title: Alginate-coated chitosan nanogels differentially modulate class-A and class-B CpG-ODN targeting of dendritic cells and intracellular delivery.
abstract: CpG-oligodeoxynucleotides (CpG-ODNs) interact with dendritic cells (DCs), but evidence is less clear for CpG-ODN admixed with or incorporated into vaccine delivery vehicles. We loaded alginate-coated chitosan-nanogels (Ng) with class-A or class-B CpG-ODN, and compared with the same CpG-ODNs free or admixed with empty Ng. Experiments were performed on both porcine and human blood DC subpopulations. Encapsulation of class-A CpG-ODN (loading into Ng) strongly reduced the CpG-ODN uptake and intracellular trafficking in the cytosol; this was associated with a marked deficiency in IFN-α induction. In contrast, encapsulation of class-B CpG-ODN increased its uptake and did not influence consistently intracellular trafficking into the nucleus. The choice of CpG-ODN class as adjuvant is thus critical in terms of how it will behave with nanoparticulate vaccine delivery vehicles. The latter can have distinctive modulatory influences on the CpG-ODN, which would require definition for different CpG-ODN and delivery vehicles prior to vaccine formulation.
  
  
  BACKGROUND
  This basic science study investigates the role of class-A and class-B CpG-oligodeoxynucleotides loaded into alginate-coated chitosan nanogels, demonstrating differential effects between the two classes as related to the use of these nanoformulations as vaccine delivery vehicles.
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland. Electronic address: thomas.demoulins@ivi.admin.ch.
authors.forename: Thomas
authors.initials: T
authors.lastname: Démoulins
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Milona
authors.affiliation: Institute of Virology and Immunology (IVI), Mittelhäusern, Switzerland.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: McCullough
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013552:Swine
chemical_list: D000464:Alginates; C408982:CPG-oligonucleotide; D006603:Hexuronic Acids; D009838:Oligodeoxyribonucleotides; D020723:Glucuronic Acid; D048271:Chitosan
keywords: Blood dendritic cell targeting; CpG-ODN; Intracellular delivery; Nanoparticles