title: Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus.
abstract: Type I IFN is a cytokine family endowed with multiple biological activities. In recent years, type I IFN has been demonstrated to play a crucial role in innate immunity, in dendritic cell maturation/differentiation and in the priming of primary antibody responses, especially when administered i.m. with a purified influenza vaccine. Due to the increasing interest in mucosal vaccination especially for respiratory infections, we investigated two different IFN-adjuvanted immunization protocols against influenza. In the first one, anesthesized C3H/HeN mice were instilled intranasally with 50 microl of a commercially available influenza vaccine containing 5 mg of hemagglutinin (HA) and a partially purified preparation of mouse IFN-alphal. A single intranasal administration of IFN-adjuvanted vaccine resulted in a full protection of 100% of mice against virus challenge while vaccine alone was only partially effective (40%). From the analysis of the specific antibody response emerged that type I IFN induced a significant increase of antibody titers in all the Ig subclasses with particular effect on IgG2a and IgA. To mimic aerosol administration and to limit vaccine delivery strictly to nasal mucosa, a second method of intranasal vaccination was developed in which mice were left awake and their nostrils moistened along the day of treatment (every 10 min) with six mini-doses (8 microl each) of vaccine +/- IFN-I with dose and timing equivalent to previous immunization protocol. This vaccination schedule prevented mice from pulmonary damage and the concomintant use of type I IFN induced an efficient and long lasting both local and systemic immune response. These findings shed new light on the involvement of type I IFN in the early phases of the immune response and open new and practical perspectives in vaccine research.
authors.affiliation: Department of Cellular Biology and Neurosciences, Istituto Superiore di Sanità, V. le Regina Elena 299, 00161 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bracci
authors.forename: Irene
authors.initials: I
authors.lastname: Canini
authors.forename: Massimo
authors.initials: M
authors.lastname: Venditti
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.forename: Simona
authors.initials: S
authors.lastname: Puzelli
authors.forename: Isabella
authors.initials: I
authors.lastname: Donatelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Proietti
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D018928:Immunity, Mucosal; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D007370:Interferon Type I