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

Description

DESCRIPTION provided by applicant This proposal will demonstrate proof of concept for a whole parasite WP vaccine directed against Plasmodium falciparum Pf sexual and mosquito stages SMS that will be used alone or in combination with PfSPZ Vaccine for interrupting malaria transmission VIMT from the human host to the mosquito vector Such a PfSMS WP VIMT will be an ideal complement to the PfSPZ Vaccine which has shown complete protection against parasite infection in recent clinical trials If the PfSPZ Vaccine prevents infection and transmission in of recipients and PfSMS WP VIMT prevents transmission in of recipients the combination will prevent transmission in at least of recipients The PfSMS WP VIMT offers major advantages to a subunit PfSMS vaccine based on one or a few antigens This vaccine approach will increase the chance that more individuals will have protective immune responses and reduce the possibility of the parasites being able to select for evasion of immune responses by dramatically increasing the number of immunogens against which protective antibodies are induced When used in combination with PfSPZ Vaccine PfSMS WP VIMT will prevent transmission of parasites that may be selected for resistance to PfSPZ Vaccine Sanaria uniquely produces Pf gametocytes sexual stages under GMP conditions and now consistently produces a mixture of gametes zygotes and ookinetes enriched for ookinetes in vitro We partially purified these parasites immunized mice with the preparation in adjuvant and showed that the sera from the immunized mice completely inhibited transmission of parasites to mosquitoes We will exploit Sanariaandapos s unique expertise in GMP compliant gametocyte production and in vitro PfSPZ production as well as extensive experience in parasite purification and in vivo transmission blocking feeding assays to develop produce and test PfSMS WP VIMT We will produce cultures of PfSMS from three time points min h and h to ensure that all PfSMS stages are present We will purify PfSMS in these cultures away from RBCs to obtain purified vaccine preparations Proof of concept will be demonstrated by immunizing mice with the PfSMS WP preparations in combination with adjuvants then testing for antibody responses against cultured parasites and known PfSMS antigens and for transmission blocking activity in an in vivo standard membrane feeding assay The lead candidates will be further tested in mice for interactions with the PfSPZ Vaccine after co administration by direct venous inoculation DVI In Phase II we will finalize methods for scaled up manufacturing in compliance with cGMPs and quality control QC release and stability assays manufacture in compliance with cGMPs conduct QC release assays initiate QC stability studies conduct pre clinical toxicology studies design a clinical trial and prepare al information for an Investigational New Drug application IND PUBLIC HEALTH RELEVANCE Malaria remains the most important parasitic disease affecting mankind There are over deaths per year due to malaria most of these deaths are in children under years old Over million infections occur each year worldwide Success in this project will be a major step towards developing a whole parasite vaccine that will prevent transmission of malaria from human hosts to mosquitoes which if used in combination with Sanariaandapos s highly protective PfSPZ Vaccine will be the ideal tool for malaria elimination