Pre-erythrocytic malaria vaccines: identifying the targets

Abstract

Pre-erythrocytic malaria vaccines target Plasmodium during its sporozoite and liver stages, and can prevent progression to blood-stage disease, which causes a million deaths each year. Whole organism sporozoite vaccines induce sterile immunity in animals and humans and guide subunit vaccine development. A recombinant protein-in-adjuvant pre-erythrocytic vaccine called RTS,S reduces clinical malaria without preventing infection in field studies and additional antigens may be required to achieve sterile immunity. Although few vaccine antigens have progressed to human testing, new insights into parasite biology, expression profiles and immunobiology have offered new targets for intervention. Future advances require human trials of additional antigens, as well as platforms to induce the durable antibody and cellular responses including CD8(+) T cells that contribute to sterile protection.

Figure 1. The pre-erythrocytic journey of the Plasmodium parasite in the mammalian host

After injection into the skin by an infected female Anopheles mosquito, some sporozoites may develop in the skin, some migrate to the draining lymph node where they can be processed and presented to T cells, and some enter the bloodstream and reach the liver for complete development. After reaching the liver, sporozoites pass through the layer of Kupffer and endothelial cells to access liver parenchymal cells. A sporozoite may pass through multiple cells before forming a parasitophorous vacuole within a final hepatocyte, within which it undergoes liver stage development and gives rise to tens of thousands of merozoites. These merozoites are then released into the bloodstream as merozoite-filled packets called merosomes. DC: Dendritic cell; LS: Liver stage.