Protection against malaria at 1 year and immune correlates following PfSPZ vaccination.
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.
Ishizuka, AS; Lyke, KE; DeZure, A; Berry, AA; Richie, TL; Mendoza, FH; Enama, ME; Gordon, IJ; Chang, L-J; Sarwar, UN; Zephir, KL; Holman, LA; James, ER; Billingsley, PF; Gunasekera, A; Chakravarty, S; Manoj, A; Li, M; Ruben, AJ; Li, T; Eappen, AG; Stafford, RE; K C, N; Murshedkar, T; DeCederfelt, H; Plummer, SH; Hendel, CS; Novik, L; Costner, PJM; Saunders, JG; Laurens, MB; Plowe, CV; Flynn, B; Whalen, WR; Todd, JP; Noor, J; Rao, S; Sierra-Davidson, K; Lynn, GM; Epstein, JE; Kemp, MA; Fahle, GA; Mikolajczak, SA; Fishbaugher, M; Sack, BK; Kappe, SHI; Davidson, SA; Garver, LS; Björkström, NK; Nason, MC; Graham, BS; Roederer, M; Sim, BKL; Hoffman, SL; Ledgerwood, JE; Seder, RA
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