Mannoprotein Cig1 contributes to the immunogenicity of a heat-killed F-box protein Fbp1vaccine model.

Abstract

Currently, no fungal vaccine exists for clinical use, while fungal infections are responsible for over 1.5 million deaths every year. Our previous studies identified amutant strainΔ as a potential vaccine candidate. This strain contains deletion of the F-box protein Fbp1, a key subunit of the SCF E3 ligase complex necessary for ubiquitin-mediated proteolysis. Vaccination with heat-killedΔ (HK-) can elicit an interferon gamma (IFN-γ)-dependent Type 1 immune response and provide protection againstand its sibling species. However, we have yet to decipher the immunogenic factor(s) expressed by the∆ mutant that are responsible for the induction of the protective immune response. In this study, we have identified that the capsule plays an important role in HK-vaccine-mediated protection as acapsular HK-cells showed diminished protection against wild-type challenge. Additionally, our studies have shown that Cytokine Inducing Glycoprotein 1 (Cig1), a GPI-anchored mannoprotein, is regulated by Fbp1 and contributes to the immunogenicity of HK-. Deletion of Cig1 in theΔ background resulted in decreased recruitment of antifungal effector T cells and diminished production of protective inflammatory cytokines by the host. Furthermore, loss of Cig1 in theΔ mutant resulted in reduced protection in vaccination survival studies at lower vaccine inoculum doses compared to HK-. In aggregate, these findings demonstrate Cig1 is an antigen contributing to the immunogenicity of HK-that may be utilized to further optimize the HK-fungal vaccine as a tool in the arsenal against invasive fungal infections.