title: Assessment of the enhancement of PLGA nanoparticle uptake by dendritic cells through the addition of natural receptor ligands and monoclonal antibody.
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.
authors.affiliation: Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone KT15 3NB, United Kingdom; Department of Microbial & Cellular Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. Electronic address: adam.walters@ndm.ox.ac.uk.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Walters
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: s.somavarapu@ucl.ac.uk.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.affiliation: Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone KT15 3NB, United Kingdom; Department of Microbial & Cellular Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. Electronic address: v.riitho@cgiar.org.
authors.forename: Victor
authors.initials: V
authors.lastname: Riitho
authors.affiliation: Department of Microbial & Cellular Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom. Electronic address: g.stewart@surrey.ac.uk.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Stewart
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, United Kingdom. Electronic address: bryan.charleston@pirbright.ac.uk.
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
authors.affiliation: Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone KT15 3NB, United Kingdom; School of Veterinary Medicine, University of Surrey, Guildford GU2 7XH, United Kingdom. Electronic address: falko.steinbach@apha.gsi.gov.uk.
authors.forename: Falko
authors.initials: F
authors.lastname: Steinbach
authors.affiliation: Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone KT15 3NB, United Kingdom. Electronic address: simon.graham@pirbright.ac.uk.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Graham
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D019344:Lactic Acid; D037181:Lectins, C-Type / Q000276:immunology*; D008024:Ligands; D008351:Mannans / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface / Q000276:immunology*; D014612:Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D008024:Ligands; D008351:Mannans; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan
keywords: Cattle; DEC-205 antibody; Dendritic cell; Mannose; Nanoparticle; Targeting