Protection against malaria at 1 year and immune correlates following PfSPZ vaccination

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

Research output: Contribution to journalArticle

128 Scopus citations

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-I 3-producing CD8 T cells were present at â 1/4100-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.

Original languageEnglish (US)
Pages (from-to)614-623
Number of pages10
JournalNature Medicine
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ishizuka, A. S., Lyke, K. E., DeZure, A., Berry, A. A., Richie, T. L., Mendoza, F. H., Enama, M. E., Gordon, I. J., Chang, L. J., Sarwar, U. N., Zephir, K. L., Holman, L. A., James, E. R., Billingsley, P. F., Gunasekera, A., Chakravarty, S., Manoj, A., Li, M., Ruben, A. J., ... Seder, R. A. (2016). Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nature Medicine, 22(6), 614-623. https://doi.org/10.1038/nm.4110