Journal article
Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans
The Journal of experimental medicine, v 208(12), pp 2357-2366
21 Nov 2011
PMID: 22065672
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
As shown by transcriptional analysis of blood samples from human volunteers, injection with synthetic dsRNA (an agonist of the TLR3 and MDA5 pattern recognition receptors) triggered up-regulation of genes involved in innate immune pathways, similar to those induced by vaccination with the efficacious yellow fever vaccine.
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.
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Details
- Title
- Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans
- Creators
- Marina Caskey - Rockefeller UniversityFrançois Lefebvre - Centre Hospitalier de l’Université de MontréalAbdelali Filali-Mouhim - Centre Hospitalier de l’Université de MontréalMark J. Cameron - Vaccine & Gene Therapy Institute of FloridaJean-Philippe Goulet - Centre Hospitalier de l’Université de MontréalElias K. Haddad - andGaëlle Breton - Rockefeller UniversityChristine Trumpfheller - Rockefeller UniversitySarah Pollak - Rockefeller UniversityIrina Shimeliovich - Rockefeller UniversityAngela Duque-Alarcon - Vaccine & Gene Therapy Institute of FloridaLi Pan - Vaccine & Gene Therapy Institute of FloridaAnnette Nelkenbaum - Rockefeller UniversityAndres M. Salazar - Oncovir (United States)Sarah J. Schlesinger - Rockefeller UniversityRalph M. Steinman - Rockefeller UniversityRafick P. Sékaly - Centre Hospitalier de l’Université de Montréal
- Publication Details
- The Journal of experimental medicine, v 208(12), pp 2357-2366
- Publisher
- The Rockefeller University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Web of Science ID
- WOS:000297870700005
- Scopus ID
- 2-s2.0-84855486511
- Other Identifier
- 991020100082704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental