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: Mahamadou A Thera, Ogobara K Doumbo, Drissa Coulibaly, Matthew B Laurens, Amed Ouattara, Abdoulaye K Kone, Ando B Guindo, Karim Traore, Idrissa Traore, Bourema Kouriba, Dapa A Diallo, Issa Diarra, Modibo Daou, Amagana Dolo, Youssouf Tolo, Mahamadou S Sissoko, Amadou Niangaly, Mady Sissoko, Shannon Takala-Harrison, Kirsten E Lyke, Yukun Wu, William C Blackwelder, Olivier Godeaux, Johan Vekemans, Marie-Claude Dubois, W Ripley Ballou, Joe Cohen, Darby Thompson, Tina Dube, Lorraine Soisson, Carter L Diggs, Brent House, David E Lanar, Sheetij Dutta, D Gray Heppner Jr, Christopher V Plowe
• Journal: The New England journal of medicine (N Engl J Med) Vol. 365 Issue 11 Pg. 1004-13 (Sep 15 2011) ISSN: 1533-4406 [Electronic] United States
• PMID: 21916638 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Malaria Vaccines
• Rabies Vaccines

Topics

• Antibodies, Protozoan (blood)
• Antigens, Protozoan (immunology)
• Child, Preschool
• Double-Blind Method
• Female
• Humans
• Kaplan-Meier Estimate
• Malaria Vaccines (adverse effects, immunology)
• Malaria, Falciparum (parasitology, prevention & control)
• Male
• Plasmodium falciparum (immunology, isolation & purification)
• Proportional Hazards Models
• Rabies Vaccines