SANARIA INC. — Department of Health and Human Services SBIR Phase II: NIAID

Description

ABSTRACT Sanaria s Plasmodium falciparumPfsporozoiteSPZvaccines development program is receiving global supportTrials of PfSPZ Vaccineradiation attenuated PfSPZor PfSPZ CVacPfSPZ Chemoprophylaxis Vaccineadministered by direct venous inoculationDVIincludingadults to infants were initiated in DecemberTanzaniaU Sor will be initiated in earlyin MaliKenyainfantsGhanaEquatorial GuineaGermany andadditional U SsitesThese trials will assessordose regimensasprotective efficacy atweeks after last dose has been established with adose regimenProtective efficacy has been shown to be durable against controlled malaria infectionCHMIfor at least a yearand against intense natural transmission in Mali of heterogeneous strains of Pf for at leastmonthsPfSPZ Vaccine and PfSPZ CVac are comprised of PfSPZ of the NFstrain of PfShort term protectionweeksby PfSPZ Vaccine against a heterologousdifferent from the vaccine strainCHMI with Pf Gparasites wasbut despite a significant delay in onset of parasitemiamonth sterile protective efficacy was onlySanaria is taking two approaches to improving protective efficacy against heterologous heterogeneous strainsThest is to increase the dose of PfSPZNFper immunization based on the hypothesis that this will broaden and strengthen the protective immune responses against shared dominant and sub dominant epitopesAll of the trials described above utilize this approachThend and potentially more efficient approach will be to combine PfSPZ from different strains of Pf in the same vaccineOur analysis of genomic sequence datapredicted proteomesand predicted T cell epitopes indicates that using two strains of Pf should be sufficientThis project fills an important gapWe have funding from VRCNIAIDNIH to conduct a clinical trial of a multivalent PfSPZ vaccinebut require the funds to manufacturecharacterizeand release the multi valent vaccineand to navigate the regulatory clinical affairs pathways required to initiate the trialIn this Phase IIB SBIR projectwe propose toManufacture and QC release chloroquine sensitive PfSPZ Challenge of a W African Pf cloneNFthat can be used for CHMI studies and as a component of a multi strain PfSPZ CVacManufacture and release PfSPZ Vaccine based on the Brazilian Pf cloneGand PfSPZ VaccineNFfor a two strain clone PfSPZ Vaccine combinationManufacture and release PfSPZ ChallengeGand PfSPZ ChallengeNFfor a two strain combination PfSPZ CVacandConduct an end of phasemeeting with FDA to propose and finalize a plan for using phaseCHMI trials with PfSPZ ChallengeNFGNFCand NFto replace phasefield trials to establish protective efficacy of the vaccinesSuccess will reduce the time to licensure of a PfSPZ vaccine for travelers military by at least a year and save andgt$MIt will also facilitate more rapid development of all pre erythrocytic stage vaccines intended to provide the high levelandgtprotection required for a vaccine for travelersmilitaryand elimination campaigns PROJECT NARRATIVE Since inception this SBIR has been focused on providing the foundation for moving to a multivalent approach to vaccination if neededa multi strain clone approach to controlled human malaria infection with Sanaria s Plasmodium falciparumPfsporozoiteSPZbased productsIn this new project we will develop an optimizedstrain clone vaccine and multi strain clone controlled human malaria infection systemand an optimized approach for a travelers military vaccine for pivotal phasetrials that takes advantage of these key parasitesand thereby significantly reduces the time and cost to achieve vaccine licensure and commercial launch