title: Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine: In vivo tracking and evaluation of antigen-specific CD8(+) T cell immune response.
abstract: Particulate antigen delivery systems aimed at the induction of antigen-specific T cells form a promising approach in immunotherapy to replace pharmacokinetically unfavorable soluble antigen formulations. In this study, we developed a delivery system using the model protein antigen ovalbumin (OVA) encapsulated in nanoparticles based on the hydrophilic polyester poly(lactide-co-hydroxymethylglycolic acid) (pLHMGA). Spherical nanoparticles with size 300-400 nm were prepared and characterized and showed a strong ability to deliver antigen to dendritic cells for cross-presentation to antigen-specific T cells in vitro. Using near-infrared (NIR) fluorescent dyes covalently linked to both the nanoparticle and the encapsulated OVA antigen, we tracked the fate of this formulation in mice. We observed that the antigen and the nanoparticles are efficiently co-transported from the injection site to the draining lymph nodes, in a more gradual and durable manner than soluble OVA protein. OVA-loaded pLHMGA nanoparticles efficiently induced antigen cross-presentation to OVA-specific CD8+ T cells in the lymph nodes, superior to soluble OVA vaccination. Together, these data show the potential of pLHMGA nanoparticles as attractive antigen delivery vehicles.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sima
authors.initials: S
authors.lastname: Rahimian
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Kleinovink
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke F
authors.initials: MF
authors.lastname: Fransen
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Mezzanotte
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Henrik
authors.initials: H
authors.lastname: Gold
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wisse
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Hermen
authors.initials: H
authors.lastname: Overkleeft
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Amidi
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Clemens W
authors.initials: CW
authors.lastname: Löwik
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: F.A.Ossendorp@lumc.nl.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. Electronic address: W.E.Hennink@uu.nl.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D003713:Dendritic Cells / Q000378:metabolism; D000939:Epitopes; D057927:Hydrophobic and Hydrophilic Interactions; D007109:Immunity; D007259:Infrared Rays; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010047:Ovalbumin / Q000737:chemistry*; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D013194:Staining and Labeling; D014612:Vaccines / Q000276:immunology*
chemical_list: D000939:Epitopes; D011091:Polyesters; D014612:Vaccines; C576815:poly(lactide-co-hydroxymethyl glycolide); D010047:Ovalbumin
keywords: Antigen delivery; In vivo tracking; Nanoparticles; Near-infrared imaging; pLHMGA