title: Oral spray immunization may be an alternative to intranasal vaccine delivery to induce systemic antibodies but not nasal mucosal or cellular immunity.
abstract: Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist, OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.
authors.affiliation: Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway. hilde.bakke@fhi.no
authors.forename: H
authors.initials: H
authors.lastname: Bakke
authors.forename: H H
authors.initials: HH
authors.lastname: Samdal
authors.forename: J
authors.initials: J
authors.lastname: Holst
authors.forename: F
authors.initials: F
authors.lastname: Oftung
authors.forename: I L
authors.initials: IL
authors.lastname: Haugen
authors.forename: A-C
authors.initials: AC
authors.lastname: Kristoffersen
authors.forename: A
authors.initials: A
authors.lastname: Haugan
authors.forename: L
authors.initials: L
authors.lastname: Janakova
authors.forename: G E
authors.initials: GE
authors.lastname: Korsvold
authors.forename: G
authors.initials: G
authors.lastname: Krogh
authors.forename: E A S
authors.initials: EA
authors.lastname: Andersen
authors.forename: P
authors.initials: P
authors.lastname: Djupesland
authors.forename: T
authors.initials: T
authors.lastname: Holand
authors.forename: R
authors.initials: R
authors.lastname: Rappuoli
authors.forename: B
authors.initials: B
authors.lastname: Haneberg
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000378:metabolism; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D012463:Saliva / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007252:Influenza Vaccines