An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ 
Vaccine, is highly protective against controlled human malaria infection (CHMI) 
3 weeks after immunization, but the durability of protection is unknown. We 
assessed how vaccine dosage, regimen, and route of administration affected 
durable protection in malaria-naive adults. After four intravenous immunizations 
with 2.7 × 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without 
parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic 
subjects from this dosage group underwent repeat CHMI at 59 weeks, and none 
developed parasitemia. Although Pf-specific serum antibody levels correlated 
with protection up to 21-25 weeks after immunization, antibody levels waned 
substantially by 59 weeks. Pf-specific T cell responses also declined in blood 
by 59 weeks. To determine whether T cell responses in blood reflected responses 
in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific 
interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies 
in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred 
durable protection to malaria through long-lived tissue-resident T cells and 
that administration of higher doses may further enhance protection.