title: Antibodies to Plasmodium falciparum merozoite surface protein-1p19 malaria vaccine candidate induce antibody-dependent respiratory burst in human neutrophils.
abstract: BACKGROUND
  Identification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development. Among functional assays, the neutrophil antibody-dependent respiratory burst (ADRB) induced by opsonized Plasmodium falciparum merozoites has been correlated with acquired immunity to clinical malaria in endemic areas, but the target merozoite antigens are unknown. Here, the contribution of antibodies to the conserved C-terminal domain of the P. falciparum merozoite surface protein-1 (PfMSP1p19) in mediating ADRB was investigated in sera from individuals living in two Senegalese villages with differing malaria endemicity.
  
  
  METHODS
  Anti-PfMSP1p19 antibody levels in sera from 233 villagers were investigated and the involvement of anti-PfMSP1p19 antibodies in ADRB was explored in a subset of samples using (1) isogenic P. falciparum parasite clones expressing P. falciparum or Plasmodium chabaudi MSP1p19; (2) PfMSP1p19-coated plaque ADRB; and, (3) ADRB triggering using sera depleted from PfMSP1p19 antibodies by absorption onto the baculovirus recombinant antigen.
  
  
  RESULTS
  ADRB activity correlated with anti-PfMSP1p19 IgG levels (P < 10(-3)). A substantial contribution of PfMSP1p19 antibody responses to ADRB was confirmed (P < 10(-4)) in an age-adjusted linear regression model. PfMSP1p19 antibodies accounted for 33.1 % (range 7-54 %) and 33.2 % (range 0-70 %) of ADRB activity evaluated using isogenic merozoites (P < 10(-3)) and depleted sera (P = 0.0017), respectively. Coating of PfMSP1p19 on plates induced strong ADRB in anti-PfMSP1p19-positive sera.
  
  
  CONCLUSIONS
  These data show that naturally acquired P. falciparum MSP1p19 antibodies are potent inducers of neutrophil ADRB and support the development of PfMSP1p19-based malaria vaccine using ADRB assay as a functional surrogate for protection.
authors.affiliation: Unité d'Immunologie, Institut Pasteur de Dakar, Dakar, Senegal. charlottejoos@yahoo.fr.|Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, Paris, France. charlottejoos@yahoo.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Joos
authors.affiliation: Unité d'Immunologie, Institut Pasteur de Dakar, Dakar, Senegal. lvarela@pasteur.sn.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Varela
authors.affiliation: Unité d'Immunogénétique/UCAD, Institut Pasteur de Dakar, Dakar, Senegal. bmbengue@pasteur.sn.
authors.forename: Babacar
authors.initials: B
authors.lastname: Mbengue
authors.affiliation: Unité d'Immunologie, Institut Pasteur de Dakar, Dakar, Senegal. mansourouannick@yahoo.fr.
authors.forename: Annick
authors.initials: A
authors.lastname: Mansourou
authors.affiliation: Unité d'Epidémiologie, Institut Pasteur de Dakar, Dakar, Senegal. Laurence.Marrama@ecdc.europa.eu.
authors.forename: Laurence
authors.initials: L
authors.lastname: Marrama
authors.affiliation: Institut de Recherche pour le Développement (IRD), URMITE, Dakar, Senegal. cheikh.sokna@ird.fr.
authors.forename: Cheikh
authors.initials: C
authors.lastname: Sokhna
authors.affiliation: Unité d'Epidémiologie, Institut Pasteur de Dakar, Dakar, Senegal. tall@pasteur.sn.
authors.forename: Adama
authors.initials: A
authors.lastname: Tall
authors.affiliation: Institut de Recherche pour le Développement (IRD), URMITE, Dakar, Senegal. jean-francois.trape@ird.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Trape
authors.affiliation: Unité d'Immunologie, Institut Pasteur de Dakar, Dakar, Senegal. atoure@pasteur.sn.
authors.forename: Aissatou
authors.initials: A
authors.lastname: Touré
authors.affiliation: Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur, Paris, France. odile.puijalon@pasteur.fr.
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.affiliation: Unité d'Immunologie, Institut Pasteur de Dakar, Dakar, Senegal. perraut@pasteur.sn.
authors.forename: Ronald
authors.initials: R
authors.lastname: Perraut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology*; D016788:Plasmodium chabaudi / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D016897:Respiratory Burst; D012675:Senegal; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1