| Literature DB >> 27158907 |
Andrew S Ishizuka1, Kirsten E Lyke2, Adam DeZure1, Andrea A Berry2, Thomas L Richie3, Floreliz H Mendoza1, Mary E Enama1, Ingelise J Gordon1, Lee-Jah Chang1, Uzma N Sarwar1, Kathryn L Zephir1, LaSonji A Holman1, Eric R James3, Peter F Billingsley3, Anusha Gunasekera3, Sumana Chakravarty3, Anita Manoj3, MingLin Li3,4, Adam J Ruben3, Tao Li3, Abraham G Eappen3, Richard E Stafford3,4, Natasha K C3,4, Tooba Murshedkar3, Hope DeCederfelt5, Sarah H Plummer1, Cynthia S Hendel1, Laura Novik1, Pamela J M Costner1, Jamie G Saunders1, Matthew B Laurens2, Christopher V Plowe2, Barbara Flynn1, William R Whalen1, J P Todd1, Jay Noor1, Srinivas Rao1, Kailan Sierra-Davidson1, Geoffrey M Lynn1, Judith E Epstein6, Margaret A Kemp7, Gary A Fahle7, Sebastian A Mikolajczak8, Matthew Fishbaugher8, Brandon K Sack8, Stefan H I Kappe8, Silas A Davidson9, Lindsey S Garver9, Niklas K Björkström10, Martha C Nason11, Barney S Graham1, Mario Roederer1, B Kim Lee Sim3,4, Stephen L Hoffman3, Julie E Ledgerwood1, Robert A Seder1.
Abstract
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.Entities:
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Year: 2016 PMID： 27158907 DOI： 10.1038/nm.4110
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440