Antibodies against Plasmodium falciparum malaria at the molecular level

Abstract

Malaria is a vector-borne disease of global importance, with the vast majority of its life-threatening cases caused by infection with Plasmodium falciparum parasites. Repeated exposure to P. falciparum leads to naturally occurring immunity, but this is not sterilizing and is relatively short-lived. However, antibodies can protect from the disease, as has been shown by serum transfer studies in humans and in animal models. Recent advances in single-cell antibody cloning technologies have enabled the characterization of recombinant monoclonal antibodies against parasite antigens at the molecular level. This work has significantly advanced our understanding of how protective antibodies against P. falciparum are generated, what their molecular features are, their epitope specificity and binding modes, and the formation of memory B cell responses. Here we review these recent advances, with a particular emphasis on human antibody responses. We discuss how these discoveries have laid the foundation for the development of novel intervention strategies, as well as having conceptual implications beyond the malaria field.