Development of a thermostable, electron beam inactivated Sabin-based polio vaccine for mucosal delivery

Project Summary AbstractInactivated Polio VaccineIPVand Oral Polio VaccineOPVmanufactured today are both unstable at high ambient temperaturesi eCand require maintenance of a cold chain to prevent potency loss during transportation and storageOPV is most sensitive to heatand IPV is sensitive to both freezing and elevated temperaturesOPV live vaccinescreated from attenuated Sabin strainsare shed from the vaccines and circulated in the environmentand have a risk of reversion to virulenceIPV manufacturing is very expensive due to the need to grow virulent wildtype strains and then chemically inactivate themwhich decreases potency and requires high doses to be effectiveCold chain dependence coupled with the high cost associated with manufacturingdistributingadministeringand storing IPV has limited its use primarily to industrialized countriesIn this Phase Iproof of conceptprojectUniversal Stabilization Technologies Incwill stabilize TypeSabin OPV using its patentedPreservation by Vaporizationtechnology that immobilizes the viruses in glassy carbohydrate foamsSabin inactivated vaccinesIPVwill be produced by inactivation of PBV preserved OPV using electron beamEBirradiationwhich targets the nucleic acids of PBV preserved biologics with minimal damage to vaccine epitopesEB inactivation does not require use of toxic chemicalsis less expensiveand opens the prospect of producing more potentcheaper and safer vaccinesThe foams will then be micronized to produce powders with particle size aboutmappropriate for respiratory delivery and for incorporation into capsules and dissolvable polymeric films for oral deliveryAfter micronization the thermostabilizedinactivated sIPV powders will be placed on stability storage at freezing temperatureCroom temperatureCand high ambient temperatureCformonthsTesting for antigenicity which remains after incubation at low pHsimulating stomach acid conditionsand neutral pH will be done initially after inactivationand after two months of stability storageActivity will be measured utilizing a D antigen ELISA assayThe stability specification will be set at no more thanlog antigenicity loss allowed aftermonths at each temperatureThe most promising formulations will be integrated into each of two delivery devicesa respiratory powder delivery device andfilms and capsules for oral deliveryThese preparations will be carried forth into Phase II research to test the most promising formulation and delivery device in an appropriate animal modelThe ultimate goal of this project is to develop a thermostableSabin based inactivated polio vaccine for mucosaloral and intranasaladministrationPhasewill involve development and evaluation of the thermostable sIPV product and encapsulation into mucosal delivery devicesand in Phase II UST will evaluate and optimize delivery in appropriate animal models Project Narrative Inactivated polio vaccine and orallivepolio vaccines distributed today are unstable at high ambient temperatures and require maintenance of a cold chain to prevent potency loss during transportation and storageAdditionallywith the current live oral polio vaccinethere is shedding and a risk of reversion to virulence which could cause additional infectionsThe intended goal of this project is to produce a thermostableSabin based inactivated polio vaccine for mucosaloral and intranasaldelivery which would contribute to the missions of WHO and Global Polio Eradication Initiative for world wide eradication of polio due to its enhanced safetylower cost and ease of storage transport