title: Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians.
abstract: BACKGROUND
  Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses.
  
  
  RESULTS
  A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels.
  
  
  CONCLUSIONS
  Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00343005.
authors.affiliation: Malaria Research and Training Center, Department of Hematology, University of Bamako, Bamako, Mali.
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: David J
authors.initials: DJ
authors.lastname: Diemert
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Moussa
authors.initials: M
authors.lastname: Sogoba
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Niambele
authors.forename: Mahamadoun H
authors.initials: MH
authors.lastname: Assadou
authors.forename: Ousmane
authors.initials: O
authors.lastname: Guindo
authors.forename: Beh
authors.initials: B
authors.lastname: Kamate
authors.forename: Mounirou
authors.initials: M
authors.lastname: Baby
authors.forename: Mady
authors.initials: M
authors.lastname: Sissoko
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Malkin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Mullen
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Ogobara
authors.initials: O
authors.lastname: Doumbo
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry*; D015331:Cohort Studies; D004311:Double-Blind Method; D006801:Humans; D017780:Malaria Vaccines / Q000737:chemistry*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008302:Mali; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D011994:Recombinant Proteins