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Synthetic Double-Stranded Rna Induces Innate Immune Responses Similar To A Live Viral Vaccine In Humans, Marina Caskey, François Lefebvre, Ali Filali-Mouhim
Synthetic Double-Stranded Rna Induces Innate Immune Responses Similar To A Live Viral Vaccine In Humans, Marina Caskey, François Lefebvre, Ali Filali-Mouhim
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Adjuvants are critical for the success of vaccines. Agonists of microbial pattern recognition receptors (PRRs) are promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double-stranded RNA (polyinosinic:polycytidylic acid [poly IC] stabilized with poly-l-lysine [poly ICLC]), an agonist for toll-like receptor (TLR) 3, and the cytosolic RNA helicase MDA-5. 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 (IFN) and inflammasome signaling. …