Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1 (AMA-1), comparison with P-falciparum AMA-1, and antibody-mediated inhibition of red cell invasion

Apical membrane antigen 1 is a candidate vaccine component for malaria. It is encoded by a single copy gene and has been characterised in a number of malaria species as either an 83-kDa de novo product (Plasmodium falciparum: Pf AMA-1) or a 66-kDa product (all other species). All members of the AMA- 1 family are expressed during merozoite formation in maturing schizonts and are initially routed to the rhoptries. Processed forms may subsequently be associated with the merozoite surface. Because of the unique occurrence of the 83-kDa form in P. falciparum we were interested to determine whether t he phylogenetically closely related chimpanzee malaria plasmodium reichenow i shared characteristics with Pf AMA-1. Here we show that the molecular str ucture, the localisation and processing are similar to that of Pf AMA-1 and that in vitro growth inhibitory mAbs reactive with Pf AMA-1 also inhibit P . reichenowi growth in an in vitro assay. Polymorphism in the 83-kDa AMA-1 family was analysed through comparison of Pr ama-1 with Pf ama-1 alleles, w hich showed the most significant evidence for selection maintaining polymor phism in Domains I-III of AMA-1 in P. falciparum. The most substantial dive rgence between Pr AMA-1 and Pf AMA-1 sequences was in the N-terminal region unique to the 83-kDa form of AMA-1. It was confirmed that the specific Pr ama-1-type allele was not present among P. falciparum parasites in an Afric an population, and an allele coding for lysine at amino acid 187 was unique ly associated with field isolates in this population. (C) 2000 Elsevier Sci ence B.V. All rights reserved.