In vivo efficacy of an innovative vaccine approach targeting debilitating and life-threatening mucorales infections – KU Leuven

Lead applicant

Dr Greetje Vande Velde – KU Leuven

Co-applicants

Ulrike Binder – Medical University Innsbruck, Austria

Kai Dallmeier – KU Leuven

Katrien Lagrou – UZ Leuven

Victoriano Garre Mula – University of Murcia

Agustin Resendiz Sharpe – KU Leuven

Geographical focus – LMICs

Research Theme – Microbial Pathogenesis

Lay summary

Fungal infections, particularly mucormycosis, caused by representatives of Mucorales, present a significant global health risk with high mortality rates (50-80%) and life-altering morbidities like facial deformities in survivors. Cases are rising globally, especially in low- and middle-income countries (LMICs), among immunosuppressed, transplanted, and diabetic individuals, as well as COVID-19 coinfections. Intrinsic resistance and reduced susceptibility of these fungi to antifungals underscore the difficulty of current treatment strategies. This highlights the urgent need for innovative approaches against mucormycosis, including novel treatments like immunotherapies and prevention of disease by vaccines. The groundbreaking discovery of a highly conserved immunogenic epitope among mucorales species provides us with a unique opportunity for the development of a targeted vaccine with the potential of protection against tissue invasion by several mucorales species, that translated into our project aim to validate an anti-mucorales vaccine approach. This vaccine incorporates the conserved epitope formulated with immune enhancers to stimulate robust humoral immunity and protect against mucormycosis. Our goal is to evaluate whether active immunization stimulates robust protection against mucormycosis in translational mouse models that mirror at-risk populations, including diabetics, immunosuppressed individuals, and corticosteroid users. We will thoroughly study the response to active immunization, including antibodies immunogenicity characteristics, using advanced imaging techniques to monitor fungal infection progression. This rigorous testing in translational models strengthens the reliability of our findings and streamlines the foundations for clinical approaches, advancing toward much-needed effective treatments for mucormycosis, particularly in LMICs where infections are on the rise and therapeutic options unavailable.