title: Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations.
abstract: The function of N-trimethyl chitosan (TMC) in dermal immunisation is unknown. Therefore we investigated the immunogenicity of both antigen-containing TMC nanoparticles and TMC/antigen solutions after intradermal injection. Nanoparticles were prepared with a size around 200 nm and a positive zetapotential. In vitro, TMC nanoparticles increased the uptake of OVA by dendritic cells (DCs) and both nanoparticles and TMC/OVA mixtures were able to induce upregulation of MHC-II, CD83 and CD86. These activated DCs could induce a Th2 biased T cell proliferation. A solution of plain OVA did not induce DC maturation or T cell proliferation. In vivo, mice were injected thrice with TMC based formulations containing either OVA or diphtheria toxoid (DT), a more relevant antigen. All TMC-containing formulations were able to increase the IgG titres compared to unadjuvanted antigen and induced a Th2 biased immune response. When using DT-containing TMC formulations, IgG titres and neutralising antibody titres could match up to those obtained after subcutaneous injection of DT-Alum. In conclusion, both soluble TMC/antigen mixtures and TMC nanoparticles are able to induce DC maturation and enhance immune responses after intradermal injection. This demonstrates that TMC functions as an immune potentiator for antigens delivered via the skin.
authors.affiliation: Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Bal
authors.forename: Bram
authors.initials: B
authors.lastname: Slütter
authors.forename: Elly
authors.initials: E
authors.lastname: van Riet
authors.forename: Annelieke C
authors.initials: AC
authors.lastname: Kruithof
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ding
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology; D012996:Solutions; D013499:Surface Properties; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014709:Vero Cells
chemical_list: D057134:Antibodies, Neutralizing; D000941:Antigens; D004168:Diphtheria Toxoid; D004337:Drug Carriers; D007074:Immunoglobulin G; C118071:N-trimethyl chitosan chloride; D012996:Solutions; D010047:Ovalbumin; D048271:Chitosan