Alginate-coated chitosan nanogel capacity to modulate the effect of TLR ligands on blood dendritic cells

Biodegradable nanoparticles have been employed for vaccine delivery, frequently admixed with adjuvants. Surprisingly, there is little information on their modulation of immune responses, speculated to be negligible. We analyzed the immunomodulatory capacity of alginate-coated chitosan nanogels (Ng), on porcine and human blood dendritic cells (DCs), when applied with defined adjuvants targeting different DC subpopulations. DC maturation, cytokine production and cell migration were assessed. Ng differentially influenced the immunomodulatory characteristics of individual Toll-like receptor (TLR) ligands: Pam3Cys-SK4-induced IL-1β was enhanced; CpG-oligodeoxynucleotides (CpG-ODN)-induced IFN-α, IL-6 and TNFα were impaired; CpG-ODN-induced CD86 and CCR7, and cell migration, were diminished—plasmacytoid DCs (pDCs) were particularly sensitive. Therein, the Ng influence on DC endocytosis of the TLR ligands was apparently a major contributory element. This demonstrates the importance of predefining the interplay between delivery vehicles and admixed immunostimulatory moieties, for ensuring appropriate immune activation and efficacious combinations.From the Clinical EditorBiodegradable nanoparticles have been utilized in vaccine delivery; however, there is little information available on their immunomodulatory properties, which are thought to be negligible. This study clearly demonstrates that nanogels do influence the developing immune response, which needs to be taken into consideration when utilizing these otherwise very efficacious vaccine delivery approaches.

Graphical AbstractWe wished to determine the role of biodegradable nanoparticles in immunomodulation when applied with defined adjuvants. We report that alginate-coated chitosan nanogels (Ng) do not themselves impact significantly on blood dendritic cells. In contrast, when admixed with free Pam3Cys-SK4 or type A CpG-ODN, a clear immunomodulatory influence was apparent. However, this immunomodulatory activity was dependent on the TLR ligand employed, and whether pDCs or cDCs were involved. From this, we are now aware that changing the adjuvant in a nanoparticle vaccine formulation may alter the characteristics of immune response induction beyond that envisaged for the TLR ligand alone.Figure optionsDownload high-quality image (216 K)Download as PowerPoint slide