title: Virus-like nanostructures for tuning immune response.
abstract: Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Rashad
authors.initials: R
authors.lastname: Mammadov
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Goksu
authors.initials: G
authors.lastname: Cinar
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Nuray
authors.initials: N
authors.lastname: Gunduz
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Melis
authors.initials: M
authors.lastname: Goktas
authors.affiliation: Adult Hematology Laboratory, School of Medicine, Gazi University, Ankara 06500, Turkey.
authors.forename: Handan
authors.initials: H
authors.lastname: Kayhan
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Sehmus
authors.initials: S
authors.lastname: Tohumeken
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Ahmet E
authors.initials: AE
authors.lastname: Topal
authors.affiliation: Department of Physics Engineering, Hacettepe University, 06800, Ankara, Turkey.
authors.forename: Ilghar
authors.initials: I
authors.lastname: Orujalipoor
authors.affiliation: Hacettepe University and Diskapi Research and Training Hospital, 06800, Ankara, Turkey.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Delibasi
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Aykutlu
authors.initials: A
authors.lastname: Dana
authors.affiliation: Department of Physics Engineering, Hacettepe University, 06800, Ankara, Turkey.
authors.forename: Semra
authors.initials: S
authors.lastname: Ide
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Ayse B
authors.initials: AB
authors.lastname: Tekinay
authors.affiliation: Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.
authors.forename: Mustafa O
authors.initials: MO
authors.lastname: Guler
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004705:Endocytosis; D007109:Immunity; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D057139:Nanofibers / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D059372:Nucleotide Motifs; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure
chemical_list: D000941:Antigens; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D051217:Toll-Like Receptor 9; D058425:Vaccines, Virus-Like Particle