This is a randomized, double-blind, placebo-controlled, Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults by direct venous inoculation (DVI) to determine safety, immunogenicity, and efficacy against controlled human malaria infection (CHMI).
The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double deletion of the genes encoding the Mei2 and LINUP proteins, both of which are required for transition from liver to blood stage malaria. As a result, mei2-/linup- parasites undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream. No blood stage parasites are produced, either asexual or sexual, and the parasite life cycle does not progress.
CHMI will be performed using PfSPZ Challenge (NF54), composed of PfSPZ that are genetically intact and fully infectious. Because PfSPZ-LARC2 vaccine is also based on the Pf strain NF54, CHMI using PfSPZ Challenge (NF54) is considered homologous to the vaccine. It will be performed 6 weeks after the single administration of PfSPZ-LARC2 Vaccine or normal saline placebo (with an option to shorten the interval to 4 weeks if logistical issues arise, such as a risk that CHMI follow-up will overlap with the rainy season).