A New RNA-Based Adjuvant Enhances Virus-Specific Vaccine Responses by Locally Triggering TLR- and RLH-Dependent Effects
| Autor: | Edith Jasny, Claudia Soldner, Annett Ziegler, Regina Heidenreich, Thomas Kramps, Karl-Josef Kallen, Peggy Riese, Stephanie Trittel, Ulrich Kalinke, Stefan Lienenklaus, Mariola Fotin-Mleczek, Julia Spanier, Carlos A. Guzmán, Siegfried Weiss |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
RNA Untranslated medicine.medical_treatment Protein subunit Immunology Biology Antibodies Viral Virus Mice 03 medical and health sciences 0302 clinical medicine Adjuvants Immunologic Viral Envelope Proteins medicine Animals Immunology and Allergy Vaccines Virus-Like Particle Mice Inbred BALB C Membrane Glycoproteins Vaccination TLR7 Th1 Cells biology.organism_classification Virology 030104 developmental biology Toll-Like Receptor 7 Influenza Vaccines Vesicular stomatitis virus Immunoglobulin G Myeloid Differentiation Factor 88 Vaccines Subunit TLR3 biology.protein DEAD Box Protein 58 Antibody Adjuvant 030215 immunology |
| Zdroj: | The Journal of Immunology. 198:1595-1605 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Among innovative adjuvants conferring a Th1-shift, RNAdjuvant is a promising candidate. This adjuvant consists of a 547-nt uncapped noncoding ssRNA containing polyU repeats that is stabilized by a cationic carrier peptide. Whereas vaccination of mice with an influenza subunit vaccine induced moderate virus-specific IgG1, vaccination together with RNAdjuvant significantly enhanced this IgG1 and additionally promoted the formation of IgG2b/c, which is indicative of Th1 responses. Furthermore, such sera neutralized influenza virus, whereas this effect was not detected upon vaccination with the subunit vaccine alone. Similarly, upon vaccination with virus-like particles displaying vesicular stomatitis virus G protein, RNAdjuvant promoted the formation of virus-specific IgG2b/c and enhanced neutralizing IgG responses to an extent that mice were protected against lethal virus infection. RNAdjuvant induced dendritic cells to upregulate activation markers and produce IFN-I. Although these effects were strictly TLR7 dependent, RNAdjuvant-mediated augmentation of vaccine responses needed concurrent TLR and RIG-I–like helicase signaling. This was indicated by the absence of the adjuvant effect in vaccinated MyD88−/−Cardif−/− mice, which are devoid of TLR (with the exception of TLR3) and RIG-I–like helicase signaling, whereas in vaccinated MyD88−/− mice the adjuvant effect was reduced. Notably, i.m. RNAdjuvant injection induced local IFN-I responses and did not induce systemic effects, implying good tolerability and a favorable safety profile for RNAdjuvant. |
| Databáze: | OpenAIRE |
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