Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

Détails

Ressource 1Télécharger: BIB_0168D55523C9.P001.pdf (787.83 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_0168D55523C9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release
Périodique
Nanomaterials
Auteur(s)
Poecheim J., Heuking S., Brunner L., Barnier-Quer C., Collin N., Borchard G.
ISSN
2079-4991
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
5
Numéro
4
Pages
2317-1334
Langue
anglais
Résumé
Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.
Mots-clé
adjuvants, toll-like receptor, NOD-like receptor, cationic nanoparticles, DNA vaccine, muramyl dipeptide
Web of science
Open Access
Oui
Création de la notice
28/01/2016 15:29
Dernière modification de la notice
20/08/2019 13:23
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