Mucosal passive immunization with monoclonal antibodies targeting Candidalysin and Hyr proteins attenuates vaginal candidiasis in mice

Vulvovaginal candidiasis (VVC) is a prevalent fungal infection primarily caused by the opportunistic pathogen <i>Candida albicans</i>. Among women affected by VVC, up to 8% experience more than four episodes per year, regarded as recurrent vulvovaginal candidiasis (RVVC). Current treatments for VVC are effective for isolated episodes but are insufficient for preventing recurrences, highlighting the need to develop novel treatments for the management of RVVC. In this study, we explore passive immunization as a potential alternative strategy to prevent VVC. The Candidalysin toxin (Cdlys) and the parietal protein Hyr1, specifically expressed by the infectious hyphal form of <i>C. albicans</i>, were selected as targets for murine mAbs development. Anti-Cdlys and anti-Hyr mAbs were produced using the hybridoma technology and were first selected for their antigenic specificity and high affinity. The anti-Hyr1 mAb 4F3.2.1 was then selected for its efficient opsonophagocytic activity with murine macrophages, while the anti-Cdlys mAb 5E2.2.1 was selected for its strong ability to neutralize the cytolytic and pro-inflammatory effects of Candidalysin. The prophylactic activity of the mAbs was then evaluated <i>in vivo</i> in a murine model of VVC. Results demonstrated that intravaginal administration of the combined mAbs confered protection against the development of the infection, significantly reducing fungal colonization and inflammation in the vaginal environment. These findings highlight the putative efficacy of passive mucosal immunization with anti-Cdlys and anti-Hyr1 mAbs in preventing VVC, providing a strong proof of concept for their potential as novel therapeutic strategy in the management of RVVC.