title: Human antibodies to recombinant protein constructs of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) and their associations with protection from malaria.
abstract: Serum antibodies from 1071 people in two Kenyan villages were assayed using eight different recombinant Apical Membrane Antigen 1 (AMA1) protein constructs to investigate their role in naturally acquired immunity. In both communities, antibodies against the full-length ectodomain (both FVO and 3D7 allele constructs) prior to a malaria transmission season were significantly associated with protection from malaria in the following 6 months, even after adjusting for age and antibody reactivity to whole parasite (schizont) extract. However, these protective associations of antibodies were only seen among subjects that were parasite slide positive at the time of pre-season serum sampling. Competition ELISAs with the FVO and 3D7 allele constructs showed that antibodies can recognise either conserved or allele-specific epitopes in AMA1. Results encourage the development of an AMA1 vaccine based on the full-length ectodomain, and indicate that the function of human antibodies to allele-specific and conserved epitopes in AMA1 should be studied further.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. spencer.polley@lshtm.ac.uk
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Polley
authors.forename: Tabitha
authors.initials: T
authors.lastname: Mwangi
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Ed
authors.initials: E
authors.lastname: Remarque
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Mwambingu
authors.forename: Brett
authors.initials: B
authors.lastname: Lowe
authors.forename: David J
authors.initials: DJ
authors.lastname: Conway
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016036:Seroepidemiologic Studies
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium