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

Open access
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·2016·Nature Medicine

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 × 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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Authors
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., Li, T., Eappen, A. G., Stafford, R. E., K C, N., Murshedkar, T., DeCederfelt, H., Plummer, S. H., Hendel, C. S., Novik, L., Costner, P. J. M., Saunders, J. G., Laurens, M. B., Plowe, C. V., Flynn, B., Whalen, W. R., Todd, J. P., Noor, J., Rao, S., Sierra-Davidson, K., Lynn, G. M., Epstein, J. E., Kemp, M. A., Fahle, G. A., Mikolajczak, S. A., Fishbaugher, M., Sack, B. K., Kappe, S. H. I., Davidson, S. A., Garver, L. S., Björkström, N. K., Nason, M. C., Graham, B. S., Roederer, M., Sim, B. K. L., Hoffman, S. L., Ledgerwood, J. E., & Seder, R. A.
Venue
Nature Medicine
Published
2016-05-09
Volume
22
Issue
6
Pages
614-623
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2346928357
Cited by
367
References
44
FWCI
46.55
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. https://app.cochat.ai/papers/10.1038/nm.4110
The paper
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. https://doi.org/10.1038/nm.4110

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.