title: Apical membrane antigen 1, a major malaria vaccine candidate, mediates the close attachment of invasive merozoites to host red blood cells.
abstract: Apical membrane antigen 1 (AMA-1) of Plasmodium merozoites is established as a candidate molecule for inclusion in a human malaria vaccine and is strongly conserved in the genus. We have investigated its function in merozoite invasion by incubating Plasmodium knowlesi merozoites with red cells in the presence of a previously described rat monoclonal antibody (MAb R31C2) raised against an invasion-inhibitory epitope of P. knowlesi AMA-1 and then fixing the material for ultrastructural analysis. We have found that the random, initial, long-range (12 nm) contact between merozoites and red cells occurs normally in the presence of the antibody, showing that AMA-1 plays no part in this stage of attachment. Instead, inhibited merozoites fail to reorientate, so they do not bring their apices to bear on the red cell surface and do not make close junctional apical contact. We conclude that AMA-1 may be directly responsible for reorientation or that the molecule may initiate the junctional contact, which is then presumably dependent on Duffy binding proteins for its completion.
authors.affiliation: Department of Immunobiology, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, London SE1 9RT, United Kingdom. g.h.mitchell@kcl.ac.uk
authors.forename: G H
authors.initials: GH
authors.lastname: Mitchell
authors.forename: A W
authors.initials: AW
authors.lastname: Thomas
authors.forename: G
authors.initials: G
authors.lastname: Margos
authors.forename: A R
authors.initials: AR
authors.lastname: Dluzewski
authors.forename: L H
authors.initials: LH
authors.lastname: Bannister
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D008253:Macaca mulatta; D008288:Malaria / Q000517:prevention & control; D017780:Malaria Vaccines; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D016790:Plasmodium knowlesi / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium