Antibody-based Therapies and Diagnostics for Fungal Infections

Opportunistic invasive fungal pathogens cause over two million life-threatening infections per year worldwide with mortality ranging from 20–95%. At least as many, if not more people die from invasive fungal diseases every year than from malaria or tuberculosis. There is therefore an urgent clinical need for the development of diagnostics and new therapeutics for fungal diseases which research in my group aims to address in innovative ways.

Research in my group is focused on Candida albicans which is the most common serious fungal pathogen of humans. C. albicans colonises the gut of most healthy individuals but does not usually cause serious disease because the physical barriers between our gut and the bloodstream, combined with our immune defences and the suppressive powers of the indigenous gut microbiota, prevent these infections. However, this opportunistic fungal pathogen can cause serious, life-threatening disseminated disease when these barriers and defences are compromised (e.g. seriously ill patients in the ICU, during cancer chemotherapy, organ/stem cell transplantation, or when the gut microbiota is disturbed), which renders them vulnerable to infections from the C. albicans that colonises their gut. Despite the availability of antifungal drugs, over 40% of these systemic infections are fatal in certain patient groups.

The cell wall of C. albicans is made up of sugars and proteins, many of which are not found in humans. Therefore, antibodies that recognise components of the fungal cell surface may provide bio-tools for the development of diagnostic and therapeutic agents with utility against fungal infections. They will also provide a much-needed alternative to the current inadequate range of chemical-based antifungal drugs. Using phage-display technology, antibody fragments which recognise specific cell surface components of C. albicans have been isolated.

The aim of this project is to demonstrate the therapeutic and diagnostic utility of these antibodies.

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