Monoclonal Antibody-Based Therapies for Disseminated Candidiasis
Technical Report,15 May 2018,14 May 2019
Louisiana State University System New Orleans United States
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The goal of this proposal is to develop and establish preclinical proof-of-concept for the first universal therapeutic antibodies that protect against disseminated candidiasis caused by all the medically important Candida species. A panel of functional monoclonal antibodies mAbs protect immunocompetent and immunocompromised mice against disseminated candidiasis have been identified. Uniquely, these protective mAbs target three universal peptide epitopes UP1, UP2 and UP3 expressed 91-100 by all the medically important Candida species, including C. auris. Furthermore,immunocompromised murine models of disseminated infection by C. tropicalis, C. glabrata, C. parapsilosis and C. krucei have been successfully established, which closely mimic the immunocompromised patient situation in clinical settings. These mouse models will be used in proposed study and prove valuable for evaluating therapies to control Candida infections. The hypothesis to be tested is that novel mAb-based therapy would 1 target multiple antigenic epitopes toachieve the greatest efficacy as compared to single mAb treatment, and 2 be composed of epitopes that are homologous among medically relevant species of Candida such that universal protection against Candida infection could be achieved, and 3 have synergyenhanced efficacy when combined with conventional antimicrobial drugs against disseminated candidiasis.
- Medicine and Medical Research