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.

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