Allelic polymorphisms in apical membrane antigen‐1 are responsible for evasion of antibody‐mediated inhibition in Plasmodium falciparum

• DOI: 10.1111/j.1365-2958.2003.03974.x
• Publication Date: 2004-12-27T23:00:22Z
• Authors: Julie Healer; Vince Murphy; Anthony N. Hodder; Rosella Masciantonio; Alan W. Gemmill; Robin F. Anders; Alan F. Cowman; Adrian Batchelor
• Keywords: Heterologous; Apical membrane

Summary Apical membrane antigen‐1 (AMA‐1) is a target of antibodies that inhibit invasion Plasmodium falciparum into human erythrocytes and candidate for inclusion in malaria vaccine. We have identified line P. (W2mef) less susceptible to anti‐AMA1 raised the protein from heterologous parasite (3D7). constructed transgenic expressing AMA‐1 alleles. In vitro assays show these parasites differ parental lines susceptibility inhibitory antibodies, providing direct evidence sequence polymorphisms within are responsible evasion immune responses invasion. also generated would express chimeric protein, which highly polymorphic residues domain 1 were exchanged. Inhibition suggest not sufficient inhibition by invasion‐blocking antibodies. This study first use allelic exchange examine relationship between genetic diversity protective The findings important implications development an AMA‐1‐based