title: The malaria vaccine candidate GMZ2 elicits functional antibodies in individuals from malaria endemic and non-endemic areas.
abstract: BACKGROUND
  GMZ2 is a hybrid protein consisting of the N-terminal region of the glutamate-rich protein fused in frame to the C-terminal region of merozoite surface protein 3 (MSP3). GMZ2 formulated in Al(OH)3 has been tested in 3 published phase 1 clinical trials. The GMZ2/alum formulation showed good safety, tolerability, and immunogenicity, but whether antibodies elicited by vaccination are functional is not known.
  
  
  METHODS
  Serum samples prior to vaccination and 4 weeks after the last vaccination from the 3 clinical trials were used to perform a comparative assessment of biological activity against Plasmodium falciparum.
  
  
  RESULTS
  We showed that the maximum level of immunoglobulin G (IgG) antibodies obtained by GMZ2 vaccination is independent of ethnicity, time under malaria-exposure, and vaccine dose and that GMZ2 elicits high levels of functionally active IgG antibodies. Both, malaria-naive adults and malaria-exposed preschool children elicit vaccine-specific antibodies with broad inhibitory activity against geographically diverse P. falciparum isolates. Peptide-mapping studies of IgG subclass responses identified IgG3 against a peptide derived from MSP3 as the strongest predictor of antibody-dependent cellular inhibition.
  
  
  CONCLUSIONS
  These findings suggest that GMZ2 adjuvanted in Al(OH)3 elicits high levels of specific and functional antibodies with the capacity to control parasite multiplication.
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Denmark.
authors.forename: Micha Phill Grønholm
authors.initials: MP
authors.lastname: Jepsen
authors.forename: Prajakta S
authors.initials: PS
authors.lastname: Jogdand
authors.forename: Susheel K
authors.initials: SK
authors.lastname: Singh
authors.forename: Meral
authors.initials: M
authors.lastname: Esen
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Saadou
authors.initials: S
authors.lastname: Issifou
authors.forename: Aurore B
authors.initials: AB
authors.lastname: Hounkpatin
authors.forename: Ulysse
authors.initials: U
authors.lastname: Ateba-Ngoa
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Morten H
authors.initials: MH
authors.lastname: Dziegiel
authors.forename: Severin
authors.initials: S
authors.lastname: Olesen-Larsen
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000913:Antibodies, Protozoan / Q000097:blood*; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide
keywords: ADCI; GLURP; GMZ2; MSP3; Plasmodium falciparum; antibody; avidity; clinical trial; immunity; vaccine