title: Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment.
abstract: The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB409-505 and gD301-309, selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 ⋅ 10(-7) mol ⋅ Kg(-1); hydrodynamic radii (RH) between 50-80 nm, and a zeta potential (ζ) around - 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 μM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.
authors.affiliation: Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy ; Department of Clinical Pathology and Transfusion Medicine, University Hospital "Ruggi d'Aragona", Salerno, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Vitiello
authors.affiliation: Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Galdiero
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Finamore
authors.affiliation: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Martora
authors.affiliation: Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Mansi
authors.affiliation: Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ringhieri
authors.affiliation: Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008823:Micelles; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000494:pharmacology; D020298:U937 Cells; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008823:Micelles; D010455:Peptides; D013501:Surface-Active Agents; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C515577:glycoprotein gD, herpes simplex virus type 1
keywords: HSV; epitopes; self-adjuvant vaccine