Assessment of the enhancement of PLGA nanoparticle uptake by dendritic cells through the addition of natural receptor ligands and monoclonal antibody

• Published in: Vaccine 2015-11, Vol.33 (48), p.6588-6595
• Main Authors: Walters, Adam A, Somavarapu, Satyanarayana, Riitho, Victor, Stewart, Graham R, Charleston, Bryan, Steinbach, Falko, Graham, Simon P
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Monoclonal - immunology; Antigens; Antigens, CD - immunology; Atoms & subatomic particles; Cattle; Cells, Cultured; Chitosan - pharmacology; DEC-205 antibody; Dendritic cell; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Humans; Immunogenicity; Lactic Acid; Lectins, C-Type - immunology; Ligands; Mannans - pharmacology; Mannose; Microscopy; Minor Histocompatibility Antigens; Nanoparticle; Nanoparticles - chemistry; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; R&D; Receptors, Cell Surface - immunology; Research & development; Targeting; Vaccines; Vaccines - chemistry; Vaccines - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2015.10.093

Abstract Targeting of specific receptors on antigen-presenting cells is an appealing prospect in the production of novel nanoparticulate vaccines. In particular, the targeting of vaccines to dendritic cell (DC) subsets has been shown in models to significantly improve the induction of immune responses. This paper describes the evaluation of natural ligands, mannan and chitosan, and monoclonal antibodies as targeting motifs to enhance uptake of PLGA nanoparticle carriers by bovine DCs. To assess enhancement of uptake after the addition of natural ligands a bovine monocyte derived DC (MoDC) model was used. For the assessment of monoclonal antibody targeting, the model was expanded to include afferent lymph DCs (ALDCs) in a competitive uptake assay. Mannan, proved unsuccessful at enhancing uptake or targeting by MoDCs. Chitosan coated particle uptake could be impeded by the addition of mannan suggesting uptake may be mediated through sugar receptors. Inclusion of monoclonal antibodies specific for the DEC-205 (CD205) receptor increased the number of receptor expressing DCs associated with particles as well as the number of particles taken up by individual cells. These results support the further evaluation of active targeting of nanovaccines to DCs to enhance their immunogenicity in cattle and other large mammalian species including humans.