Most Polymorphic Residue on Plasmodium falciparum Apical Membrane Antigen 1 Determines Binding of an Invasion-Inhibitory Antibody

Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by Plasmodium merozoites and prevent the multiplication of blood-stage parasites. Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) th...

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Bibliographic Details
Published in:Infection and Immunity 2006-05, Vol.74 (5), p.2628-2636
Main Authors: Coley, A. M, Parisi, K, Masciantonio, R, Hoeck, J, Casey, J. L, Murphy, V. J, Harris, K. S, Batchelor, A. H, Anders, R. F, Foley, M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies, Monoclonal - immunology
Antibodies, Protozoan - immunology
Antigens, Protozoan - chemistry
Antigens, Protozoan - immunology
Biological and medical sciences
Epitope Mapping
Erythrocytes - parasitology
Fundamental and applied biological sciences. Psychology
Fungal and Parasitic Infections
Humans
Membrane Proteins - chemistry
Membrane Proteins - immunology
Microbiology
Molecular Sequence Data
Plasmodium falciparum
Plasmodium falciparum - immunology
Protein Conformation
Protozoan Proteins - chemistry
Protozoan Proteins - immunology
Species Specificity
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Summary:Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by Plasmodium merozoites and prevent the multiplication of blood-stage parasites. Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) that inhibits the invasion of Plasmodium falciparum parasites in vitro. We show that both reactivity of MAb 1F9 with AMA1 and MAb 1F9-mediated invasion inhibition were strain specific. Site-directed mutagenesis of a fragment of AMA1 displayed on M13 bacteriophage identified a single polymorphic residue in domain I of AMA1 that is critical for MAb 1F9 binding. The identities of all other polymorphic residues investigated in this domain had little effect on the binding of the antibody. Examination of the P. falciparum AMA1 crystal structure localized this residue to a surface-exposed [alpha]-helix at the apex of the polypeptide. This description of a polymorphic inhibitory epitope on AMA1 adds supporting evidence to the hypothesis that immune pressure is responsible for the polymorphisms seen in this molecule.
ISSN:1098-5522
0019-9567
1098-5522
DOI:10.1128/IAI.74.5.2628-2636.2006