Dose Escalating and Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) in Healthy African Adults in Mali

Brief Summary

Detailed Description

It is known that humans can be protected against malaria by repeated immunization with radiation attenuated sporozoites. Traditionally, those sporozoites are administered by exposing the vaccinee to at least 1000 bites of sporozoite infected irradiated mosquitoes, an approach that is unsuitable for mass vaccination campaigns. Recently, Sanaria, Inc. developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation attenuated cryopreserved sporozoites from a well characterized isolate of P. falciparum (Hoffman et al., 2010). This product, which is called PfSPZ Vaccine, can be administered by needle and syringe. Previous studies conducted by the Vaccine Research Center and the Navy have established that IV administration of PfSPZ Vaccine can induce sterile protection against controlled human malaria infection (CHMI) with a homologous strain of P. falciparum in up to 100% of malaria na(SqrRoot) ve individuals (Seder et al., 2013). A recent study conducted as collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. (Sissoko et al., unpublished) has shown that sterile protection against naturally occurring malaria infection can be achieved, but not at the level seen in the US nor at the level desired. The next logical step in an attempt to improve protective efficacy in the targeted endemic population is to increase the PfSPZ Vaccine dose, increasing the interval between the first and second doses to 8 weeks (as was done in WRAIR 2080 in the group receiving 3 doses of 4.5x105 PfSPZ), and reducing the numbers of doses to three. Additionally, in this study design, we also can begin to understand how the standard controlled human malaria infection (CHMI) model may be used in the field and start to explore the impact of such factors as malaria co infection and drug treatment have on vaccine responses. The initial dose escalation pilot study will focus on safety and tolerability of the PfSPZ Vaccine. A defined number of subjects enrolled during the pilot study will also undergo further evaluation, including randomization to receive or not receive drug treatment immediately prior to each vaccination and examination of protective efficacy against homologous CHMI via PfSPZ Challenge. The targeted dose (18x105 PfSPZ Vaccine), if safe and tolerable, will be administered to a larger cohort in a double blind, randomized, placebo controlled trial to examine the protective efficacy of the vaccine against naturally occurring infection. PfSPZ Vaccinees (Arm 2) from the main study will be re enrolled the following malaria transmission along with age, sex, and village matched controls (re enrolled Arm 3, additional controls) to explore the duration of protection through another malaria transmission season. Subjects will be recruited from rural villages in Mali. The study will be conducted as collaboration among MRTC, LMIV/NIAID, and Sanaria, Inc.

Primary Outcomes

Secondary Outcomes

• Protective Efficacy (pilot phase)(Immediately following PfSPZ CHMI)
• Protective Efficacy (main phase)(Immediately following 3rd vaccination)