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A field trial to assess a blood-stage malaria vaccine.

2011 Sep 15

Journal Article

Thera, M.A.; Doumbo, O.K.; Coulibaly, D.; Laurens, M.B.; Ouattara, A.; Kone, A.K.; Guindo, A.B.; Traore, K.; Traore, I.; Kouriba, B.; Diallo, D.A.; Diarra, I.; Daou, M.; Dolo, A.; Tolo, Y.; Sissoko, M.S.; Niangaly, A.; Sissoko, M.; Takala-Harrison, S.; Lyke, K.E.; Wu, Y.; Blackwelder, W.C.; Godeaux, O.; Vekemans, J.; Dubois, M.C.; Ballou, R.; Cohen, J.; Thompson, D.; Dube, T.; Soisson, L.; Diggs, C.L.; House, B.; Lanar, D.E.; Dutta, S.; Heppner, G.; Plowe, C.V.

N Engl J Med






Antibodies, Protozoan; Antigens, Protozoan; Child, Preschool; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Malaria Vaccines; Malaria, Falciparum; Male; Plasmodium falciparum; Proportional Hazards Models; Rabies Vaccines

BACKGROUND: Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), 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. (Funded by the National Institute of Allergy and Infectious Diseases and others; number, NCT00460525.).

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