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

Abstract

Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like α-D-glucan nanoparticles with a diameter of 70–80 nm. 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.

Adjuvants: Discovering the next generation of vaccine boosters

A plant-derived nanoparticle boosts the immune system’s response to foreign stimuli, such as vaccines, through newly discovered mechanisms. Harm HogenEsch and his team from Purdue University, USA, previously discovered that their formulated nanoparticle adjuvant, Nano-11, increased immune responses to stimuli in mice. Adjuvants are formulations often co-administered with vaccines to promote interaction with the host’s immune system, conferring greater protection. In this study, the scientists found that Nano-11 functions by inducing a temporary inflammation, attracting immune cells to the injection site. The nanoparticles also facilitate the transport of the stimuli to the lymph nodes. Nano-11 is metabolized without deposition in any major internal organs, suggesting a positive safety profile. As current aluminum-based adjuvants are sometimes poorly effective and can cause local adverse reactions, nanoparticle-based potentiators such as Nano-11 may form the next generation of adjuvants.