title: Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children.
abstract: BACKGROUND
  This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.
  
  
  METHODS
  The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.
  
  
  RESULTS
  No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).
  
  
  CONCLUSIONS
  These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00513669.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Patrick Georges
authors.initials: PG
authors.lastname: Cech
authors.forename: Thomas
authors.initials: T
authors.lastname: Aebi
authors.forename: Mwanajaa Shomari
authors.initials: MS
authors.lastname: Abdallah
authors.forename: Maxmillian
authors.initials: M
authors.lastname: Mpina
authors.forename: Ester Barnabas
authors.initials: EB
authors.lastname: Machunda
authors.forename: Nicole
authors.initials: N
authors.lastname: Westerfeld
authors.forename: Sabine Alexandra
authors.initials: SA
authors.lastname: Stoffel
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Zurbriggen
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.forename: Marcel
authors.initials: M
authors.lastname: Tanner
authors.forename: Claudia
authors.initials: C
authors.lastname: Daubenberger
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry*; D008875:Middle Aged; D057786:Peptidomimetics / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry*; D022701:Virosomes; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D057786:Peptidomimetics; D015800:Protozoan Proteins; D022701:Virosomes; C090077:apical membrane antigen I, Plasmodium; C041595:circumsporozoite protein, Protozoan