BACKGROUND Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine.

Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 g) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naïve subjects.The morbidity and mortality associated with malaria continue to exact a heavy price on many developing nations. The World Health Organization (WHO) estimates that 3.3 billion individuals live in areas where malaria is endemic, with 247 million cases and a million deaths reported for the year 2006 (41). In 1998, the Roll Back Malaria Partnership was launched to coordinate international malaria containment efforts and included the wide dissemination of long-lasting insecticidal nets, artemisinin-based combination therapy, indoor residual spraying of insecticide, and intermittent preventive treatment in pregnancy. In 2006, the success of implementing these interventions was variable, with some countries reporting a 50% decrease in the number of malaria cases and other countries reporting stable levels of transmission (5,8,13,41).Some pieces missing from the available armamentarium to fight malaria are safe and effective vaccines. Plasmodium falciparum is the species associated with the greatest morbidity and mortality. The approach to the development of a P. falciparum vaccine has paralleled the multistage nature of P. falciparum infections: preerythrocytic vaccines target the sporozoite or its antigens to achieve protection from infection; erythrocytic vaccines target the merozoite antigens to achieve protection from severe disease; and transmission-blocking vaccines utilize the gametocyte, zygote, or ookinete antigens to prevent sporogenic development in the vector (4,11,15,16,34,35,40). A multicomponent or multistage vaccine has also been proposed as a solution to the heterogeneity of the host's immune response and the parasite antigens.One antigen of interest in the development of P. falciparum erythrocytic vaccines is the erythrocyte binding antigen 175 (EBA-175). EBA-175 was the first P. falciparum ligand identified to have a role in high-affinity binding of the merozoite to the host's red blood cells (RBCs) (1, 7). EBA-175 binds to the RBC glycophorin A sialic acid residues, and the interac...