Mucosal passive immunization with monoclonal antibodies targeting Candidalysin and hyphally-regulated surface-exposed proteins (Hyr family) attenuates vaginal C. albicans infections in mice
Description
Vulvovaginal candidiasis (VVC) is a fungal infection predominantly caused by the opportunistic pathogen Candida albicans (90%). VVC is a common infection, affecting 75% of women at least once in their lifetime. Among women affected by VVC, up to 8% experience more than four episodes per year, regarded as recurrent vulvovaginal candidiasis (RVVC). Current treatments for (R)VVC primarily rely on the use of azole antifungals, which are effective for treating isolated episodes but insufficient to prevent recurrences. Moreover, the intensive use of azoles may contribute to the development of resistance, highlighting the need for the development of alternative therapeutic strategies. Considering several arguments indicating that VVC may result from an immunopathological disorder characterized by a "neutrophil anergy" phenomenon, leading to an exacerbated inflammatory response, the objective of this project was to develop biological tools to assess the effectiveness of passive immunization as an alternative treatment for RVVC. In this study, we selected and characterized monoclonal antibodies (mAbs) directed against two targets of the hyphal infectious form of C. albicans. The prophylactic activity of the selected mAbs was then evaluated in vivo, using a murine model of VVC. The results demonstrated that intravaginal administration of the combined mAbs conferred protection against infection development, significantly reducing fungal colonization and inflammation in the vaginal environment. These findings highlight the potential efficacy of passive mucosal immunization with these mAbs in preventing VVC, providing strong proof of concept for their potential as a novel therapeutic strategy in the management of RVVC.