# Active and Passive Immunization of Pan-Fungal Vaccine NXT-2 Reduces Morbidity and Mortality in an Immunosuppressed Murine Model of Candida auris Systemic Infection

## TL;DR

A pan-fungal vaccine called NXT-2 improves survival and reduces symptoms in mice infected with Candida auris, a dangerous and drug-resistant fungus.

## Contribution

NXT-2 shows efficacy against C. auris in immunosuppressed mice through both active and passive immunization.

## Key findings

- Active immunization with NXT-2 improved survival in infected mice from 13.8% to 48.4%.
- Passive immunization with NXT-2-specific IgG increased survival to 42% in infected mice.
- NXT-2 antibodies inhibited C. auris biofilm formation and enhanced fungal killing in vitro.

## Abstract

Background: Candida auris has emerged as a significant public health threat causing life-threatening systemic infections. Of particular concern is the frequency of multidrug resistance, high transmissibility, and persistence in the environment; thus, there is a need for novel strategies to prevent and treat this infection. We previously generated a “pan-fungal” vaccine candidate, NXT-2, which induces protective immunity against several invasive fungal infections. Methods: In this study, we investigated the efficacy of NXT-2 immunization against systemic C. auris infection in an immunosuppressed murine model and investigated the possible mechanisms by which NXT-2 protection is mediated in vitro. Results: Active immunization afforded significant improvement in survival and reduced morbidity in neutropenic mice challenged intravenously with C. auris compared to controls (48.4% vs. 13.8%). To assess humoral immunity in promoting protection, passive immunization with NXT-2-specific IgG to neutropenic mice prior to the challenge with C. auris resulted in significantly higher survival (42% vs. 0%) and low morbidity compared to controls. Sera from NXT-2-immunized animals inhibited biofilm formation and enhanced opsonophagocytic killing of multiple C. auris clades in vitro. Conclusions: These findings show that immunization with NXT-2 improves survival in C. auris infection and that NXT-2 antibodies promote antifungal activity in vitro and in vivo. These results extend the range of the pan-fungal NXT-2 vaccine to include protection against systemic C. auris-mediated infection and provide a rationale for the development of NXT-2 monoclonal antibodies for the treatment of C. auris infections.