title: Antigen delivery via hydrophilic PEG-b-PAGE-b-PLGA nanoparticles boosts vaccination induced T cell immunity.
abstract: Here, we evaluate the use of hydrophilic PEG-b-PAGE-b-PLGA (PPP) for the preparation of antigen loaded nanoparticles (NPs) as a platform for prophylactic vaccination. To investigate the suitability of PPP-NPs for antigen delivery, we used the double emulsion evaporation technique to prepare NPs of different sizes, antigen-loading efficiencies and -release kinetics for the model antigen Ovalbumin (OVA). Prior to applying the PPP-NPs in biological in vitro or in vivo models, all materials were tested for absence of cytotoxicity and endotoxins. While the uptake of NPs in antigen presenting cells was size but not polymer dependent, the efficiency of cross presentation of NP-associated antigen on MHC I molecules for CD8 T cell activation depended on the polymer type. T cell activation by antigen-presenting cells was significantly increased in vitro if antigen was delivered via PPP NPs compared to PLGA NPs or soluble OVA, although antigen content was the same in all tested formulations. Subcutaneous application of PPP-OVA-NPs even without adjuvants led to generation of potent CD8 T cell-mediated OVA-specific cytotoxicity in vivo that was more pronounced than after application of OVA alone or PLGA-OVA-NPs. Our data suggest that PPP-NPs can serve as platform for antigen-delivery in future vaccination formulations. Although PPP-NPs already bear intrinsic adjuvant-function, the complementation with TLR ligands loaded inside NPs may further strengthen the immune response to a point, where it might be possible to use it as a therapeutic vaccine to break immune tolerance in chronic disease states.
authors.affiliation: Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Rietscher
authors.affiliation: BioMed X Innovation Center, Heidelberg, Germany; Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schröder
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Kiel, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Janke
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller University, Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich-Schiller University, Jena, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Czaplewska
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller University, Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich-Schiller University, Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gottschaldt
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Kiel, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Scherließ
authors.affiliation: Merck Serono, Darmstadt, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hanefeld
authors.affiliation: Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich-Schiller University, Jena, Germany; Jena Center for Soft Matter (JCSM), Friedrich-Schiller University, Jena, Germany.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Institute of Molecular Immunology, Technische Universität München, Munich, Germany.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
authors.affiliation: Department of Drug Delivery (DDEL), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany; Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany. Electronic address: claus-michael.lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000737:chemistry* / Q000276:immunology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D014612:Vaccines; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D010047:Ovalbumin
keywords: Cellular uptake; Nanomedicines; Poly(allyl glycidyl ether); Poly(d,l-lactide-co-glycolide); Polyethylene glycol; Vaccination