Pre-clinical Commercialization of a Synthetically Designed, Live-attenuated RSV Vaccine

Project Summary Abstract A current unmet clinical need is a commercial vaccine to protect at risk populationsthe very young and the elderlyagainst Respiratory Syncytial VirusRSVa respiratory pathogen that annually in the US causeshospitalizations andmillion outpatient visits in children ltyears old and rtdeaths in those overThe burden of this pathogen is even more pronounced in the developing worldIn this Direct to Phase II projectwe will further commercialize candidate liveattenuated RSV vaccine strain we have developed using our vaccine design platformSAVESynthetic Attenuated Virus EngineeringColemanet alScienceSAVE is unlike any vaccine platform previously investigatedit does not use blind serial passagingan attenuated carrier backbone virusor virus like particlesSAVE utilizes genome de optimizationand synonymous recoding of viral ORFs to yield live attenuated vaccine strains and has shown proof of concept in seven unique virusesThese designer vaccine strains areantigenically identical to the wild type and present all antigens of the target virusOur SAVE designed RSV vaccine strains were developed in collaboration with pre eminent RSV scientist DrPeter Collins of NIH NIAIDWe now have lead candidateRSV MinAthat is highly attenuated and shown to induce immunity in non human primatesefficacy in Cotton Ratsand the recently demonstrated ability to neutralize human clinical RSV isolates of A and B subtypesFurthermorewe have demonstrated genetic and phenotypic stability of MinA after serial passageBased on our early success in primatesin AugustCodagenix was granted a second no fee NIAID DMID service contractVMRDBPOKimin support of this project to execute Process Development to develop a cGMP compliant manufacturing process for our lead RSV vaccine candidate MinA in preparation of cGMP manufacturing of clinical lotsVaccine commercialization is a costly and multi faceted development process that requires adherence to regulatory guidelines set by the FDAThereforein this project we seek funds to support the other areas of pre clinical development of these SAVE designed RSV vaccine strainsThese experiments include continued assaying for genetic phenotypic stabilitycGMP Master Cell Bank construction and characterizationcGMP clinical vaccine lot manufacturingand GLP toxicologyAt the end of this projectwe will have produced a SAVE RSV vaccine candidate ready for a Phase I clinical trialThe overall goal of the proposed work is to further commercialize a live attenuated RSV vaccine that will be administered intranasallyIn the initial phases of this effortpilot data akin to a Phase I SBIR grantCodagenixin collaboration with DrPeter Collins at NIHdeveloped and characterized three promising RSV vaccine candidatesEfficacysafetyand demonstration of the induction of a crossreactive immune response has now narrowed this field of candidates to a single candidateRSVMinAready for cGMP manufacturingWe seek funds to support all other aspect of pre clinical development to prepare this RSV vaccine for a Phase I trial