title: Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
abstract: 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 up-regulation of genes involved in multiple innate immune pathways in all subjects, including interferon (IFN) and inflammasome signaling. Blocking type I IFN receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate immune pathways were similarly induced in volunteers immunized with the highly efficacious yellow fever vaccine. Therefore, a chemically defined PRR agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immune responses in humans.
authors: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10065, USA.
authors: Marina
authors: M
authors: Caskey
authors: François
authors: F
authors: Lefebvre
authors: Abdelali
authors: A
authors: Filali-Mouhim
authors: Mark J
authors: MJ
authors: Cameron
authors: Jean-Philippe
authors: JP
authors: Goulet
authors: Elias K
authors: EK
authors: Haddad
authors: Gaëlle
authors: G
authors: Breton
authors: Christine
authors: C
authors: Trumpfheller
authors: Sarah
authors: S
authors: Pollak
authors: Irina
authors: I
authors: Shimeliovich
authors: Angela
authors: A
authors: Duque-Alarcon
authors: Li
authors: L
authors: Pan
authors: Annette
authors: A
authors: Nelkenbaum
authors: Andres M
authors: AM
authors: Salazar
authors: Sarah J
authors: SJ
authors: Schlesinger
authors: Ralph M
authors: RM
authors: Steinman
authors: Rafick P
authors: RP
authors: Sékaly
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D058847:Inflammasomes / Q000378:metabolism; D007279:Injections, Subcutaneous; D007372:Interferons / Q000378:metabolism; D046228:Microarray Analysis; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D058847:Inflammasomes; D014765:Viral Vaccines; D011107:Polylysine; C019531:poly ICLC; D007372:Interferons; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C