Plasmodium falciparum infection during pregnancy is a major cause of morbidity and mortality for both mother and child. Despite high levels of immunity acquired over years of malaria exposure, adult women become susceptible to malaria again during their first pregnancy, when parasites sequester in the placenta. Infected erythrocytes (IE) causing placental malaria (PM) bind to the receptor chondroitin sulfate A (CSA), and women develop specific immunity to CSA-binding IE over successive pregnancies, suggesting that a vaccine is feasible. Microarray studies recently revealed that several conserved genes are upregulated in PM parasites, in addition to the variant var2CSA gene. In this study we hypothesized that conserved genes upregulated in PM parasites contribute to the CSA-binding phenotype during pregnancy malaria. Here we demonstrate that the conserved protein PfCSA-L is exported to the surface of maternal iRBC to bind CSA. Recombinant PfCSA-L and antisera against this protein inhibit binding of maternal iRBC to CSA and to placental cryosections. Plasma from immune African multigravidae blocks PfCSA-L adhesion to CSA. PfCSA-L localizes with VAR2CSA on the surface "knobs" of CSA-binding maternal iRBC but not VAR2CSA-disrupted parasites, and therefore these proteins might act cooperatively to mediate placental parasites adhesion. PfCSA-L is expressed by all parasite isolates, but only translocates to the surface of maternal iRBC; antibodies to PfCSA-L are common in children and adult males, but only multigravidae acquire functional antibodies. PfCSA-L is the first conserved iRBC surface protein to be identified, and a novel target for a pregnancy malaria vaccine.
|School:||University of Washington|
|School Location:||United States -- Washington|
|Source:||DAI-B 72/11, Dissertation Abstracts International|
|Subjects:||Molecular biology, Parasitology|
|Keywords:||Malaria, Plasmodium falciparum, Pregnancy|
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