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Ishizuka, Andrew S; Lyke, Kirsten E; DeZure, Adam; Berry, Andrea A; Richie, Thomas L; Mendoza, Floreliz H; Enama, Mary E; Gordon, Ingelise J; Chang, Lee-Jah; Sarwar, Uzma N; Zephir, Kathryn L; Holman, LaSonji A; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Chakravarty, Sumana; Manoj, Anita; Li, MingLin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; K C, Natasha; Murshedkar, Tooba; DeCederfelt, Hope; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Saunders, Jamie G; Laurens, Matthew B; Plowe, Christopher V; Flynn, Barbara; Whalen, William R; Todd, J P; Noor, Jay; Rao, Srinivas; Sierra-Davidson, Kailan; Lynn, Geoffrey M; Epstein, Judith E; Kemp, Margaret A; Fahle, Gary A; Mikolajczak, Sebastian A; Fishbaugher, Matthew; Sack, Brandon K; Kappe, Stefan H I; Davidson, Silas A; Garver, Lindsey S; Björkström, Niklas K; Nason, Martha C; Graham, Barney S; Roederer, Mario; Sim, B Kim Lee; Hoffman, Stephen L; Ledgerwood, Julie E; Seder, Robert A
Nature medicine, 06/2016, Letnik: 22, Številka: 6Journal Article
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.
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in: SICRIS
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