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Sanaria® PfSPZ Vaccine is composed of aseptic, purified, cryopreserved, attenuated (non-replicating), metabolically active Plasmodium falciparum (Pf ) sporozoites (SPZ) produced in compliance with good manufacturing practices (GMPs) that meet all regulatory standards. This vaccine provided full protection against Pf infection in 100% (6/6) volunteers, who received five doses of 1.35 × 105 PfSPZ administered intravenously in a study at the Vaccine Research Center (VRC), NIAID, NIH [1]. Based on these data, the PfSPZ Vaccine Clinical Consortium composed of investigators from USA, Africa, and Europe has developed a four stage clinical development plan (CDP) that maps out a 4-5 year timeline to licensure and a large scale demonstration project to eliminate malaria from an island population in Africa. In 2014, six different clinical trials of PfSPZ Vaccine at seven clinical sites in the United States (Bethesda, Baltimore, Silver Spring), Mali, Tanzania, Equatorial Guinea, and Germany will be underway. These six clinical trials, which include >450 subjects, comprise Stage 1 of the four stage PfSPZ Vaccine CDP. They are designed to 1) assess the reproducibility of the data generated in the VRC study and 2) assess and optimize durability of protection, protection against heterologous strains of Pf, reduction in numbers of doses, immune assays that predict protection, implementation of immunization, and alternative route of administration. We will provide an update of these stage 1 clinical trials and plans for stage 2 studies that will address questions required for progressing to pivotal phase 3 clinical trials in stage 3, and to demonstration projects for focal elimination in small populations.

Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum (Pf), until recently have been performed primarily by using Pf-infected Anopheles stephensi mosquitoes to bite human subjects. This approach has proven highly successful for studies of drugs and vaccines. However, its use has been limited to the few clinical centers, which have access to Pf-infected mosquitoes. Sanaria Inc. has established a new CHMI methodology whereby aseptic, purified, cryopreserved, infectious sporozoites (SPZ) of Pf are used to infect volunteers when administered by needle and syringe. This product is known as PfSPZ Challenge. Here we summarize the results of seven clinical trials in the Netherlands, UK, Tanzania, USA, Germany, Spain, and Kenya including 178 subjects. Four of the trials were done in countries where CHMI had never been done before. These trials assessed intradermal, intramuscular and intravenous administration of varying doses of PfSPZ Challenge. The three primary goals of 100% infection rates, a prepatent period comparable to the bite of five Pf-infected mosquitoes (11 to 11.5 days) and a dose response have been met by intravenous and intramuscular administration. PfSPZ Challenge opens up the potential for CHMI to be done in any research facility set up for clinical malaria studies (see presentation by Sheehy et al.), including sites to which transport of A. stephensi is difficult or impossible (i.e. any site in Africa). The results of all the studies will be presented.

Background Mortality of severe malaria is significantly lower in patients treated with parenteral artesunate when compared to quinine. No significant side effects have been described from previous studies but follow-up periods have been limited. First reports from Europe have shown cases of posttreatment haemolysis occurring two weeks after the first dose of parenteral artesunate. Furthermore, haemolysis was accompanied by a delay in adequate reticulocytopoiesis for up to two weeks. All patients developing posttreatment haemolysis had hyperparasitaemia. The aim of this study was to gain information about the incidence, clinical impact and pathophysiological background of this effect in the hyperendemic setting of sub-Saharan Africa.