A field trial to assess a blood-stage malaria vaccine.
2011 Sep 15
Journal Article
Authors:
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.
Secondary:
N Engl J Med
Volume:
365
Pagination:
1004-13
Issue:
11
PMID:
21916638
Keywords:
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
Abstract:
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; ClinicalTrials.gov number, NCT00460525.).
