Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine

20 September 2013 vol 341, issue 6152, pages 1313-1420

Perspective – Immunology
Pasteur Approach to a Malaria Vaccine May Take the Lead
Michael F. Good
+ Author Affiliations
Institute for Glycomics, Griffith University, Gold Coast 4222, Australia.
Malaria is an infectious disease that is responsible for more loss of young lives than any other health condition. Eighty percent of the cases and nearly 1 million deaths from malaria occur in Africa each year. Although mortality has decreased in recent years, more must be done to improve and save the lives of sufferers. On page 1359 of this issue, Seder et al. (1) report that an attenuated form of the causative parasite can be administered intravenously and provide protection against malaria, taking us a step closer to achieving the goal of an effective vaccine.

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, LaSonji A. Holman, Eric R. James, Peter F. Billingsley, Anusha Gunasekera, Adam Richman, Sumana Chakravarty, Anita Manoj, Soundarapandian Velmurugan, MingLin Li, Adam J. Ruben, Tao Li, Abraham G. Eappen, Richard E. Stafford, Sarah H. Plummer, Cynthia S. Hendel, Laura Novik, Pamela J. M. Costner, Floreliz H. Mendoza, Jamie G. Saunders, Martha C. Nason, Jason H. Richardson, 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, and the VRC 312 Study Team
Science 20 September 2013: 1359-1365.
Published online 8 August 2013 [DOI:10.1126/science.1241800]
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 wel-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.