title: Cutting Edge: The RIG-I Ligand 3pRNA Potently Improves CTL Cross-Priming and Facilitates Antiviral Vaccination.
abstract: Protective immunity against intracellular pathogens involves the induction of robust CTL responses. Vaccination with protein Ags establishes such responses only when combined with immune-stimulatory adjuvants. In this study, we compared different adjuvants and identified triphosphate RNA (3pRNA) as especially effective at inducing CTL responses. 3pRNA sensing required IPS-1/MAVS signaling and induced type I IFN in plasmacytoid dendritic cells and macrophages, with the latter being more important for the adjuvant effect. Type I IFN acted on CD11c(+) cells, especially on CD8α(+) Batf3-dependent dendritic cells. Vaccination with OVA in combination with 3pRNA protected mice from a subsequent OVA-encoding adenovirus infection in a CD8(+) cell-dependent manner and more efficiently than other adjuvants. In summary, 3pRNA is a superior adjuvant for CTL activation and might be useful to facilitate antiviral immunization strategies.
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms University, Bonn 53105, Germany; khochhei@gmail.com ckurts@web.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hochheiser
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms University, Bonn 53105, Germany;
authors.forename: Marika
authors.identifier: http://orcid.org/0000-0001-9006-6879
authors.initials: M
authors.lastname: Klein
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms University, Bonn 53105, Germany;
authors.forename: Catherine
authors.initials: C
authors.lastname: Gottschalk
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms University, Bonn 53105, Germany;
authors.forename: Florian
authors.identifier: http://orcid.org/0000-0002-9231-5848
authors.initials: F
authors.lastname: Hoss
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, Düsseldorf 40225, Germany; and.
authors.forename: Stefanie
authors.identifier: http://orcid.org/0000-0002-9707-8191
authors.initials: S
authors.lastname: Scheu
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, Bonn 53127, Germany.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0002-0815-6750
authors.initials: C
authors.lastname: Coch
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, Bonn 53127, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.affiliation: Institute of Experimental Immunology, Rheinische Friedrich-Wilhelms University, Bonn 53105, Germany; khochhei@gmail.com ckurts@web.de.
authors.forename: Christian
authors.identifier: http://orcid.org/0000-0002-6620-2401
authors.initials: C
authors.lastname: Kurts
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D045142:Cross-Priming / Q000276:immunology*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008024:Ligands; D051379:Mice; D012313:RNA / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D008024:Ligands; D012313:RNA; D014765:Viral Vaccines; C512612:MAVS protein, mouse; C503356:Ddx58 protein, mouse