title: A Generic Polymer-Protein Ligation Strategy for Vaccine Delivery.
abstract: Although the field of cancer immunotherapy is intensively investigated, there is still a need for generic strategies that allow easy, mild and efficient formulation of vaccine antigens. Here we report on a generic polymer-protein ligation strategy to formulate protein antigens into reversible polymeric conjugates for enhanced uptake by dendritic cells and presentation to CD8 T-cells. A N-hydroxypropylmethacrylamide (HPMA)-based copolymer was synthesized via RAFT polymerization followed by introduction of pyridyldisulfide moieties. To enhance ligation efficiency to ovalbumin, which is used as a model protein antigen, protected thiols were introduced onto lysine residues and deprotected in situ in the presence of the polymer. The ligation efficiency was compared for both the thiol-modified versus unmodified ovalbumin, and the reversibility was confirmed. Furthermore, the obtained nanoconjugates were tested in vitro for their interaction and association with dendritic cells, showing enhanced cellular uptake and antigen cross-presentation to CD8 T-cells.
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Lybaert
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Nane
authors.initials: N
authors.lastname: Vanparijs
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Ghent Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: Fierens
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Ghent Belgium.
authors.forename: Martijn
authors.initials: M
authors.lastname: Schuijs
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Lutz
authors.initials: L
authors.lastname: Nuhn
authors.affiliation: VIB Inflammation Research Center, Ghent University , Technologiepark 927, 9052 Ghent Belgium.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Department of Pharmaceutics, Ghent University , Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D058726:Nanoconjugates / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry* / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry* / Q000276:immunology
chemical_list: D000941:Antigens; D008689:Methacrylates; D058726:Nanoconjugates; D018074:Vaccines, Conjugate; D010047:Ovalbumin; C032802:hydroxypropyl methacrylate