The fungal pathogen Candida albicans is the most pathogenic of the Candida species and causes millions of superficial mucosal infections and approximately 200,000 deaths per annum due to invasive and disseminated disease in susceptible patient populations. Fungal infections in immunocompromised patients have an unacceptably high mortality rate of approximately 40%, and the yearly healthcare expenditure for the treatment of fungal diseases is estimated to be $15 billion. The clinical treatment of fungal diseases is hampered by poor and time-consuming diagnostics, a limited repertoire of anti-fungal drugs, and increasing levels of resistance to anti-fungal prophylaxis. Crucially, there are currently no licensed vaccines against fungal pathogen. Recent attempts to formulate vaccines have involved delivering simple mixtures of peptide/protein components of the target fungi with adjuvants (without controlled chemical conjugation), and without specific synthetic control have met with limited success. This project will develop new vaccine candidates to Candida albicans, the leading cause of fungal infection in humans worldwide. Unlike previous efforts, a multi-valent approach will be employed, chemically coupling three proteins expressed by Candida albicans. This synthetic approach will ensure the concurrent delivery of multiple protein antigens to overcome barriers faced by previous attempts at developing vaccines. Specifically, the project will focus on the synthesis of multi-valent systems by conjugating proteins to the surface of either: i) dendrimeric scaffolds (3D nanoscale covalent structures) or ii) liposomes (3D nanoscale self-assembled structures). This multidisciplinary proposal will use cutting-edge methodologies to address an unmet clinical need in fungal immunology that will deliver exceptional value through innovative vaccine research against fungal pathogens that are an escalating threat to global health.
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