Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine

Robert A. Seder, Lee Jah Chang, Mary E. Enama, Kathryn L. Zephir, Uzma N. Sarwar, Ingelise J. Gordon, La Sonji A. Holman, Eric R. James, Peter F. Billingsley, Anusha Gunasekera, Adam Richman, Sumana Chakravarty, Anita Manoj, Soundarapandian Velmurugan, Ming Lin Li, Adam J. Ruben, Tao Li, Abraham G. Eappen, Richard E. Stafford, Sarah H. PlummerCynthia S. Hendel, Laura Novik, Pamela J.M. Costner, Floreliz H. Mendoza, Jamie G. Saunders, Martha C. Nason, Jason H. Richardson, Jittawadee Murphy, Silas A. Davidson, Thomas L. Richie, Martha Sedegah, Awalludin Sutamihardja, Gary A. Fahle, Kirsten E. Lyke, Matthew B. Laurens, Mario Roederer, Kavita Tewari, Judith E. Epstein, B. Kim Lee Sim, Julie E. Ledgerwood, Barney S. Graham, Stephen L. Hoffman

Research output: Contribution to journalArticle

408 Scopus citations

Abstract

Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine - composed of attenuated, aseptic, purified, cryopreserved PfSPZ - was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

Original languageEnglish (US)
Pages (from-to)1359-1365
Number of pages7
JournalScience
Volume341
Issue number6152
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Seder, R. A., Chang, L. J., Enama, M. E., Zephir, K. L., Sarwar, U. N., Gordon, I. J., Holman, L. S. A., James, E. R., Billingsley, P. F., Gunasekera, A., Richman, A., Chakravarty, S., Manoj, A., Velmurugan, S., Li, M. L., Ruben, A. J., Li, T., Eappen, A. G., Stafford, R. E., ... Hoffman, S. L. (2013). Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science, 341(6152), 1359-1365. https://doi.org/10.1126/science.1241800