Inactivated Polio Vaccine (IPV) and Oral Polio Vaccine (OPV) manufactured today are both unstable at high ambient temperatures (i.e. +37°C) and require maintenance of a cold chain to prevent potency loss during transportation and storage. OPV is most sensitive to heat, and IPV is sensitive to both freezing and elevated temperatures. OPV live vaccines, created from attenuated Sabin strains, are shed from the vaccines and circulated in the environment, and have a risk of reversion to virulence. IPV manufacturing is very expensive due to the need to grow virulent wildtype strains and then chemically inactivate them, which decreases potency and requires high doses to be effective. Cold chain dependence coupled with the high cost associated with manufacturing, distributing, administering, and storing IPV has limited its use primarily to industrialized countries. In this Phase I ?proof of concept? project, Universal Stabilization Technologies Inc. will stabilize Type 1 Sabin OPV using its patented ?Preservation by Vaporization? technology that immobilizes the viruses in glassy carbohydrate foams. Sabin inactivated vaccine (sIPV) will be produced by inactivation of PBV-preserved OPV using electron beam (EB) irradiation, which targets the nucleic acids of PBV-preserved biologics with minimal damage to vaccine epitopes. EB inactivation does not require use of toxic chemicals, is less expensive, and opens the prospect of producing more potent, cheaper and safer vaccines. The foams will then be micronized to produce powders with particle size about 20-30 µm, appropriate for respiratory delivery and for incorporation into capsules and dissolvable polymeric films for oral delivery. After micronization the thermostabilized, inactivated sIPV powders will be placed on stability storage at freezing temperature (-20°C), room temperature (25°C) and high ambient temperature (37°C) for 2 months. Testing for antigenicity which remains after incubation at low pH (simulating stomach acid conditions) and neutral pH will be done initially after inactivation, and after two months of stability storage. Activity will be measured utilizing a D-antigen ELISA assay. The stability specification will be set at no more than 0.5 log antigenicity loss allowed after 2 months at each temperature. The most promising formulations will be integrated into each of two delivery devices: 1) a respiratory powder delivery device and 2) films and capsules for oral delivery. These preparations will be carried forth into Phase II research to test the most promising formulation and delivery device in an appropriate animal model. The ultimate goal of this project is to develop a thermostable, Sabin-based inactivated polio vaccine for mucosal (oral and intranasal) administration. Phase 1 will involve development and evaluation of the thermostable sIPV product and encapsulation into mucosal delivery devices, and in Phase II UST will evaluate and optimize delivery in appropriate animal models. Project Te
