Publications & Reports

Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria.

Aitken EH, Damelang T, Ortega-Pajares A, Alemu A, Hasang W, Dini S, Unger HW, Ome-Kaius M, Nielsen MA, Salanti A, Smith J, Kent S, Hogarth PM, Wines BD, Simpson JA, Chung A, Rogerson SJ
Medicine (RMH), The University of Melbourne, Melbourne, Australia.


Background: Plasmodium falciparum causes placental malaria, which results in adverse outcomes for mother and child. P. falciparum 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 identify robust antibody correlates of protection from disease. The objective of this study was to develop a prediction model using antibody features which could identify women protected from placental malaria. Methods: We used a systems serology approach with elastic net-regularized logistic regression, Partial Least Squares Discriminant Analysis and a case control study design to identify naturally acquired antibody features mid pregnancy that were associated with protection from placental malaria at delivery in a cohort of 77 pregnant women from Madang, Papua New Guinea. Results: The 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 included previously described associations 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. Conclusions: We have identified candidate antibody features which could accurately identify malaria-infected women as protected from placental infection. It is likely that there are multiple pathways to protection against placental malaria. Funding: This study was supported by the National Health and Medical Research Council (No. APP1143946, GNT1145303, APP1092789, APP1140509 and APP1104975)

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  • Journal: eLife
  • Published: 29/06/2021
  • Volume: 10
  • Pagination: e65776