We tested the effects of co-infection on vaccine response to YFV-17D.
Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.
Specimen part
View SamplesAdjuvants are critical for the success of vaccines, and agonists for microbial pattern recognition receptors are promising new candidates. A mechanism for the immune enhancing role of adjuvants is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double stranded RNA (poly ICLC), a ligand for TLR3 and MDA-5 cytosolic RNA helicase. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC showed upregulation of genes involved in multiple innate immune pathways in all subjects, including interferon and inflammasome signaling. Blocking of type I interferon receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate pathways were similarly induced in volunteers immunized with the highly efficacious Yellow Fever Vaccine. Therefore a chemically defined microbial agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immunity, here for a live attenuated viral vaccine in humans.
Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
Time
View SamplesCorrelates of immune mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of forty volunteers followed for up to one year after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity including complement, the inflammasome and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (Modular IMmune In vitro Construct (MIMIC) system), by the coordinated up-regulation of transcripts for specific transcription factors including STAT1, IRF7 and ETS2 that are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of masters transcription factors, that lead to the development of a broad, polyfunctional and persistent immune response that integrates all effector cells of the immune system.
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.
No sample metadata fields
View SamplesLaser capture microdissection coupled with microarray genes expression analysis were utilized in order to elucidate the regulatory networks active in epithelial cells of the neonatal and adult mouse uterus.
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Specimen part
View SamplesTo identify genes differentially expressed in the glandless uterus, whole uteri were collected from control (uterine glands present) and PUGKO (no uterine glands) mice at day of pseudopregnancy (DOPP) 3.5 (day DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the glandless uteri of PUGKO mice as compared to control mice.
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Specimen part
View SamplesTo identify candidate genes regulated by forkhead transcription factor box A2 (FOXA2) in the uterus, control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus.
Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus.
Specimen part
View SamplesDouble-stranded RNA (dsRNA) can enter different pathways in mammalian cells, including sequence-specific RNA interference, sequence-independent interferon response and editing by adenosine deaminases. To assess the potential of expressed dsRNA to induce interferon stimulated genes in somatic cells, we performed microarray analysis of HEK293 and HeLa cells transfected with a MosIR plasmid expressing an mRNA with a long inverted repeat structure in its 3UTR (MosIR) or with a parental MosIR plasmid (without inverted repeat) as a control.
dsRNA expression in the mouse elicits RNAi in oocytes and low adenosine deamination in somatic cells.
Specimen part
View SamplesWe performed a whole-transcriptome analysis of the peripheral blood of untreated patients with stage 1 PD (HoehnYahr scale).
Involvement of endocytosis and alternative splicing in the formation of the pathological process in the early stages of Parkinson's disease.
Specimen part, Disease
View SamplesWe have developed a method to generate muscle stem cells from pluripotent stem cells via teratoma formation. The goal of this study is to compare the transcriptome of a7+ VCAM+ myogenic cells derived from pluripotent stem cells versus satellite cells Overall design: RNA from a7+ VCAM+ myogenic cells derived from teratoma, transplanted muscles, E14.5 mouse embryos, and hindlimbs of 8-week-old mice. In 3 biological replicates
Skeletal Muscle Stem Cells from PSC-Derived Teratomas Have Functional Regenerative Capacity.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling.
Sex
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