We are using controlled human malaria infection (CHMI) by direct venous 
inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf) 
sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of 
developing PfSPZ Vaccine to prevent malaria in Africa. Immunization with five 
doses at 0, 4, 8, 12, and 20 weeks of 2.7 × 105 PfSPZ of PfSPZ Vaccine gave 65% 
vaccine efficacy (VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 
52% (time to event) or 29% (proportional) VE over 24 weeks against naturally 
transmitted Pf in Malian adults. We assessed the identical regimen in Tanzanians 
for VE against PfSPZ Challenge. Twenty- to thirty-year-old men were randomized 
to receive five doses normal saline or PfSPZ Vaccine in a double-blind trial. 
Vaccine efficacy was assessed 3 and 24 weeks later. Adverse events were similar 
in vaccinees and controls. Antibody responses to Pf circumsporozoite protein 
were significantly lower than in malaria-naïve Americans, but significantly 
higher than in Malians. All 18 controls developed Pf parasitemia after CHMI. 
Four of 20 (20%) vaccinees remained uninfected after 3 week CHMI (P = 0.015 by 
time to event, P = 0.543 by proportional analysis) and all four (100%) were 
uninfected after repeat 24 week CHMI (P = 0.005 by proportional, P = 0.004 by 
time to event analysis). Plasmodium falciparum SPZ Vaccine was safe, well 
tolerated, and induced durable VE in four subjects. Controlled human malaria 
infection by DVI of PfSPZ Challenge appeared more stringent over 24 weeks than 
mosquito bite CHMI in United States or natural exposure in Malian adults, 
thereby providing a rigorous test of VE in Africa.