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

Description

DESCRIPTION provided by applicant Sanariaandapos s platform technology is production of aseptic purified cryopreserved Plasmodium falciparum Pf sporozoites SPZ This technology has produced three products administered by needle and syringe all of which are in clinical trials PfSPZ Vaccine radiation attenuated PfSPZ PfSPZ Challenge infectious PfSPZ for controlled human malaria infection CHMI and PfSPZ CVac PfSPZ Challenge given with antimalarial drugs as a vaccine PfSPZ Vaccine protected volunteers against CHMI in a clinical trial at the NIH The reproducibility of the NIH findings durability of protection protection against heterologous Pf parasites and reduced numbers of doses with altered vaccine regimens are being assessed in clinical trials at sites in the U S Europe and Africa By March our Malian collaborators had injected andgt volunteers twice at a week interval by direct venous inoculation DVI the injections have gone perfectly and been extremely well tolerated clinical trials of PfSPZ Challenge have been conducted in countries infection was achieved in five of the trials A trial of the PfSPZ CVac approach begins in Germany in May There is tremendous international support for our whole PfSPZ approach for malaria vaccines and products for CHMI Sanariaandapos s products rely on production of PfSPZ in aseptic mosquitoes Our Phase I SBIR project proposed developing a method for producing PfSPZ in culture in vitro that would eliminate the need for mosquitoes We estimated this would reduce cost of producing vaccine by The Phase I SBIR was successful We developed methods for producing Pf oocysts in vitro with an efficiency times greater than when we produce oocysts in mosquitoes We repeatedly produced PfSPZ in vitro that invaded and developed to mature day liver stage schizonts expressing Pf merozoite surface protein with the same efficiency as PfSPZ freshly dissected from mosquitoes This is a andquot firstandquot in the history of malaria research Although we will significantly improve efficiency and quality of in vitro production of PfSPZ in Phase II we could now actually manufacture enough PfSPZ in vitro to support a CHMI clinical trial of PfSPZ Challenge in vitro In this Phase II projet we will optimize methods for manufacture of clinical grade PfSPZ in vitro We will use D cell culture technologies to fully optimize methods for production of PfSPZ in vitro and then demonstrate these PfSPZ can reproducibly invade and develop in human hepatocytes in vitro and in vivo and complete the Pf life cycle This will be done in vivo using human liver chimeric mice transfused with human blood We will establish a method for purifying PfSPZ and an assay for quantifying purity Our manufacturing quality and regulatory teams will ensure all reagents and processes are compliant with cGMPs and adequate for manufacturing conduct engineering runs and submit a pre IND package to FDA for a CHMI clinical trial of PfSPZ Challenge in vitro to demonstrate infectivity to humans thereby establishing a rationale for moving from mosquito to in vitro produced PfSPZ for our vaccines PUBLIC HEALTH RELEVANCE A highly effective malaria vaccine would have an enormous public health benefit Sanariaandapos s attenuated malaria sporozoite vaccine PfSPZ Vaccine has been found to be highly effective in clinical trials Currently the PfSPZ Vaccine is manufactured using aseptic mosquitoes This project aims to establish methods for the manufacture of PfSPZ Vaccine in vitro thereby eliminating the need for mosquitoes at any stage in the manufacturing process and thereby reducing cost of goods by approximately