title: Different Regions of Plasmodium falciparum Erythrocyte-Binding Antigen 175 Induce Antibody Responses to Infection of Varied Efficacy.
abstract: Increasing evidence suggests that antibodies against merozoite proteins involved in Plasmodium falciparum invasion into the red blood cell play an important role in clinical immunity to malaria. Erythrocyte-binding antigen 175 (EBA-175) is the best-characterized P. falciparum invasion ligand, reported to recognize glycophorin A on the surface of erythrocytes. Its protein structure comprises 6 extracellular regions. Whereas region II contains Duffy binding-like domains involved in the binding to glycophorin A, the functional role of regions III-V is less clear.
  
  
  
  We developed a novel cytometric bead array for assessment of antigen-specific antibody concentration in plasma to evaluate the efficacy of immune responses to different regions of EBA-175 and associations between antibody levels with protection from symptomatic malaria in a treatment-reinfection cohort study.
  
  
  
  We found that while antibodies to region II are highly abundant, circulating levels as low as 5-10 µg/mL of antibodies specific for region III or the highly conserved regions IV-V predict strong protection from clinical malaria.
  
  
  
  These results lend support for the development of conserved regions of EBA-175 as components in a combination of a malaria vaccine.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Chris Y
authors.initials: CY
authors.lastname: Chiu
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: White
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Healer
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Thompson
authors.affiliation: Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hansen
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D052940:Merozoites / Q000276:immunology*; D008962:Models, Theoretical; D010219:Papua New Guinea; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding
chemical_list: D000953:Antigens, Protozoan
keywords: Plasmodium falciparum; antibodies; erythrocyte-binding antigen 175; immunity; malaria