Plasmodium spp., intracellular parasites of the phylum Apicomplexa, cause malaria, a disease that tragically claimed ~608,000 lives in 2022. Plasmodium falciparum (Pf) leads to the highest mortality rates among human Plasmodium spp. To survive in the bloodstream, Pf invades and replicates within red blood cells (RBCs) before bursting out to release more parasites. While vaccines targeting the liver stage of Plasmodium spp. have been developed, they are not fully protective, underscoring the urgent need for novel vaccines that target additional lifecycle stages, including the bloodstream stage.
One promising novel vaccine candidate is the essential PfRH5 protein, which interacts with the RBC receptor basigin during invasion. Neutralising anti-PfRH5 monoclonal antibodies (mAbs) bind to the tip of the PfRH5 protein, sterically blocking its interaction with basigin and preventing RBC invasion. Additionally, these mAbs induce a structural change in extracellular parasites, transforming them into an amoeboid form that morphologically resembles parasites in the early stages of intra-erythrocytic development. These forms are referred to as "pseudo-rings." Little is known about pseudo-ring formation and how this process contributes to the invasion-inhibitory effect of PfRH5 mAbs. Therefore, this formed the basis of my project.
My study aimed to resolve how efficiently different PfRH5 mAbs induce pseudo-ring formation and the speed with which mAb-treated parasites convert into pseudo-rings. Through live-cell microscopy, I have demonstrated that neutralising anti-PfRH5 mAbs significantly increase pseudo-ring formation, with approximately five times more parasites converting into pseudo-rings compared to a negative antibody control. Moreover, the conversion to pseudo-rings occurred more rapidly in the presence of neutralising mAbs.
These novel findings, building on previous research in the field, provide valuable insights into how neutralising mAbs against vaccine candidate PfRH5 disrupt the parasite's invasion of RBC. This research has the potential to inform the development of more effective blood-stage malaria vaccines.