Authors

T A Rawlinson¹; S elias¹; D analine¹; R payne¹; S silk¹; D llewellyn¹; S Draper¹; J jin¹;  ¹ The Jenner Institute, University of Oxford

Discussion

It has been known for over a century that most people of West African descent are naturally protected from Plasmodium vivax (Pv) malaria. In the 1970s this was determined to be due to these populations lacking the Duffy Antigen Receptor for Chemokines (DARC) on their erythrocytes. It has since been shown that the Pv merozoite binds to DARC via a micronemal protein called ‘Duffy-binding protein’ (PvDBP). This crucial host-parasite interaction has long been considered an Achilles’ heel in the parasite’s life-cycle and a potential intervention point for vaccine-induced antibodies.

 

Despite DARC’s essential role being known about for 40 years and decades of pre-clinical work on the parasite ligand, it was not until last year that PvDBP was finally put to the test in a human vaccine trial. This trial took place at The Jenner Institute, Oxford and was the first clinical trial of a vaccine against blood-stage Pv malaria. We have shown that the PvDBP vaccine-induced sera inhibit binding between recombinant PvDBP and DARC in vitro, across a range of PvDBP allelic variants. We have also succeeded in isolating, cloning and expressing the first panel of fully human monoclonal antibodies (hmAbs) against PvDBP from the B cells of vaccinated volunteers. Binding kinetics and epitope mapping by competition-based ELISA assays have been undertake