Peptides from PfEMP1 interacting with cytoadherence receptor gC1qR may provide broader protection against severe malaria

Malaria is a major public health problem. Estimates suggestthat there were over 249 million cases of malaria in the year 2022. Most of the severe malaria cases and almost all the malaria-related deaths are caused by malaria parasite Plasmodium falciparum. The malaria parasite P. falciparum has unique cytoadherence properties through which it sequesters in the host's microvascular endothelial cells. The P. falciparum-infected erythrocytes can bind to the host's microvascular endothelial cells, platelets, uninfected erythrocytes and other immune cells, such as dendritic cells, and sequester in the host's blood vasculature. The cytoadherence of P. falciparum-infected erythrocytes in the brain and placenta has been associated with severe malaria disease. Cytoadherence to microvascular endothelial cells causes obstruction in blood flow, endothelial cell activation, and the release of proinflammatory cytokines. Studies have also shown that the gC1qR-mediated cytoadherence of P. falciparum-infected erythrocytes to dendritic cells can lead to the inhibition of the dendritic cells and therefore may contribute to the immune suppression of the innate immune system of the host. Cytoadherence is mediated by specific receptor–ligand interactions. Earlier, we identified a novel receptor gC1qR for cytoadherence to brain microvascular endothelial cells and platelets. The P. falciparum-infected erythrocytes can bind to dendritic cells, platelets and brain microvascular endothelial cells via gC1qR as a receptor. Cytoadherence to gC1qR has been implicated in the pathogenesis of severe malaria by several studies. We have also mapped the interacting domain of PfEMP1 interacting with gC1qR. Since gC1qR has an important role in severe malaria pathogenesis and the inhibition of dendritic cells have a role in innate and adaptive immunity, a vaccine targeting gC1qR and its PfEMP1 ligand interaction will likely have a broader protection, eliciting a longer-lasting immunity against P. falciparum infections.