Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants

Fangjia Lu, Alejandra Mencia, Lin Bi, Aaron Taylor, Yuan Yao, Harm HogenEsch

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The use of nanoparticles for delivery of vaccine antigens and as vaccine adjuvants is appealing because their size allows efficient uptake by dendritic cells and their biological properties can be tailored to the desired function. Here, we report the effect of chemically modified phytoglycogen, a dendrimer-like α-d-glucan nanoparticle, on dendritic cells in vitro, and the utility of this type of nanoparticle as a vaccine adjuvant in vivo. The modified phytoglycogen nanoparticle, termed Nano-11, has a positive surface charge which enabled electrostatic adsorption of negatively charged protein antigens. The Nano-11-antigen complexes were efficiently phagocytized by dendritic cells. Nano-11 induced increased expression of costimulatory molecules and the secretion of IL-1β and IL-12p40 by dendritic cells. Intramuscular injection of Nano-11-antigen formulations induced a significantly enhanced immune response to two different protein antigens. Examination of the injection site revealed numerous monocytes and relatively few neutrophils at one day after injection. The inflammation had nearly completely disappeared by 2 weeks after injection. These studies indicate that Nano-11 is an effective vaccine delivery vehicle that significantly enhances the immune response. This type of plant based nanoparticle is considered highly cost-effective compared with fully synthetic nanoparticles and appears to have an excellent safety profile making them an attractive adjuvant candidate for prophylactic vaccines.

Original languageEnglish (US)
Article number7587
Pages (from-to)51-59
Number of pages9
JournalJournal of Controlled Release
Volume204
DOIs
StatePublished - Apr 28 2015
Externally publishedYes

Keywords

  • Adjuvants
  • Dendritic cells
  • IL-1β
  • Inflammation
  • Nanoparticles
  • Vaccines

ASJC Scopus subject areas

  • Pharmaceutical Science

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