Dry powder aerosol vaccine and antibiotics delivery development to reduce risks of deaths in developing countries


Robert E. Sievers, Bob.sievers@colorado.edu, CIRES, Department of Chemistry and Biochemistry, and Center for Pharmaceutical Biochemistry, University of Colorado, 215 UCB, Boulder, CO 80309-0215
The focus of our Gates Grand Challenges in Global Health project is to develop needle-free vaccine delivery systems. 1) Our team has reformulated the injectable Edmonston-Zagreb live attenuated measles virus vaccine, replacing sorbitol with myo-inositol. Our patented CAN-BD process was used to produce micronized measles vaccine dry powder with residual moisture levels of 0.3%-1.3%. The dry powder vaccine is stable for at least 1 year at 2-8 C and shows less than 1 log loss of virus infectivity at 37 C for 7 days. 2) We have demonstrated that inhaled myo-inositol powders are non-toxic in a GLP toxicology study in Sprague-Dawley rats. 3) Our team has developed two simple, low cost active dry powder inhalers (DPIs) with performances virtually equivalent to an FDA-approved active inhaler. 4) In two established measles vaccine animal models, Cotton rats and rhesus macaques, our active DPI's delivered aerosolized measles vaccine dry powder by at-liberty breathing. The microparticles rapidly dissolve and the virus replicates in the aqueous film in respiratory tracts so no water-for-injection is needed. The dry powders are individually sealed in peelable blister packs or rupturable capsules to minimize bacterial contamination encountered in multi-dose vials. Delivery of the powder to the lungs, followed by viral replication, was confirmed by RT-PCR. A measles-specific immune response was also demonstrated. In macaques our vaccine formulation induced high avidity, neutralizing antibodies and T-cell responses equal to or better than that seen with injected liquid vaccine. Measles vaccine dry powders in unit dose packaging have the potential to effectively vaccinate infants, children, and adults by inhalation, avoiding many of the problems associated with liquid vaccines delivered by injection. Supported in part by FNIH.