A New RNA-Based Adjuvant Enhances Virus-Specific Vaccine Responses by Locally Triggering TLR- and RLH-Dependent Effects.
Annett ZieglerClaudia SoldnerStefan LienenklausJulia SpanierStephanie TrittelPeggy RieseThomas KrampsSiegfried WeissRegina HeidenreichEdith JasnyCarlos A GuzmánKarl-Josef KallenMariola Fotin-MleczekUlrich KalinkePublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
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.
Keyphrases
- toll like receptor
- immune response
- dendritic cells
- inflammatory response
- early stage
- high fat diet induced
- high glucose
- diabetic rats
- nuclear factor
- drug induced
- squamous cell carcinoma
- clinical trial
- open label
- oxidative stress
- insulin resistance
- disease virus
- high intensity
- dengue virus
- protein kinase
- zika virus
- placebo controlled