinical trial, monitoring individualized response to pneumococcal vaccination, where we have carried out integrative profiling on peripheral blood mononuclear cells (PBMCs) and saliva pre and post vaccination in a single individual. This is to our knowledge the most extensive saliva-centered omics dataset on an individual, covering 100 timepoints over the course of one year. The time span covers a healthy period as well as comprehensive monitoring of innate and adaptive immune responses following pneumococcal vaccination. Protein and RNA from saliva and PBMCs were produced at each timepoint (100 timepoints for saliva, 25 for PBMCs), and mass spectrometry proteomics and RNA-sequencing were carried out for all samples in non-targeted comprehensive profiling. Specifically, a single individual (male, 38) was profiled over multiple timepoints during healthy periods, as well as post treatment with pneumococcal vaccine (PPSV23). Initially pre-immunization samples, including a 24 hour period with hourly sampling (samples P1052515H07-P1052615H08), were collected to provide a comparative baseline. A subsequent 24-hour time course was performed, with again hourly samples taken pre and post vaccination (P1060715H07-P1060815H06). The PPSV23 pneumococcal vaccine was admistered inbetween timepoints at approximately 10.30am, prior to datapoint P1060715H11. Following the vaccination, and after the 24 hour monitoring, daily samples were taken for about a month (up to sample P1070715H08), to capture innate and adaptive responses in saliva. Two more weekly samples followed, with then monthly sample till the end of the investigation. Concurrently, weekly or monthly PBMC samples were taken. Omics sample analysis includes: RNA-sequencing of total RNA in saliva and PBMCs. small RNA sequencing in saliva. Proteomics in saliva and PBMCs. small RNA from extracellular vesicles in saliva. Note on sample naming: The sample identifier/name P1MMDDYYHhh corresponds to: patient index:P1, date MMDDYY and hour hh preceded by H using 24hour enumeration. Overall the study produced 100 timepoints for saliva in the span of a year, as well as 30 PBMC samples.
2020-01-31 | GSE108665 | GEO
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:Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination, and 7, 21, and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.
2016-12-26 | GSE92884 | GEO
Project description:"The investigation includes findings from our clinical trial, monitoring individualized response to pneumococcal vaccination, where we have carried out integrative profiling on peripheral blood mononuclear cells (PBMCs) and saliva pre and post vaccination. This is to our knowledge the most extensive saliva-centered omics dataset on an individual, covering more than 100 timepoints over the course of one year. The time span covers a healthy period as well as comprehensive monitoring of innate and adaptive immune responses following pneumococcal vaccination. Protein and RNA from saliva and PBMCs were extracted at various timepoints (100+ timepoints for saliva, 25 for PBMCs), and mass spectrometry proteomics and RNA-sequencing were carried out for all samples in non-targeted comprehensive profiling.
Specifically, a single individual was profiled over multiple timepoints during healthy periods, as well as post treatment with pneumococcal vaccine (PPSV23). Initially pre-immunization samples, including a 24 hour period with hourly sampling (samples P1052515H07-P1052615H08), were collected to provide a comparative baseline. A subsequent 24-hour time course was performed, with again hourly samples taken pre and post vaccination (P1060715H07-P1060815H06). The PPSV23 pneumococcal vaccine was admistered inbetween timepoints at approximately 10.30am, prior to datapoint P1060715H11. Following the vaccination, and after the 24 hour monitoring, daily samples were taken for about a month (up to sample P1070715H08), to capture innate and adaptive responses in saliva. Two more weekly samples followed, with then monthly sample till the end of the investigation. Concurrently, weekly or monthly PBMC samples were taken.
Omics sample analysis includes: RNA-sequencing of total RNA in saliva and PBMCs. small RNA sequencing in saliva. Proteomics in saliva and PBMCs. For the Proteomics, samples were ran in sets of 6 (5 timepoints + common reference from pooled sample sets), using Tandem Mass Tagged (TMT labeling, 6-plex).
Note on sample naming: The sample identifier/name P1MMDDYYHhh corresponds to: patient index:P1, date MMDDYY and hour hh preceded by H using 24hour enumeration, based on EST times.
2017-12-28 | MSV000081869 | MassIVE
Project description:Purpose: Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. Methods: In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Results: Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. Conclusions: These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.
2021-03-10 | GSE164649 | GEO
Project description:Patients with inflammatory bowel disease (IBD) will be assessed for immunologic response to pneumococcal vaccination. Patients with IBD meet criteria as outlined by the Centers for Disease Control (CDC) for pneumococcal vaccination, yet the investigators have found that pneumococcal vaccination in this population is under-utilized. It is unknown whether or not IBD or IBD-related medications impact the immune response to this recommended vaccine.
Three groups of 25 patients each will be recruited. The first group will consist of outpatients with IBD who are receiving infliximab (Remicade TM) while on concommitant immunosuppressive therapy (with either 6MP, azathioprine, or methotrexate). This group is intended to represent a common ‘heavily immunosuppressed’ patient group with IBD.
The second group will consist of patients with IBD seen in our outpatient clinic who are not on any immune-suppressive medications. These patients meet CDC criteria for vaccination by virtue of having a chronic medical illness. The third group will consist of healthy age-matched (to the first group) controls.
After obtaining informed consent, patients will be screened with baseline lab tests including testing for antibodies against pneumococcus. At the baseline visit, patients will also undergo a brief medical history, physical examination, and assessment of their IBD disease activity.
Included patients will then undergo a one-time intramuscular vaccination with 23-valent polysaccharide pneumococcal vaccine (Pneumovax TM). One month later, subjects will return for a blood draw to assess for response to pneumococcal vaccination.
| 2066877 | ecrin-mdr-crc
Project description:The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle.
2018-07-24 | GSE117525 | GEO