title: Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice.
abstract: An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.
authors.affiliation: Institute of Bioengineering.
authors.forename: Marie
authors.initials: M
authors.lastname: Ballester
authors.affiliation: Institute of Bioengineering.|Swiss Institute for Experimental Cancer Research (ISREC).
authors.forename: Laura
authors.initials: L
authors.lastname: Jeanbart
authors.affiliation: Institute of Bioengineering.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Titta
authors.affiliation: Institute of Bioengineering.
authors.forename: Chiara
authors.initials: C
authors.lastname: Nembrini
authors.affiliation: Faculty of Biology and Medicine, Université de Lausanne (UNIL), Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.affiliation: Institute of Bioengineering.|Institute for Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland.|Institute for Molecular Engineering, University of Chicago, USA.|Materials Science Division, Argonne National Laboratory, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.affiliation: Institute of Bioengineering.|Swiss Institute for Experimental Cancer Research (ISREC).|Institute for Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland.|Institute for Molecular Engineering, University of Chicago, USA.
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000627:therapeutic use*; D039981:Pyroglyphidae / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides