Optimising inhibition of binding of fresh Plasmodium falciparum isolates from pregnant women to chondroitin sulphate A using DBL4-VAR2CSA antibodies

Pregnancy associated malaria (PAM) has serious consequences for mother and child. VAR2CSA has been identified as the main protein involved in the pathogenesis of PAM. The PI's earlier Gates Malaria Partnership funded projects have shown that the VAR2CSA protein is expressed on the surface of laboratory isolates as well as parasites isolated directly from the placenta. Research currently focuses on what part of this very large molecule should be used in a recombinant vaccine. Recent data show that we can induce antibodies against the DBL4-VAR2CSA domain that inhibit parasite binding. As part of on-going studies, DBL4-VAR2CSA antibodies are being produced at the Centre for Medical Parasitology, University of Copenhagen, Denmark, and parasites are being collected from pregnant women in Korogwe, Tanzania, where inhibition of binding assays (IBA) will be performed. The IBA is currently sub-optimal and low throughput, in this study proposal we aim to develop an optimal high throughput IBA applicable to a field setting, in order to demonstrate that DBL4-VAR2CSA antibodies inhibit binding of parasites directly isolated from pregnant women with PAM.