The conserved, nonantigenic, nonimmunogenic malaria Merozoite Surface Protein-2 peptide 1, having high affinity for red blood cells, was rendered immunogenic and protective in Aotus monkeys by specifically changing some critical residues. The NMR structure revealed a switch from classical type III' into distorted III' and III β turns in the protective peptides. These changes may lead to a better fit into the Aotus MHC class II human HLA-DRβ1* 12 molecule equivalent, thus activating the immune system.