Identification of regions of apical membrane antigen 1 of apicomplexan parasites suitable for targeting by vaccines and drugs by derivation and analysis of the three-dimensional structure

摘要

The present invention relates to a crystal of the ectoplasmic domain of Apical Membrane Protein 1 (AMA1) from Plasmodium and a method of crystallisation of such a protein. The invention is also directed to the crystal structure of this AMA1 domain and to the three-dimensional structure of the domain itself, particularly of AMA1 ectodomain from Plasmodium vivax and Plasmodium falciparum . The present invention also provides methods for identifying ligands of this AMA1 ectodomain using the said crystal structure, and to design pharmaceutical compounds capable of interacting or binding to that domain, particularly to certain amino-acid residues of domain I and II identified as contributing to a relevant epitope of that domain, or for identifying vaccine or drug candidates that could be used to inhibit erythocytes invasion by, and/or growth inhibition of, Plasmodial parasites and that can used in pharmaceutical compositions for the prevention or treatment of malaria. The present invention also concerns peptidic fragments on that AMA1 ectodomain, their coding nucleic acid and their uses for the preparation of immunogens or vaccines for the treatment or the prevention of Plasmodial infection.