A Field Trial to Assess a Blood-Stage Malaria Vaccine

作者：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

来源：New England Journal of Medicine, 2011, 365(11): 1004-1013.

DOI：10.1056/nejmoa1008115

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.)

• 出版日期2011-9-15