title: Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Alhydrogel, Montanide ISA 720 or AS02.
abstract: BACKGROUND
  Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies.
  
  
  RESULTS
  We assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 microg and 50 microg doses with three different adjuvants, Alhydrogel, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8-10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80-100%). Induration occurred in the Montanide 50 microg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1-2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNgamma and IL-5 cytokines.
  
  
  CONCLUSIONS
  All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies.
  
  
  BACKGROUND
  (Clinicaltrials.gov) NCT00730782.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. M.Roestenberg@mmb.umcn.nl
authors.forename: Meta
authors.initials: M
authors.lastname: Roestenberg
authors.forename: Ed
authors.initials: E
authors.lastname: Remarque
authors.forename: Erik
authors.initials: E
authors.lastname: de Jonge
authors.forename: Rob
authors.initials: R
authors.lastname: Hermsen
authors.forename: Hildur
authors.initials: H
authors.lastname: Blythman
authors.forename: Odile
authors.initials: O
authors.lastname: Leroy
authors.forename: Egeruan
authors.initials: E
authors.lastname: Imoukhuede
authors.forename: Soren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Bart
authors.initials: B
authors.lastname: Faber
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.forename: Miranda
authors.initials: M
authors.lastname: Arnold
authors.forename: Vanessa
authors.initials: V
authors.lastname: Walraven
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Quirijn
authors.initials: Q
authors.lastname: de Mast
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ascarateil
authors.forename: Andre
authors.initials: A
authors.lastname: van der Ven
authors.forename: Alan
authors.initials: A
authors.lastname: Thomas
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D016778:Malaria, Falciparum / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D008875:Middle Aged; D009829:Oleic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D010963:Plasmodium falciparum / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D017780:Malaria Vaccines; D009829:Oleic Acids; D014614:Vaccines, Synthetic; C001681:mannide monooleate; D008353:Mannitol; D000536:Aluminum Hydroxide