Distorting malaria peptide backbone structure to enable fitting into MHC class II molecules renders modified peptides immunogenic and protective.

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 beta turns in the protective peptides. These changes may lead to a better fit into the Aotus MHC class II human HLA-DRbeta1 12 molecule equivalent, thus activating the immune system.