Antibodies to Malaria Peptide Mimics Inhibit Plasmodium falciparum Invasion of Erythrocytes

摘要

The leading malaria vaccine candidate, Apical membrane antigen 1 (AMA1) is expressed on the surface of merozoite and sporozoite stage parasites and is thought to play an important role in the invasion of erythrocytes by malaria parasites. 4G2 is an AMA1 antibody known to inhibit P. falciparum invasion of erythrocytes. We have selected peptides that mimic the 4G2 epitope from a phage display library. The most 4G2-reactive of which (J1, J3 & J7) elicited antibody responses in rabbits that were inhibited erythrocyte invasion. As such they may be useful as in vitro correlates of protective immunity in AMA1 vaccine trials. NMR studies suggest that the well defined structures of J1 and a cyclysed Jl analogue will provide a clearer understanding of the complex conformational nature of the inhibitory 4G2 epitope on AMA1.