Targeting Bottlenecks in Malaria Transmission: Antibody-Epitope Descriptions Guide the Design of Next-Generation...

Malaria continues to pose a significant burden to global health. Thus, a strong need exists for the development of a diverse panel of intervention strategies and modalities to combat malaria and achieve elimination and eradication goals. Deploying interventions that target bottlenecks in the transmission life cycle of the causative agent of malaria, Plasmodium parasites, is an attractive strategy. The development of highly potent antibody-based biologics, including vaccines, can be greatly facilitated by an in-depth molecular understanding of antibody-epitope interactions. Here, we provide an overview of structurally characterized antibodies targeting lead vaccine candidates expressed during the bottlenecks of the Plasmodium life cycle which include the pre-erythrocytic and sexual stages. The repeat region of the circumsporozoite protein (CSP), domain 1 of Pfs230 and domains 1 and 3 of Pfs48/45 are critical Plasmodium regions targeted by the most potent antibodies at the two bottlenecks of transmission, with other promising targets emerging and requiring further characterization.