title: PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation.
abstract: Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) represent a new approach for vaccine delivery due to their ability to be taken up by phagocytes and to activate immune responses. In the present study PLGA NPs were surface-modified with a TNFα mimicking peptide, and encapsulated soluble Leishmania antigens (sLiAg) and MPLA adjuvant. The synthesized PLGA NPs exhibited low cytotoxicity levels, while surface-modified NPs were more efficiently taken up by dendritic cells (DCs). The prepared nanoformulations induced maturation and functional differentiation of DCs by elevating co-stimulatory molecule levels and stimulating IL-12 and IL-10 production. Sensitized DCs promoted T cell priming, characterized by the development of mixed T cell subsets differentiation expressing Th lineage-specific transcriptional factors and cytokine genes. Moreover, PLGA NPs were biocompatible, while they were located in lymphoid organs and taken up by phagocytic cells. Our results suggest that surface-modified PLGA NPs encapsulating sLiAg and MPLA could be considered as an effective vaccine candidate against leishmaniasis.
authors.affiliation: Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias av., 11521 Athens, Greece; Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece.
authors.forename: Maritsa
authors.initials: M
authors.lastname: Margaroni
authors.affiliation: Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias av., 11521 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Agallou
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece; Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kontonikola
authors.affiliation: Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Karidi
authors.affiliation: Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Kammona
authors.affiliation: Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, 54124 Thessaloniki, Greece; Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
authors.forename: Costas
authors.initials: C
authors.lastname: Kiparissides
authors.affiliation: Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaitanaki
authors.affiliation: Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias av., 11521 Athens, Greece. Electronic address: ekaragouni@pasteur.gr.
authors.forename: Evdokia
authors.initials: E
authors.lastname: Karagouni
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D007891:Leishmania / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cytokine expression; Dendritic cells; Leishmania; Maturation; PLGA NPs; T cell priming