The pathogenesis of P. falciparum malaria during pregnancy is relatively well-understood, and provides a path to vaccine development based on naturally acquired immunity.

Placental parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1–2 pregnancies as they acquire antibodies that block IE adhesion to CSA.

The parasite surface protein VAR2CSA is a variant antigen that mediates parasite adhesion to CSA, but its large size and sequence variation are obstacles to vaccine development.

Two products are expected to enter human clinical studies in the near future based on N-terminal VAR2CSA fragments that have high binding affinity for CSA.

Additional proteins preferentially expressed by placental parasites are also being examined for their potential contribution to a placental malaria vaccine.