Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

Abstract

More than 50 years ago the owl monkey (genusAotus) was found to be highly susceptible to developinghuman malaria, making it an excellent experimental model for this disease. Microbes and parasites'(especially malaria) tremendous genetic variability became resolved during our malaria vaccine devel-opment, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPsare immunologically silent and must be specially modified (mHABPs) to induce a perfectfit into majorhistocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainlyantibody-mediated and controlled by the HLA-DRB genetic region, ~1000Aotushave been molecularlycharacterised for MHC-DRB, revealing striking similarity between human andAotusMHC-DRB reper-tories. Such convergence suggested that a large group of immune protection-inducing protein structures(IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge inAotus,could easily be used in humans for inducing full protection against malaria. We highlight the value of alogical and rational methodology for developing a vaccine in an appropriate animal model:Aotusmonkeys