title: Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children.
abstract: BACKGROUND
  Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area.
  
  
  METHODS
  This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript.
  
  
  RESULTS
  Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine.
  
  
  CONCLUSIONS
  AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00341250.
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali.
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Ousmane
authors.initials: O
authors.lastname: Guindo
authors.forename: Beh
authors.initials: B
authors.lastname: Kamate
authors.forename: Moussa
authors.initials: M
authors.lastname: Sogoba
authors.forename: Mohamed Balla
authors.initials: MB
authors.lastname: Niambelé
authors.forename: Mady
authors.initials: M
authors.lastname: Sissoko
authors.forename: Mounirou
authors.initials: M
authors.lastname: Baby
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Mark
authors.initials: M
authors.lastname: Pierce
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000536:Aluminum Hydroxide; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology / Q000627:therapeutic use*; D002675:Child, Preschool; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008302:Mali; D008565:Membrane Proteins / Q000276:immunology / Q000627:therapeutic use*; D015800:Protozoan Proteins / Q000276:immunology / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D000536:Aluminum Hydroxide