Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants.
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.
Department of Comparative Pathobiology, United States.
Fangjia
F
Lu
Department of Food Science, United States.
Alejandra
A
Mencia
Department of Food Science, United States.
Lin
L
Bi
Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, United States.
Aaron
A
Taylor
Department of Food Science, United States.
Yuan
Y
Yao
Department of Comparative Pathobiology, United States. Electronic address: hogenesch@purdue.edu.
Harm
H
HogenEsch
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005936:Glucans / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D020005:Propanols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013386:Succinates / Q000737:chemistry; D013499:Surface Properties
D000276:Adjuvants, Immunologic; D016207:Cytokines; D050091:Dendrimers; D005936:Glucans; D020005:Propanols; D000644:Quaternary Ammonium Compounds; D013386:Succinates; C028480:octenyl succinate; D010047:Ovalbumin; C496948:(3-chloro-2-hydroxypropyl)trimethylammonium chloride
Adjuvants; Dendritic cells; IL-1β; Inflammation; Nanoparticles; Vaccines