Identifying vaccine targets for Plasmodium falciparum and Schistosoma mansoni through systematic functional studies of large libraries of recombinant extracellular parasite proteins
Malaria and schistosomiasis are two of the most prevalent parasitic diseases in the world, causing an estimated combined toll of 700,000 deaths per year. Despite their high morbidity and huge social and economic impact in developing countries, no effective vaccine is available. Because they are directly exposed to host antibodies, cell surface and secreted parasite proteins constitute excellent vaccine targets and are the main protagonists of host-parasite interactions. Their correct folding is mostly dictated by the presence of disulphide bonds in their extracellular domain that are essential for their tertiary structure and function. Yet, producing functional extracellular proteins recombinantly can be challenging and is often a limitation in functional and vaccine studies. Taking advantage of recent advances in genomic, proteomic and transcriptomic studies, we have compiled and produced in mammalian cells large libraries of cell-surface and secreted proteins from two major parasites: Plasmodium falciparum, the aetiological agent for the most severe form of malaria, and Schistosoma mansoni, which is responsible for intestinal schistosomiasis. The generation of these large collections of biochemically active recombinant proteins has allowed us to investigate the biology of these two deadly parasites through systematic serological analyses, host-parasite protein-protein interaction studies, and vaccine target identification.
In this talk, I will present how these systematic screening strategies have identified the interaction between the P. falciparum Rh5 and the human receptor Basigin, which has proved to be essential and universally required by all P. falciparum strains tested to date for human erythrocyte invasion. I will also discuss our most recent use of recombinant S. mansoni proteins in the context of vaccine studies and the identification of early serological markers of infection.
The seminar will be hosted using Zoom. A Google calendar invite featuring the Zoom link will be sent to Biology staff and students before the seminar date. For all enquiries please contact Biology DMT Hub.