PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation

Maritsa Margaroni; Maria Agallou; Katerina Kontonikola; Konstantina Karidi; Olga Kammona; Costas Kiparissides; Catherine Gaitanaki; Evdokia Karagouni

doi:10.1016/j.ejpb.2016.05.018

PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation

Eur J Pharm Biopharm. 2016 Aug:105:18-31. doi: 10.1016/j.ejpb.2016.05.018. Epub 2016 May 25.

Authors

Maritsa Margaroni¹, Maria Agallou², Katerina Kontonikola³, Konstantina Karidi⁴, Olga Kammona⁴, Costas Kiparissides³, Catherine Gaitanaki⁵, Evdokia Karagouni⁶

Affiliations

¹ 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.
² Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias av., 11521 Athens, Greece.
³ 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.
⁴ Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, 57001 Thessaloniki, Greece.
⁵ Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece.
⁶ Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vas. Sofias av., 11521 Athens, Greece. Electronic address: ekaragouni@pasteur.gr.

PMID: 27235727
DOI: 10.1016/j.ejpb.2016.05.018

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.

Keywords: Cytokine expression; Dendritic cells; Leishmania; Maturation; PLGA NPs; T cell priming.

MeSH terms

Adjuvants, Immunologic / administration & dosage
Animals
Antigens, Protozoan / immunology*
Cell Differentiation*
Female
Lactic Acid / chemistry*
Leishmania / immunology*
Mice
Mice, Inbred BALB C
Nanoparticles / chemistry*
Peptides / chemistry*
Polyglycolic Acid / chemistry*
Polylactic Acid-Polyglycolic Acid Copolymer
T-Lymphocytes / immunology*
Tumor Necrosis Factor-alpha / chemistry*

Substances

Adjuvants, Immunologic
Antigens, Protozoan
Peptides
Tumor Necrosis Factor-alpha
Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Lactic Acid