title: A randomized controlled phase Ib trial of the malaria vaccine candidate GMZ2 in African children.
abstract: BACKGROUND
  GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials.
  
  
  RESULTS
  Thirty children one to five years of age were randomized to receive three doses of either 30 µg or 100 µg of GMZ2, or rabies vaccine. GMZ2, adjuvanted in aluminum hydroxide, was administered on Days 0, 28 and 56. All participants received a full course of their respective vaccination and were followed up for one year. Both 30 µg and 100 µg GMZ2 vaccine doses were well tolerated and induced antibodies and memory B-cells against GMZ2 as well as its antigenic constituents MSP3 and GLURP. After three doses of vaccine, the geometric mean concentration of antibodies to GMZ2 was 19-fold (95%CI: 11,34) higher in the 30 µg GMZ2 group than in the rabies vaccine controls, and 16-fold (7,36) higher in the 100 µg GMZ2 group than the rabies group. Geometric mean concentration of antibodies to MSP3 was 2.7-fold (1.6,4.6) higher in the 30 µg group than in the rabies group and 3.8-fold (1.5,9.6) higher in the 100 µg group. Memory B-cells against GMZ2 developed in both GMZ2 vaccinated groups.
  
  
  CONCLUSIONS
  Both 30 µg as well as 100 µg intramuscular GMZ2 are immunogenic, well tolerated, and safe in young, malaria-exposed Gabonese children. This result confirms previous findings in naïve and malaria-exposed adults and supports further clinical development of GMZ2.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00703066.
authors.affiliation: Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bélard
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Aurore B
authors.initials: AB
authors.lastname: Hounkpatin
authors.forename: Frieder
authors.initials: F
authors.lastname: Schaumburg
authors.forename: Ulysse Ateba
authors.initials: UA
authors.lastname: Ngoa
authors.forename: Meral
authors.initials: M
authors.lastname: Esen
authors.forename: Rolf
authors.initials: R
authors.lastname: Fendel
authors.forename: Pablo Martinez
authors.initials: PM
authors.lastname: de Salazar
authors.forename: Raymund E
authors.initials: RE
authors.lastname: Mürbeth
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Imbault
authors.forename: Egeruan Babatunde
authors.initials: EB
authors.lastname: Imoukhuede
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Ramadhani A
authors.initials: RA
authors.lastname: Noor
authors.forename: Brenda
authors.initials: B
authors.lastname: Okech
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
mesh_terms: D000349:Africa; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C089133:merozoite surface protein 3, Plasmodium; C072492:glutamate-rich protein, Plasmodium