James J. Barry

Nebulized Live-Attenuated Influenza Vaccine Provides Protection in Ferrets at a Reduced Dose

Live-attenuated influenza vaccine (LAIV) is delivered to vaccine recipients using a nasal spray syringe. LAIV delivered by this method is immunogenic at current doses; however, improvements in nasal delivery might allow for significant dose reduction. We investigated LAIV vaccination in ferrets using a high efficiency nebulizer designed for nasal delivery. LAIV nasal aerosol elicited high levels of serum neutralizing antibodies and protected ferrets from homologous virus challenge at conventional (10(7)TCID(50)) and significantly reduced (10(3)TCID(50)) doses. Aerosol LAIV also provided a significant level of subtype-specific cross-protection. These results demonstrate the dose-sparing potential of nebulizer-based nasal aerosol LAIV delivery.

Intranasal Deposition of Accuspray™ Aerosol in Anatomically Correct Models of 2-, 5-, and 12-Year-Old Children

BACKGROUND To our knowledge, quantification of intranasal deposition of aerosol generated by Accuspray(™) (AS) in children has never been published. We hypothesized that deposition would vary significantly with age and with placement of the device within, or outside, of the nostril. METHODS We tested these hypotheses in anatomically-correct physical models based on CT scans of 2-, 5-, and 12-year-old children with normal, intranasal airways. Models included a removable anterior nose (AN) with exterior facial features and interior nasal vestibule and nasal valve area and a main nasal airway (MNA), subdivided into upper (superior turbinates and olfactory area), middle (middle turbinates), and lower (inferior turbinates and nasopharynx) thirds. Aerosol was generated from distilled water admixed with (99m)technetium pertechnetate and administered during static airflow by AS inserted inside the right nostril (eight runs/model), or outside the right nostril (six runs/model). Mean aerosol Dv(50) ± standard deviation was 67.8 ± 24.7 μm. Deposition was quantified by 2D gamma scintigraphy and expressed as percentage of the emitted dose. RESULTS When placed inside the nostril, mean (± standard deviation) deposition within the MNA was significantly less in the 2-year-old, compared to the 5- and 12-year-old, averaging 46.8 ± 33.8% (AN:55.4 ± 29.9%), 75.4 ± 26.7% (AN:23.3 ± 13.6%), and 72.1 ± 18.5% (AN:25.8 ± 18.5%), respectively (p<0.05). When placed outside the nostril, MNA was significantly less in the 2- and 5-year-old compared to the 12-year-old, with 1.4 ± 2.5% (AN:69.7 ± 40.7%), 7.4 ± 9.0% (AN:77.8 ± 32.8%), and 21.1 ± 29.1% (AN:29.2 ± 19.3%), respectively (p<0.05). Deposition in the MNA of all age models was highest when AS was placed inside the nostril (p<0.05). Deposition in the lower third was significantly increased for the 5- and 12-year-old and in the middle third of the 5-year-old when AS was placed inside the nostril. CONCLUSIONS These results indicate that age and device placement play important roles in terms of intranasal deposition, when administering aerosol with Accuspray(™) to children.