title: Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.
abstract: BACKGROUND
  The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.
  
  
  RESULTS
  A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.
  
  
  CONCLUSIONS
  The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.
authors.affiliation: Malaria Research and Training Center, University of Bamako, Bamako, Mali.
authors.forename: Mahamadou A
authors.initials: MA
authors.lastname: Thera
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Drissa
authors.initials: D
authors.lastname: Coulibaly
authors.forename: Dapa A
authors.initials: DA
authors.lastname: Diallo
authors.forename: Abdoulaye K
authors.initials: AK
authors.lastname: Kone
authors.forename: Ando B
authors.initials: AB
authors.lastname: Guindo
authors.forename: Karim
authors.initials: K
authors.lastname: Traore
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Mahamadou S
authors.initials: MS
authors.lastname: Sissoko
authors.forename: Mounirou
authors.initials: M
authors.lastname: Baby
authors.forename: Mady
authors.initials: M
authors.lastname: Sissoko
authors.forename: Issa
authors.initials: I
authors.lastname: Diarra
authors.forename: Amadou
authors.initials: A
authors.lastname: Niangaly
authors.forename: Amagana
authors.initials: A
authors.lastname: Dolo
authors.forename: Modibo
authors.initials: M
authors.lastname: Daou
authors.forename: Sory I
authors.initials: SI
authors.lastname: Diawara
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: V Ann
authors.initials: VA
authors.lastname: Stewart
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Elke S
authors.initials: ES
authors.lastname: Bergmann-Leitner
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Alex
authors.initials: A
authors.lastname: Owusu
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Jason N
authors.initials: JN
authors.lastname: Nixon
authors.forename: Aric
authors.initials: A
authors.lastname: Gregson
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Takala
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D016778:Malaria, Falciparum / Q000517:prevention & control; D008297:Male; D008302:Mali; D008565:Membrane Proteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium