Development of a thermostable rotavirus vaccine for mucosal delivery withoutneed for reconstitution - Phase II

PROJECT SUMMARY ABSTRACTRotavirusRVis responsible for an estimateddeaths each year from severe diarrheamostly in children in developing countriesCurrently only two RV vaccines are broadly availableand are delivered by liquid dropseither directly or after reconstitutionto infants betweenweeks of ageBoth vaccines are labile at ambient temperatures and so bound by the cold chainas well as being sensitive to freezing because of their liquid componentsA drawback of liquid delivery to babies is the potential for spitting out the vaccinewhich increases the risk of under vaccinationAlsoaside from leaving babies unprotected from RV during the crucial first months of lifethe protocol of vaccinating only afterweeks old has been found to lead to greater rates of vaccine associated intussusceptiona potentially fatal bowel blockageFurthermorethe cost of these vaccines is often prohibitively high for introduction in the poorest countrieswhich have the highest rates and burden of RV gastroenteritisThus there is an urgent need to develop a cost effective thermostable rotavirus vaccine for liquid free administration during the neonatal time periodInternational Medica FoundationIMFhas world wide license for a low cost liquid RV vaccineRRV TVand has designed an improved neonatal administration protocol which data indicates will reduce the rate of intussusceptionThis vaccine was developed as a public private partnership project and has finished Phase II clinical trials in Ghanaand will seek WHO Prequalification for supply to UN agencies in the near futureUST s patented Preservation by VaporizationPBVstabilization technology and techniques for producing polymeric films containing PBV dried biologicals enable buccal vaccine delivery in the dry film formatIn Phase I studies with RV vaccineUST has proven that PBV dried vaccine in polymeric film retains high activity and long term stability formonths atC andmonths atCThe application of these technologies for use with RRV TV will decreased the cost of vaccine implementation due to the low priced raw vaccine materialenhanced manufacturing yields possible with PBVand refrigeration free distribution and storageThe final product will be a thermostable RV vaccine in a mucoadhesive dissolvable polymeric film for liquid free administration to the buccal or sublingual surfacesto provide simplermore accurate dosing to neonatesThe specific objectives of this Phase II project areApplication of PBV protocols developed during Phase I to tetravalent RRV TV vaccineOptimization of film production protocols to incorporate PBV RRV TV vaccine and antacidsanddemonstrate film suitability and safety in vitro as well as in vivo using hamsters and ratsand in vivo vaccine immunogenicity and efficacy against challenge in a gnotobiotic piglet modelThe long term goal is to generate a dissolvable mucoadhesive polymeric film that contains thermostable RRV TV rotavirus vaccine for simple oral mucosal delivery to neonates which has low cost of manufacturestore and ship and is immunogenicsafe and protective