PfSPZ-LARC2 Vaccine(Sanaria)

This is a first-in-humans randomized, double-blind, placebo-controlled Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults, children, and (optionally) infants by direct venous inoculation (DVI) to determine safety, tolerability, and immunogenicity. The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double genetic deletion, of the Mei2 and LINUP genes, and undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream (no blood stage parasites are produced). Because Pf parasites with the LARC phenotype replicate in the liver, they are expected to be a potent immunogen to induce anti-malarial immunity, similar to replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine). Because the parasites are also intrinsically attenuated, they are expected to be highly safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine and to the single-gene(Mei2)-deleted GA2 vaccine (also LARC phenotype) tested at the Leiden University Medical Center. The genetically attenuated PfSPZ-LARC2 Vaccine should thus combine the best-in-class efficacy of PfSPZ-CVac (chloroquine) with the excellent safety and tolerability of intrinsically attenuated PfSPZ Vaccine and GA2 vaccine.
This trial is designed to test the hypotheses that:
1. The vaccine is safe and well tolerated in each age groups.
2. The true rate of breakthrough blood stage infection (or other concerning adverse events) is less than about 5%, with an 95% confidence level (this will be the level of confidence that there are no breakthroughs if no breakthroughs occur in the 60 participants receiving PfSPZ-LARC2 Vaccine).