Potential Protein Target for Placental Malaria Identified and Characterized

NIAID Now | October 29, 2021

Plasmodium falciparum, the parasite that causes malaria, creates a significant burden of morbidity and mortality around the world. In pregnant women, P falciparum- infected red blood cells (iRBCs) collect in vascular spaces of the placenta by binding to chondroitin sulfate A (CSA). This sequestration of iRBCs can result in inflammatory responses, which can lead to many adverse pregnancy outcomes such as severe maternal anemia, fetal growth retardation, premature delivery, maternal and/or perinatal mortality.

In pregnant women, VAR2CSA, a parasite protein, binds to CSA and has been shown to facilitate placental sequestration of iRBCs.  In addition, several other genes are upregulated in maternal parasites, including Plasmodium falciparum chondroitin sulfate A ligand (PfCSA-L).  These proteins serve as promising targets for the development of placental malaria interventions.

This study showed that PfCSA-L binds both placental CSA and VAR2CSA and is co-expressed on the iRBC surface. Examination of plasma from East African children, men, and women revealed significant differences in antibody levels to PfCSA-L between the groups.  Additionally, plasma from women who had multiple pregnancies potently blocked binding of PfCSA-L to CSA while plasma from men and women with their first pregnancy did not.  Taken together with data from previous studies, this data suggests PfCSA-L could be a promising target for the development of malaria vaccines.

Keitany et al. An Invariant Protein That Colocalizes With VAR2CSA on Plasmodium falciparum-Infected Red Cells Binds to Chondroitin Sulfate A. The Journal of Infectious Diseases, 2021, jiab550.

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