title: Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization.
abstract: Stabilization and ease of administration are two ways to substantially improve the use of current vaccines. In the present study an influenza whole inactivated virus (WIV) vaccine was freeze-dried or spray-freeze dried in the presence of inulin as a cryoprotectant. Only spray-freeze drying rendered powders compatible with administration to the lungs by insufflation. Pulmonary administration of the powder vaccine obtained by this method to BALB/c mice led to a transient influx of neutrophils and a concomitant decrease in the number of macrophages as did administration of liquid vaccine. Inflammatory reactions to both vaccines were mild and short-lived. Immunization studies showed that the immunogenic properties of WIV vaccine were not affected by drying. Pulmonary administration of the powder WIV vaccine induced a systemic immune response of the same magnitude as liquid vaccine while mucosal IgA responses were higher for powder WIV. In a challenge study where immunized mice were exposed to a lethal dose of live virus, two pulmonary doses of either liquid or powder WIV vaccine were equally effective as a single intramuscular injection of subunit vaccine in terms of reduction of the viral load in the lungs. To conclude, in the models employed for these studies the use of a dry powder WIV vaccine for pulmonary immunization was shown to be safe and efficient.
authors.affiliation: Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Sandrine A L
authors.initials: SA
authors.lastname: Audouy
authors.forename: Gieta
authors.initials: G
authors.lastname: van der Schaaf
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Jan
authors.initials: J
authors.lastname: Wilschut
authors.forename: Anke
authors.initials: A
authors.lastname: Huckriede
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003451:Cryoprotective Agents; D005260:Female; D005612:Freeze Drying; D006385:Hemagglutination Inhibition Tests; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007444:Inulin; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000821:virology; D011208:Powders; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D003451:Cryoprotective Agents; D007252:Influenza Vaccines; D011208:Powders; D015164:Vaccines, Inactivated; D007444:Inulin