title: A field trial to assess a blood-stage malaria vaccine.
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.).
authors.affiliation: Malaria Research and Training Center, University of Bamako, Bamako, Mali.
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Drissa
authors.initials: D
authors.lastname: Coulibaly
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Laurens
authors.forename: Amed
authors.initials: A
authors.lastname: Ouattara
authors.forename: Abdoulaye K
authors.initials: AK
authors.lastname: Kone
authors.forename: Ando B
authors.initials: AB
authors.lastname: Guindo
authors.forename: Karim
authors.initials: K
authors.lastname: Traore
authors.forename: Idrissa
authors.initials: I
authors.lastname: Traore
authors.forename: Bourema
authors.initials: B
authors.lastname: Kouriba
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Issa
authors.initials: I
authors.lastname: Diarra
authors.forename: Modibo
authors.initials: M
authors.lastname: Daou
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Youssouf
authors.initials: Y
authors.lastname: Tolo
authors.forename: Mahamadou S
authors.initials: MS
authors.lastname: Sissoko
authors.forename: Amadou
authors.initials: A
authors.lastname: Niangaly
authors.forename: Mady
authors.initials: M
authors.lastname: Sissoko
authors.forename: Shannon
authors.initials: S
authors.lastname: Takala-Harrison
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Olivier
authors.initials: O
authors.lastname: Godeaux
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Darby
authors.initials: D
authors.lastname: Thompson
authors.forename: Tina
authors.initials: T
authors.lastname: Dube
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Brent
authors.initials: B
authors.lastname: House
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D016016:Proportional Hazards Models; D011819:Rabies Vaccines
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D011819:Rabies Vaccines