Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, 
purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, 
cryopreserved PfSPZ administered to subjects taking weekly chloroquine 
chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous 
controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium 
falciparum sporozoite-CVac has never been assessed against CHMI in African 
vaccinees. We assessed the safety, immunogenicity, and VE against homologous 
CHMI of three doses of 2.7 × 106 PfSPZ of PfSPZ Vaccine at 8-week intervals and 
three doses of 1.0 × 105 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm 
randomized, double-blind, placebo-controlled, and conducted in parallel. There 
were no differences in solicited adverse events between vaccinees and normal 
saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 
days after administration of investigational product. However, from days 7-13, 
PfSPZ-CVac recipients had significantly more AEs, probably because of Pf 
parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine 
recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a 
median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and 
at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 
0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose 
was likely a result of later stage parasite maturation in the liver, leading to 
induction of cellular immunity against a greater quantity and broader array of 
antigens.