title: Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles.
abstract: We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.
authors.affiliation: Department of Pharmaceutical Sciences, University of Piemonte Orientale Amedeo Avogadro, Via Bovio 6, 28100 Novara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fallarini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Paoletti
authors.forename: Carolina Orsi
authors.initials: CO
authors.lastname: Battaglini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ronchi
authors.forename: Luigi
authors.initials: L
authors.lastname: Lay
authors.forename: Renato
authors.initials: R
authors.lastname: Bonomi
authors.forename: Satadru
authors.initials: S
authors.lastname: Jha
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mancin
authors.forename: Paolo
authors.initials: P
authors.lastname: Scrimin
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology*; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D020099:Coated Materials, Biocompatible; D016207:Cytokines; D008070:Lipopolysaccharides; D006046:Gold