Antibody features towards VAR2CSA and CSA binding infected erythrocytes in a cohort of pregnant women from PNG

<p><i>Plasmodium falciparum </i>causes placental malaria, which results in adverse outcomes for mother and child. <i>P. falciparum</i> infected erythrocytes that express the parasite protein VAR2CSA on their surface can bind to placental chondroitin sulfate-A.  It has been hypothesized that naturally acquired antibodies towards VAR2CSA protect against placental infection, but it has proven difficult to use measures of antibody to identify individuals protected from disease. We used a systems serology approach to identify naturally acquired antibody features mid pregnancy that were associated with protection from placental malaria at delivery.  Machine learning techniques selected six out of 169 measured antibody features towards VAR2CSA that could predict (with 86% accuracy) whether a woman would subsequently have active placental malaria infection at delivery. Selected features were associated with inhibition of placental binding and/or opsonic phagocytosis of infected erythrocytes, and network analysis indicated that there are not one but multiple pathways to protection from placental malaria.</p>