Sanaria?s Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines development program is receiving global support. Trials of PfSPZ Vaccine (radiation attenuated PfSPZ) or PfSPZ-CVac (PfSPZ Chemoprophylaxis Vaccine) administered by direct venous inoculation (DVI), including ~1,500 adults to infants were initiated in December 2015 (Tanzania, U.S.) or will be initiated in early 2016 in Mali, Kenya (~500 infants), Ghana, Equatorial Guinea, Germany and 3 additional U.S. sites. These trials will assess 3-, 2- or 1-dose regimens, as 100% protective efficacy at 9 weeks after last dose has been established with a 3-dose regimen. Protective efficacy has been shown to be durable against controlled malaria infection (CHMI) for at least a year, and against intense natural transmission in Mali of heterogeneous strains of Pf for at least 6 months. PfSPZ Vaccine and PfSPZ-CVac are comprised of PfSPZ of the NF54 strain of Pf. Short-term protection (3 weeks) by PfSPZ Vaccine against a heterologous (different from the vaccine strain) CHMI with Pf7G8 parasites was 80%, but despite a significant delay in onset of parasitemia, 6 month sterile protective efficacy was only 10%. Sanaria is taking two approaches to improving protective efficacy against heterologous/heterogeneous strains. The 1st is to increase the dose of PfSPZ (NF54) per immunization based on the hypothesis that this will broaden and strengthen the protective immune responses against shared dominant and sub-dominant epitopes. All of the trials described above utilize this approach. The 2nd and potentially more efficient approach will be to combine PfSPZ from different strains of Pf in the same vaccine. Our analysis of genomic sequence data, predicted proteomes, and predicted T cell epitopes indicates that using two strains of Pf should be sufficient. This project fills an important gap. We have funding from VRC, NIAID, NIH to conduct a clinical trial of a multivalent PfSPZ vaccine, but require the funds to manufacture, characterize, and release the multi-valent vaccine, and to navigate the regulatory/clinical affairs pathways required to initiate the trial. In this Phase IIB SBIR project, we propose to, 1) Manufacture and QC release chloroquine sensitive PfSPZ Challenge of a W African Pf clone (NF166) that can be used for CHMI studies and as a component of a multi-strain PfSPZ-CVac; 2) Manufacture and release PfSPZ Vaccine based on the Brazilian Pf clone (7G8) and PfSPZ Vaccine (NF54) for a two-strain/clone PfSPZ Vaccine combination; 3) Manufacture and release PfSPZ Challenge (7G8) and PfSPZ Challenge (NF54) for a two-strain combination PfSPZ-CVac; and 4) Conduct an end of phase 2 meeting with FDA to propose and finalize a plan for using phase 3 CHMI trials with PfSPZ Challenge (NF54, 7G8, NF135.C10, and NF166) to replace phase 3 field trials to establish protective efficacy of the vaccines. Success will reduce the time to licensure of a PfSPZ vaccine for travelers/military by at least a year and save > $50M. It will also facilitate more rapid development of all pre-erythrocytic stage vaccines intended to provide the high level (>80%) protection required for a vaccine for travelers, military, and elimination campaigns.
Since inception this SBIR has been focused on providing the foundation for moving to a multivalent approach to vaccination if needed, a multi-strain/clone approach to controlled human malaria infection with Sanaria?s Plasmodium falciparum (Pf) sporozoite (SPZ)-based products. In this new project we will develop an optimized 2-strain/clone vaccine and multi-strain/clone controlled human malaria infection system, and an optimized approach for a travelers/military vaccine for pivotal phase 3 trials that takes advantage of these key parasites, and thereby significantly reduces the time and cost to achieve vaccine licensure and commercial launch.
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