A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine 
(PfSPZ Vaccine), confers sterile protection against controlled human malaria 
infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the 
vaccine strain up to 14 mo after final vaccination. No injectable malaria 
vaccine has demonstrated long-term protection against CHMI using Pf parasites 
heterologous to the vaccine strain. Here, we conducted an open-label trial with 
PfSPZ Vaccine at a dose of 9.0 × 105 PfSPZ administered i.v. three times at 8-wk 
intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 
wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated 
volunteers remained without parasitemia compared with none of six nonvaccinated 
controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat 
CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five 
(83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of 
six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were 
detected in all vaccine recipients. Cytokine production by T cells from 
vaccinated subjects after in vitro stimulation with homologous (NF54) or 
heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific 
T-cell responses in the blood peaked after the first immunization and were not 
enhanced by subsequent immunizations. Collectively, these data suggest durable 
protection against homologous and heterologous Pf parasites can be achieved with 
PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be 
enhanced by additional alterations in the vaccine dose and number of 
immunizations.