title: Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1.
abstract: BACKGROUND
  Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).
  
  
  METHODS
  Using recombinant proteins corresponding to five domains of the expressed A4 var gene, A4 PfEMP1, the naturally occurring antibody response was assessed, by ELISA, to each domain in serum samples obtained from individuals resident in two communities of differing malaria transmission intensity on the Kenyan coast. Using flow cytometry, the correlation in individual responses to each domain with responses to intact A4-infected erythrocytes expressing A4 PfEMP1 on their surface as well as responses to two alternative parasite clones and one clinical isolate was assessed.
  
  
  RESULTS
  Marked variability in the prevalence of responses between each domain and between each transmission area was observed, as wasa strong correlation between age and reactivity with some but not all domains. Individual responses to each domain varied strikingly, with some individuals showing reactivity to all domains and others with no reactivity to any, this was apparent at all age groups. Evidence for possible cross-reactivity in responses to the domain DBL4gamma was found.
  
  
  CONCLUSIONS
  Individuals acquire antibodies to surface expressed domains of a highly variant protein. The finding of potential cross-reactivity in responses to one of these domains is an important initial finding in the consideration of potential vaccine targets.
authors.affiliation: Kenya Medical Research Institute Centre for Geographic Medicine Research Coast, Kilifi District Hospital, Kilifi, Kenya. c.mackintosh@talk21.com
authors.forename: Claire L
authors.initials: CL
authors.lastname: Mackintosh
authors.forename: Zoe
authors.initials: Z
authors.lastname: Christodoulou
authors.forename: Tabitha W
authors.initials: TW
authors.lastname: Mwangi
authors.forename: Moses
authors.initials: M
authors.lastname: Kortok
authors.forename: Robert
authors.initials: R
authors.lastname: Pinches
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Newbold
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005434:Flow Cytometry; D005843:Geography; D006801:Humans; D007223:Infant; D007630:Kenya; D016778:Malaria, Falciparum / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum