Project: Identifying globally conserved malaria virulence determinants as vaccine candidates
P. falciparum employs a diverse armoury of variant surface proteins to hide from immunity, but only some of these proteins cause severe disease and possibly they could be used in a life-saving vaccine. The malaria parasite Plasmodium falciparum caused the deaths of approximately 435,000 people in 2017, most of whom were children. P. falciparum multiplies inside our red blood cells and bursts out every 48 hours causing periodic fever. How P. falciparum causes severe malaria is complex but involves loss of red blood cells, obstruction of blood vessels in critical organs and development of an inappropriate immune response.
P. falciparum encodes a diverse armoury of PfEMP1 variant proteins that are exported to the surface of the infected erythrocyte. It switches between the PfEMP1s expressed on the surface of the infected erythrocyte enabling it to escape from immunity. The PfEMP1s bind to endothelial receptors in the microvasculature sequestering the infected cells from the circulation and preventing their destruction in the spleen. We and others recently showed that only a subset of virulent PfEMP1s are associated with severe disease, if sufficiently conserved these virulent PfEMP1s could possibly be used in a life-saving vaccine. This project would identify which of these virulent PfEMP1s are globally conserved and how widely they are recognised by antibodies from patients recovering, or protected from, severe malaria.