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GSE32862
Homo sapiens
119 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
Adjuvants 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.
Publication Title
Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
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Time
View Samples- Homo sapiens
- 142 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Correlates 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.
Publication Title
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.
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