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An effective malaria vaccine would improve the prospects for eradicating malaria.1 Vaccines that interrupt the transmission of malaria are emphasized in discussions of eradication,2 but the ideal malaria vaccine would provide a direct clinical benefit. Vaccines targeting the blood stages of malaria are intended to reduce morbidity and mortality and are being developed in hopes of creating a multistage, multiantigen vaccine.3
Vaccines based on two polymorphic Plasmodium falciparum blood-stage proteins, merozoite surface protein 14 and apical membrane antigen 1 (AMA1),5 were not shown to be effective in recent studies, probably because of insufficient cross-protection against diverse malaria strains6,7 or insufficient immunogenicity. A vaccine based on three non-AMA1 blood-stage antigens failed to prevent clinical malaria but reduced the risk of infections with vaccine-type strains.8 No such strain specificity was seen with a vaccine based on a pre-erythrocytic protein that prevents clinical malaria.9–11
FMP2.1/AS02A is a monovalent blood-stage malaria vaccine based on AMA1 from the 3D7 strain of P. falciparum.12 It had acceptable safety and tolerability in volunteers in the United States with no history of malaria13,14 and in malaria-exposed adults15 and children16 in Mali. In all these populations, FMP2.1/AS02A produced higher and more sustained antibody responses than a bivalent AMA1 vaccine that showed neither overall5 nor strain-specific17 efficacy in a recent trial in Mali. We conducted a proof-of-concept trial to assess the efficacy of FMP2.1/AS02A against clinical falciparum malaria in Malian children and to determine whether the efficacy was strain-specific.
Methods
Study Design
We conducted a randomized, controlled, double-blind trial. The protocol (available with the full text of this article at NEJM.org) was approved by the institutional review boards at the University of Bamako Faculty of Medicine, the University of Maryland, Baltimore, the Walter Reed Army Institute of Research, and the U.S. Army Surgeon General. The National Institute of Allergy and Infectious Diseases and the U.S. Agency for International Development reviewed the study protocol. The trial was monitored by the National Institute of Allergy and Infectious Diseases and the U.S. Army Medical Material Development Activity. An independent data and safety monitoring board and a local safety monitor were appointed by the National...