Universal Attenuated Sporozoite Vaccine and Challenge System

Period of Performance: 06/15/2016 - 05/31/2017

$989K

Phase 2 SBIR

Recipient Firm

Sanaria, Inc.
Rockville, MD 20850
Principal Investigator

Abstract

ABSTRACTSanaria?s Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines development program is receiving globalsupport. Trials of PfSPZ Vaccine (radiation attenuated PfSPZ) or PfSPZ-CVac (PfSPZ ChemoprophylaxisVaccine) administered by direct venous inoculation (DVI), including ~1,500 adults to infants were initiated inDecember 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, as100% protective efficacy at 9 weeks after last dose has been established with a 3-dose regimen. Protectiveefficacy has been shown to be durable against controlled malaria infection (CHMI) for at least a year, andagainst intense natural transmission in Mali of heterogeneous strains of Pf for at least 6 months. PfSPZVaccine and PfSPZ-CVac are comprised of PfSPZ of the NF54 strain of Pf. Short-term protection (3 weeks) byPfSPZ 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 willbroaden and strengthen the protective immune responses against shared dominant and sub-dominantepitopes. All of the trials described above utilize this approach. The 2nd and potentially more efficient approachwill be to combine PfSPZ from different strains of Pf in the same vaccine. Our analysis of genomic sequencedata, predicted proteomes, and predicted T cell epitopes indicates that using two strains of Pf should besufficient. This project fills an important gap. We have funding from VRC, NIAID, NIH to conduct a clinical trialof a multivalent PfSPZ vaccine, but require the funds to manufacture, characterize, and release the multi-valentvaccine, and to navigate the regulatory/clinical affairs pathways required to initiate the trial. In this Phase IIBSBIR project, we propose to, 1) Manufacture and QC release chloroquine sensitive PfSPZ Challenge of a WAfrican 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) andPfSPZ Challenge (NF54) for a two-strain combination PfSPZ-CVac; and 4) Conduct an end of phase 2 meetingwith 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. Successwill reduce the time to licensure of a PfSPZ vaccine for travelers/military by at least a year and save > $50M. Itwill also facilitate more rapid development of all pre-erythrocytic stage vaccines intended to provide the highlevel (>80%) protection required for a vaccine for travelers, military, and elimination campaigns.