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| |  Childhood vaccines that can be inhaled and delivered directly to mucosal surfaces have the potential to offer significant advantages over injection, the most common way vaccines are given today. Not only might they reduce the risk of infection from HIV, hepatitis, and other serious diseases due to unsterilized needles, they may prove more effective against disease. Many serious infections, such as the measles virus, can enter the body through inhalation. Vaccine delivery systems that can target respiratory mucosal tissue and stimulate immune response there have the potential to be particularly effective against these types of infections.
Some 3 million children have been immunized against measles by inhaling wet mist vaccine aerosol. In children treated with the wet aerosol during a measles outbreak, the attack rate was 0.8 percent, compared with 14 percent for those who had received vaccine via injections. But while the wet mists are effective, they require power to generate aerosols, and the liquid vaccines must be freshly made up and kept on ice.
Collaborating with an international group that includes the Serum Institute of India (SII), the U.S. Centers for Disease Control and Prevention (CDC), the University of Colorado, and private companies, Dr. Sievers and his colleagues at Aktiv-Dry, LLC (AD) are developing a dry-powder version of the measles vaccine that can be inhaled through a disposable plastic device.
In 2008, investigators plan to begin safety and toxicology tests on the new vaccine formulations in rodents and non-human primates. Phase I clinical trials are scheduled to start in 2009. |
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| | | Synthesize a dry powder Edmonston-Zagreb measles vaccine that can be administered to the respiratory tract by inhalation. The investigators are using CU’s and Aktiv-Dry’s Carbon Dioxide Assisted Nebulization with a Bubble Dryer® to prepare microparticles | | | | | Design and fabricate one or two inexpensive, single-dose devices to deliver microparticles to the respiratory tracts of 1-4 year olds as well as older subjects | | | | | Perform pre-clinical assessment in vitro in human upper airway epithelial cell cultures, and in vivo mouse plaque neutralization studies and in Cotton rats | | | | | Assess safety of the vaccine in non-human primates | | | | | Evaluate clinically in Phase 1 trials | | | | | Scale-up powder stabilization and good manufacturing practice (GMP) and establish manufacturing and packaging in blister packs or capsules | | |
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| | | Substituting the stabilizing sugar myo-inositol for sorbitol, investigators reformulated SII’s commercial lyophilized measles vaccine cakes into dispersible microparticles that can be inhaled to coat the respiratory tract, including the alveoli; The myo-inositol based live attenuated measles vaccine passed the WHO test of heating at 37°C for seven days with less than 1 log loss of viral activity as measured by plaque neutralization assay. | | | | | The team demonstrated that, in terms of large fine particle fraction and emitted dose, prototypes of two new active dry powder inhalers, AD’s PuffHaler and BD’s Solovent, are comparable in performance to the FDA¬approved active dry powder inhaler (DPI) for lung deposition of insulin. | | | | | Both needle-free DPIs showed promising results when tested with the newly reformulated measles vaccine in Cotton rats breathing from aerosol reservoirs. Delivery of measles vaccine powder to the alveoli was confirmed by real time polymerase chain reaction (PCR). In Cotton rats exposed to aerosol boluses of 10, 20, or 30 mg, evidence of viral replication and measles antibody formation in the deep lungs appeared after 28 days. The plaque neutralization dose response curves were similar for the aerosols delivered by both the PuffHaler and Solovent. Increased dose and longer duration of exposure to the aerosol cloud resulted in better alveolar deposition and better immune response, leading investigators to conclude that both DPIs emit a sufficient dose with effective particle sizes that can be inhaled by an animal and induce an immune response to measles. | | | | | These tests confirmed and extended earlier conclusions based on tests with CD46 transgenic mice and human upper airway epithelial cell cultures that the fine dry powders are rapidly rehydrated and propagate on moist surfaces. | | |
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| | | Centers for Disease Control and Prevention, Georgia, United States - US | | | | | BD Technologies, North Carolina, United States - US | | | | | Ferro-Pfanstiehl, Ohio, United States - US | | | | | National Jewish Medical and Research Center, Colorado, United States - US | | | | | Johns Hopkins University, Baltimore, Maryland, United States - US | | | | | University of Maryland, Maryland, United States - US | | | | | Centre International de Toxicologie, Evreux, France - FR | | | | | ZymoGenetics, Washington, United States - US | | | | | University of Kansas, Kansas, Missouri, United States - US | | | | | University of Colorado, Colorado, United States - US | | | | | Serum Institute of India, Pune, India - IN | | |
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