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Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells

Lu, F;Mosley, YC;Rosales, RJ;Carmichael, BE;Elesela, S;Yao, Y;HogenEsch, H;

Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like -D-glucan nanoparticles with a diameter of 7080nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant. Utilizing an in vivo imaging system, Nano-11 was shown to remain at the injection site after administration and cleared gradually over the course of 3 weeks. Injection of Nano-11 induced a transient inflammatory response characterized by recruitment of a mixed population of inflammatory cells, predominantly monocytes and macrophages with relatively few neutrophils. Recruited Mac-2+macrophages efficiently phagocytized the majority of Nano-11 at the injection site. Fluorescently labeled Nano-11 was present in cells in the draining lymph nodes 1 day after injection, with the majority contained in migratory dendritic cells. Injection of ovalbumin adsorbed to Nano-11 resulted in an increase of ovalbumin-containing cells in draining lymph nodes. Nano-11 delivered more antigen to antigen-presenting cells on a per cell basis and demonstrated more specific targeting to highly immunopotentiating migratory dendritic cells compared with soluble or aluminum hydroxide adsorbed ovalbumin. These results support the efficacy of Nano-11 and its potential use as a next generation vaccine adjuvant.