Published May 9, 2016
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Protection against malaria at 1 year and immune correlates following PfSPZ vaccination
Creators
- 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.
Description
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 × 105 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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