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

Publication Type
Journal Article
Year of Publication
Thera, Mahamadou A; Doumbo, Ogobara K; Coulibaly, Drissa; Laurens, Matthew B; Ouattara, Amed; Kone, Abdoulaye K; Guindo, Ando B; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E; Wu, Yukun; Blackwelder, William C; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W Ripley; Cohen, Joe; Thompson, Darby; Dube, Tina; Soisson, Lorraine; Diggs, Carter L; House, Brent; Lanar, David E; Dutta, Sheetij; Heppner, D Gray; Plowe, Christopher V
N Engl J Med
Date Published
2011 Sep 15
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; ClinicalTrials.gov number, NCT00460525.).