Protection against experimental P falciparum malaria is associated with short AMA-1 peptide analogue alpha-helical...

Apical membrane antigen-1 (AMA-1) is an integral Plasmodium falciparum malaria parasite membrane protein. Peptides having high activity binding to human red blood cells have been identified in this protein. One of them, peptide 4325, with the amino acid sequence MIKSAFLPTGAFKADRYKSH, for which critical binding residues have already been defined (underlined), is conserved and non-immunogenic. Its critical binding residues were changed for amino acids having similar mass but different charge to change such immunological properties. These changes rendered some peptides immunogenic and protective against experimental challenge in Aotus monkeys. Three-dimensional models of peptide 4325 and its analogues, 20032 and 20034, were calculated from NMR experiments with distance geometry and restrained molecular dynamic methods. Non-immunogenic, non-protective peptide 4325 showed differences in its secondary structure with respect to protective, immunogenic peptides 20032 and 20034. Such data suggest that these modifications could have converted non-immunogenic peptides into immunogenic, protective ones, making them excellent candidates for a multi-component subunit synthetic malaria vaccine.