To date, efforts to develop a truly prophylactic pregnancy associated malaria vaccine have been hindered by the difficulty in identifying immunogens that elicit broadly neutralizing and adhesion-blocking antibodies. Therefore, it is of the highest priority that a focused effort is undertaken to decipher the molecular basis for the CSA binding to the parasite ligands in order to define the common features within the different CSA binding domains and the cross-reactive epitopes that are likely to be the targets of natural protective antibodies. This knowledge will not only be very helpful in the design of novel CSA-binding PfEMP1 antigens capable of inducing broad and potent neutralising antibodies to a wide variety of strains, but also to identify molecules with inhibitory capacity that could be considered for therapeutic strategies as anti-adhesive drugs.

Consistently, this consortium is aiming to:

• Solve the three-dimensional structure of different CSA-binding DBL domains within var1 and var2CSA

• Define the stoichiometric and spatial requirements for a productive CSA/PfEMP1 interaction under both static and flow conditions.

• Create an in vivo model that would permit small animal validations of vaccination and small molecule inhibitors strategies.

PreMalStruct targets key knowledge gaps in understanding the molecular basis for PE binding to CSA during pregnancy-associated malaria and will definitively be a crucial step towards the design of novel vaccine and therapeutic strategies to provide protection against pregnancy associated malaria.