Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques.

Measles remains an important cause of childhood mortality worldwide. Sustained high vaccination coverage is the key to preventing measles deaths. Because measles vaccine is delivered by injection, hurdles to high coverage include the need for trained medical personnel and a cold chain, waste of vaccine in multidose vials and risks associated with needle use and disposal. Respiratory vaccine delivery could lower these barriers and facilitate sustained high coverage. We developed a novel single unit dose, dry powder live-attenuated measles vaccine (MVDP) for respiratory delivery without reconstitution. We tested the immunogenicity and protective efficacy in rhesus macaques of one dose of MVDP delivered either with a mask or directly intranasal with two dry powder inhalers, PuffHaler and BD Solovent. MVDP induced robust measles virus (MeV)-specific humoral and T-cell responses, without adverse effects, which completely protected the macaques from infection with wild-type MeV more than one year later. Respiratory delivery of MVDP was safe and effective and could aid in measles control.

Deposition of albuterol aerosol generated by pneumatic nebulizer in the Sophia Anatomical Infant Nose-Throat (SAINT) model.

PURPOSE: To quantify distribution of albuterol aerosol generated by a pneumatic nebulizer within the nose and lungs of a model of a 9-month-old child (SAINT) and aerosol loss to the environment, during simulated breathing at increasing tidal volumes (TVs). METHODS: (99m)technetium-labeled albuterol aerosol was generated by an IPI nebulizer with face-mask. Deposition was quantified as a percentage of emitted dose using gamma scintigraphy. RESULTS: Lung deposition was similar for all TVs, averaging 7.17 +/- 0.01%, 9.34 +/- 0.01% and 9.41 +/- 0.02% at 50, 100 and 200 mL TV, respectively. In contrast, nose deposition increased significantly with TV, averaging 4.40 +/- 0.02%, 11.39 +/- 0.02% and 22.12 +/- 0.02% at 50 mL, 100 mL and 200 mL TV, respectively (all p < 0.0167). Aerosol loss to the environment was significantly lower at 200 mL TV (53.81 +/- 0.04%), compared to 50 mL (71.99 +/- 0.02%) (p < 0.0167). CONCLUSIONS: Our results suggest that nasal deposition of albuterol aerosol generated by a pneumatic nebulizer in 9-month-old infants may be significantly affected by changes in TV, ranging between 50 to 200 mL, whereas total lung deposition may not be affected. These results also predict that environmental losses would be highest when administering to a child breathing at 50 mL TV. These data should be useful to companies who are working to improve aerosol delivery systems to treat infants.

Safety and immunogenicity of dry powder measles vaccine administered by inhalation: a randomized controlled Phase I clinical trial.

BACKGROUND: Measles is a highly infectious respiratory disease which causes 122,000 deaths annually. Although measles vaccine is extremely safe and effective, vaccine coverage could be improved by a vaccine that is more easily administered and transported. We developed an inhalable dry powder measles vaccine (MVDP) and two delivery devices, and demonstrated safety, immunogenicity, and efficacy of the vaccine in preclinical studies. Here we report the first clinical trial of MVDP delivered by inhalation. METHODOLOGY: Sixty adult males aged 18 to 45 years, seropositive for measles antibody, were enrolled in this controlled Phase I clinical study. Subjects were randomly assigned in 1:1:1 ratio to receive either MVDP by Puffhaler(®) or by Solovent™ devices or the licensed subcutaneous measles vaccine. Adverse events (AEs) were recorded with diary cards until day 28 post-vaccination and subjects were followed for 180 days post-vaccination to assess potential serious long term adverse events. Measles antibody was measured 7 days before vaccination and at days 21 and 77 after vaccination by ELISA and a plaque reduction neutralization test. RESULTS: All subjects completed the study according to protocol. Most subjects had high levels of baseline measles antibody. No adverse events were reported. MVDP produced serologic responses similar to subcutaneous vaccination. CONCLUSIONS: MVDP was well tolerated in all subjects. Most subjects had high baseline measles antibody titer which limited ability to measure the serologic responses, and may have limited the adverse events following vaccination. Additional studies in subjects without pre-existing measles antibody are needed to further elucidate the safety and immunogenicity of MVDP.