title: Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice.
abstract: Immunotherapy (IT) by injection more readily induces clinical tolerance to stinging insects than to respiratory allergens. However, while systemic immunization induces adaptive responses systemically, the induction of mucosal immunity generally requires local Ag exposure. Taken together, these observations suggest that the poor success rate of systemic IT for asthma could be a consequence of inadequate immune modulation in the airways. In support of this position, investigations presented in this report demonstrate that allergen IT more effectively induces airway allergen tolerance in Th2-sensitized mice, when delivered by the intranasal (i.n.) vs the intradermal (i.d.) route. Moreover, compared with native allergen, allergen immunostimulatory sequence oligodeoxynucleotide conjugate proved to be a more effective i.n. IT reagent for protecting allergic mice from airway hypersensitivity responses. Furthermore, for both native allergen and allergen immunostimulatory sequence oligodeoxynucleotide conjugate, i.n. and i.d. IT delivery were similarly effective in modulating systemic immune profiles in Th2-sensitized mice, while only i.n. IT had significant immunomodulatory activity on B and T cell responses in the airways. The present investigations may be the first to suggest that i.n. IT is more effective than i.d. IT for the treatment of asthma. Furthermore, our results suggest that modulating airway rather than systemic immunity may be the more important therapeutic target for the induction of clinical tolerance to respiratory allergens.
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takabayashi
authors.forename: Lev
authors.initials: L
authors.lastname: Libet
authors.forename: Dugald
authors.initials: D
authors.lastname: Chisholm
authors.forename: Jose
authors.initials: J
authors.lastname: Zubeldia
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Horner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D018899:CpG Islands / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin