title: A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.
abstract: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda.
  
  
  
  Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL.
  
  
  
  A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%).
  
  
  
  GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso.
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.affiliation: London School of Hygiene & Tropical Medicine, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Germany; Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon.
authors.forename: Ulysse Ateba
authors.initials: UA
authors.lastname: Ngoa
authors.affiliation: Makerere University College of Health Sciences, Uganda.
authors.forename: Fred
authors.initials: F
authors.lastname: Kironde
authors.affiliation: Navrongo Health Research Centre, Ghana.
authors.forename: Frank
authors.initials: F
authors.lastname: Atuguba
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso.
authors.forename: Alfred B
authors.initials: AB
authors.lastname: Tiono
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Germany; Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon.
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.affiliation: Makerere University College of Health Sciences, Uganda.
authors.forename: Mark
authors.initials: M
authors.lastname: Kaddumukasa
authors.affiliation: Navrongo Health Research Centre, Ghana.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bangre
authors.affiliation: London School of Hygiene & Tropical Medicine, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Flach
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.affiliation: Centre for Infectious Disease Research in Zambia, Zambia.
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.affiliation: Statens Serum Institut, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Germany; Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Statens Serum Institut, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: mth@ssi.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002050:Burkina Faso; D002675:Child, Preschool; D005260:Female; D005681:Gabon; D005869:Ghana; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014454:Uganda
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C000599052:GMZ2 vaccine; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C089133:merozoite surface protein 3, Plasmodium; C072492:glutamate-rich protein, Plasmodium; D000536:Aluminum Hydroxide
keywords: Antibody; Efficacy; GLURP; GMZ2; MSP3; Phase 2 clinical trial; Plasmodium falciparum; Vaccine