Needle-free Inhalable Dry Powder Aerosol Measles Vaccine Developed for Pulmonary Delivery with a PuffHaler DPI

Robert E. Sievers(1), Stephen P. Cape(1) and Lia G. Rebits (1)

Abstract
An inhalable dry powder aerosol measles vaccine has been developed by our group for pulmonary delivery with a PuffHaler dry powder inhaler (DPI). Phase I clinical trials in adult volunteers have recently been completed without adverse events (Agarkhedkar S., P.S. Kulkarni, S. Winston, R. Sievers R.M. Dhere, B. Gunale, K. Powell, P.A. Rota, M. Papania, S. Cape, A. Chaudhan, V. Vaidya, R. Mulay, S Agarkhedkar, C. Shermer, M. Collins, R. Anderson, “Safety and immunogenicity of dry powder measles vaccine administered by inhalation: A randomized controlled Phase I clinical trial.” In Press, Vaccine (2014), http://dx.doi.org/10.1016/j.vaccine.2014.09.071). One goal of developing an inhalable dry powder aerosol was to take advantage of the mucosal immunity of the respiratory tract. This is the first report to our knowledge of successful Phase I trials of a finely divided dry powder aerosol vaccine. The advantages of using a dry powder inhaler, such as the PuffHaler® are numerous. No needle is required, so needle contamination is avoided in resource-poor settings. High-purity, sterile water for injection is required to reconstitute the traditional vaccine, but not with this new inhaled vaccine. No skilled care-givers to perform injections are needed. The dry powder, prepared by Carbon-Dioxide Assisted Nebulization with a Bubble Dryer® (CAN-BD) has a shelf-life of four years at 2-8 °C. We developed a new stabilizing sugar formulation consisting of substituting myo-inositol in place of sorbitol, which is used in the Edmonston-Zagreb injected vaccine manufactured by the Serum Institute of India, Ltd.