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

Description

DESCRIPTION provided by applicant We build on the successful work in Phase II SBIR R AI in which a genetically attenuated Plasmodium falciparum Pf parasite GAP was produced and shown to generate aseptic Pf sporozoites SPZ that invade hepatocytes but do not replicate We will use this genetically attenuated double mutant parasite deficient in the genes encoding SLARP and B Pf slarp b GAP to manufacture characterize and release a corresponding PfSPZ Vaccine PfSPZ slarp b Vaccine also known as PfSPZ GA Vaccine in compliance with current Good Manufacturing Practices cGMPs conduct pre clinical Investigational New Drug application IND enabling studies develop a protocol for a phase clinical trial and submit an IND to the FDA The work is based on a wealth of literature describing the robust protective immunity that can be induced in humans immunized with PfSPZ that invade hepatocytes but arrest during liver stage development Sanariaandapos s PfSPZ Vaccine consisting of radiation attenuated aseptic purified cryopreserved PfSPZ protected of volunteers who received the highest dose of PfSPZ administered in the recent phase clinical trial The PfSPZ Vaccine is now being further assessed in clinical trials in the U S and Mali with additional trials pending soon in Tanzania Germany and Equatorial Guinea and is on an accelerated development program leading to licensure in years for elimination campaigns in Africa and prevention of malaria in travelers However there would be manufacturing advantages and potential potency and regulatory advantages leading to significant cost of goods COG savings if the radiation attenuated parasites were replaced with GAPs We have demonstrated that eliminating the slarp and b genes leads to attenuation similar to radiation and that in rodent malarias slarp b SPZs elicit excellent protective immunity against SPZ challenge and do not lead to blood stage infection All prior Pf GAPs showed leaky attenuation and breakthrough liver stage development in vivo or in vitro To overcome this critical problem our previous Phase II SBIR involved Pf strain engineering phenotypic characterization and proof of concept production of PfSPZ bearing knockout KO lesions in two attenuating genes double KO strains that would express a tight attenuated phenotype with no breakthroughs and yet possess robust characteristics suited for our manufacturing process A number of knock out parasites were produced and assessed but only the slarp and b deficient clone of Pf met all of our requirements for moving forward in development PfSPZ produced from the slarp and b deficient clone of Pf were completely attenuated at the early liver stage with no breakthroughs A Master Cell Bank of this clone was made and an engineering production run was performed to demonstrate that the Pf slarp b GAP was suitable for producing aseptic purified cryopreserved PfSPZ This was successfully accomplished We now propose to initiate full pre clinical development and IND submission in preparation for a phase clinical trial of PfSPZ slarp b Vaccine PUBLIC HEALTH RELEVANCE Malaria afflicts hundreds of millions of people killing over individuals each year A powerful tool is needed for eliminating Plasmodium falciparum malaria from defined geographical areas Ideally this would be a highly effective long acting vaccine that prevents disease and parasite transmission This proposal describes a project to manufacture a genetically attenuated form of P falciparum engineered to completely arrest development in liver stages as the basis for a next generation whole sporozoite malaria vaccine that is ready for clinical testing