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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / adverse effects
  • Animals
  • Antibodies, Viral / blood
  • DEAD Box Protein 58 / immunology
  • DEAD Box Protein 58 / metabolism
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / metabolism
  • RNA, Untranslated / immunology*
  • Th1 Cells / immunology
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 7 / metabolism
  • Vaccination
  • Vaccines, Subunit / immunology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / immunology


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • G protein, vesicular stomatitis virus
  • Immunoglobulin G
  • Influenza Vaccines
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Untranslated
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Vaccines, Subunit
  • Vaccines, Virus-Like Particle
  • Viral Envelope Proteins
  • Ddx58 protein, mouse
  • DEAD Box Protein 58