Evaluation of Dendrimer-Like Alpha-D-Glucan Nanoparticles as a Vaccine Adjuvant
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 evaluated the potential of dendrimer-like α-D-glucan nanoparticles, derived from a variety of sweet corn, as a vaccine adjuvant. The nanoparticles, termed Nano-11, have an average diameter of 75-80 nm and were modified to give them a positive surface charge. Injection of antigens with Nano-11 significantly increased the amount of antigen-specific antibodies in the serum. Nano-11 increased the uptake of antigens, costimulatory expression and secretion of IL-1β by dendritic cells in vitro. LDH assay revealed that Nano-11 caused a low level of cytotoxicity to dendritic cells in vitro. In vivo imaging of fluorescently-labeled Nano-11 injected intramuscularly demonstrated that the nanoparticles were retained at the injection site and gradually cleared over the course of three weeks. Nano-11 caused a mild transient inflammatory response at the injection site with monocytes and macrophages being the most abundant cells and relatively few neutrophils. Nano-11 enhanced the delivery of antigen to antigen-presenting cells on a per cell basis and preferentially targets the antigen to migratory dendritic cells that travel to the draining lymph node. In vitro assays demonstrated that Nano-11 was taken up by dendritic cells through multiple phagocytosis and endocytosis mechanisms and was shifted to lysosomes within one hour after uptake. These results demonstrate that Nano-11 is an effective next generation vaccine adjuvant.
Degree
Ph.D.
Advisors
HogenEsch, Purdue University.
Subject Area
Immunology
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