Conserved Epitopes in Rosetting PfEMP1 Variants: Prevalence will Inform Potential as a Therapeutic Target in Severe Malaria (360G-Wellcome-204052_Z_16_A)

Rosetting, where parasitised red blood cells bind to non-parasitised red blood cells, has consistently been associated with severe forms of Plasmodium falciparum malaria. There is therefore interest in the development of anti-rosetting therapies which aim to alleviate the microvascular obstruction caused by rosettes. However, the highly polymorphic nature of the parasite-derived antigen family, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), responsible for rosetting has made this challenging. A recent report showed that polyclonal sera from rabbits immunised with the N-terminal domain of two rosette mediating PfEMP1 variants showed extensive recognition of heterologous rosetting parasite lines. These cross-reactive antibodies suggest that conserved epitopes exist on some rosette mediating PfEMP1 molecules. Here, we propose to develop a monoclonal antibody targeting one of these cross-reactive epitopes. This will allow us to characterise the epitope, and to estimate the percentage of severe malaria clinical isolates displaying this target. Fundamentally, the work proposed here aims to determine whether one of the cross-reactive epitopes recognised by the rabbit cross-reactive polyclonal sera has therapeutic potential, either as a target for a molecular therapy, or as the basis for a vaccine against rosette mediated disease.