<p>Fungal infections pose a major worldwide health risk, as newly emerging pathogens and the increasing spread of drug resistance are now severely challenging current therapeutic and diagnostic tools. <i>Candidozyma auris</i> embodies both of these aspects as it is an urgent threat that is resistant to several antifungal classes. The lack of effective drugs is driving the development of innovative strategies, among them monoclonal antibodies. This study investigates the in vivo and ex vivo safety and efficacy of the humanized monoclonal antibody Dia-T51, administered alone or in combination with amphotericin B (AMB), in <i>Galleria mellonella</i> model. Against <i>C. auris</i> infection, Dia-T51 demonstrated good therapeutic efficacy and provided near-complete protection when used prophylactically. The synergy between Dia-T51 and AMB observed in vitro was confirmed in vivo, resulting in enhanced larval survival and a significant reduction in fungal burden. The results strengthen the profile of Dia-T51 as a promising biological agent against fungal infections both for its standalone potential (via direct inhibition and immune-mediated mechanisms) and for its ability to amplify the efficacy of conventional antifungals.</p>

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Candidozyma auris-infected Galleria mellonella larvae: the effect of the humanized monoclonal antibody Dia-T51 and its synergy with amphotericin B

  • Tania Vanzolini,
  • Valentina Fiori,
  • Mauro Magnani

摘要

Fungal infections pose a major worldwide health risk, as newly emerging pathogens and the increasing spread of drug resistance are now severely challenging current therapeutic and diagnostic tools. Candidozyma auris embodies both of these aspects as it is an urgent threat that is resistant to several antifungal classes. The lack of effective drugs is driving the development of innovative strategies, among them monoclonal antibodies. This study investigates the in vivo and ex vivo safety and efficacy of the humanized monoclonal antibody Dia-T51, administered alone or in combination with amphotericin B (AMB), in Galleria mellonella model. Against C. auris infection, Dia-T51 demonstrated good therapeutic efficacy and provided near-complete protection when used prophylactically. The synergy between Dia-T51 and AMB observed in vitro was confirmed in vivo, resulting in enhanced larval survival and a significant reduction in fungal burden. The results strengthen the profile of Dia-T51 as a promising biological agent against fungal infections both for its standalone potential (via direct inhibition and immune-mediated mechanisms) and for its ability to amplify the efficacy of conventional antifungals.