title: Induction of a balanced Th1/Th2 immune responses by co-delivery of PLGA/ovalbumin nanospheres and CpG ODNs/PEI-SWCNT nanoparticles as TLR9 agonist in BALB/c mice.
abstract: To develop effective and safe vaccines with reduced dose of antigen and adjuvant, intelligent delivery systems are required. Many delivery systems have been developed to enhance the biological activity of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODN) as both immunotherapeutic agents and vaccine adjuvants. In this study we designed a novel CpG ODN delivery system based on single-walled carbon nanotube (SWCNT) functionalized with polyethylenimine (PEI) and alkylcarboxylated PEI (AL-PEI). The physicochemical characteristics, cytotoxicity and cellular uptake studies of these carriers were performed. All carriers were conjugated with CpG ODN followed by co-delivery with ovalbumin (OVA) encapsulated into poly (lactic-co-glycolic acid) nanospheres (PLGA NSs) to enhance the induction of immune responses. The effect of these formulations on antibody (IgG1, IgG2a) and cytokine (IL-1β, IFN-γ, IL-4) production was evaluated in an in vivo experiment. The results showed that all nano-adjuvant formulations had a strong influence in up-regulation of IFN-γ and IL-4 in parallel with high IgG1-IgG2a isotype antibody titers in mice. In particular, SWCNT-AL-PEI nano-adjuvant formulation generated a balanced Th1 and Th2 immune response with more biased toward Th1 response without exhibiting any inflammatory and toxic effects. Therefore this nano-adjuvant formulation could be used as an efficient prophylactic immune responses agent.
authors.affiliation: Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Immunology Section, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Ebrahimian
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Maleki
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Hashemitabar
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran; Immunology Section, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: haghparast@um.ac.ir.
authors.forename: Alireza
authors.initials: A
authors.lastname: Haghparast
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D005260:Female; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D037742:Nanotubes, Carbon; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011094:Polyethyleneimine; D010047:Ovalbumin
keywords: Adjuvant delivery; CpG ODN; Ovalbumin; PLGA; Polyethylenimine; Single-walled carbon nanotubes