Last Updated: 29/01/2025
Identifying naturally occurring antibodies in women resistant to placental malaria to guide future therapeutic development
Objectives
Aim: To isolate at least 30 human monoclonal antibodies (hu-mAbs) specific to the VAR2CSA ectodomain from women living in Plasmodium falciparum (Pf) high transmission areas and evaluate their functional potency in-vitro.
Objective: Characterise naturally occurring, functional antibodies to VAR2CSA to inform design of a vaccine or therapeutic agent to protect against placental malaria (PM).
PM is a serious complication of Pf infection with a severe impact on maternal and infant heath. Pathology results from placental sequestration of infected erythrocytes (IE) via binding of the antigen VAR2CSA, expressed on the surface of IE, with placental chondroitin sulfate A (CSA). Women develop naturally acquired immunity to PM with increasing parity, mediated by antibodies against VAR2CSA. To date, vaccine development has focused on generating antibody responses to single domains of VAR2CSA, however, recent work suggests CSA binding is reliant on formation of a single conformational pocket involving multiple domains. This proposal sets to generate hu-mAbs from memory B cells collected from multiparous women living in areas of high Pf endemicity. These different antibody clones are likely to recognise a range of multi-domain binding epitopes presented in natural infection. After screening these antibodies for functional efficacy using an in-vitro assay of antibody-mediated inhibition of binding of IE to CSA, Susanne Hodgson will characterize the most potent to understand association between domain binding sites, variable region sequences and biophysical measurements and potency. This work will inform rational design of next-generation VAR2CSA vaccines for PM and may lead to the development of a therapeutic mAb.
Jun 2021 — Dec 2022
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