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J Immunol. 2017 Feb 15;198(4):1595-1605. doi: 10.4049/jimmunol.1601129. Epub 2017 Jan 11.

A New RNA-Based Adjuvant Enhances Virus-Specific Vaccine Responses by Locally Triggering TLR- and RLH-Dependent Effects.

Author information

1
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, D-30625 Hannover, Germany.
2
Department of Molecular Immunology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
3
Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, D-30625 Hannover, Germany.
4
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany; and.
5
CureVac AG, D-72076 Tübingen, Germany.
6
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, D-30625 Hannover, Germany; ulrich.kalinke@twincore.de.

Abstract

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.

PMID:
28077601
DOI:
10.4049/jimmunol.1601129
[Indexed for MEDLINE]
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