Work

Mannoprotein Cig1 contributes to the immunogenicity of a heat-killed F-box protein Fbp1 Cryptococcus neoformans vaccine model

Year: 2025

Type: article

Abstract: 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 a Cryptococcus neoformans mutant strain fbp1 Δ 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-killed fbp1 Δ (HK- fbp1 ) can elicit an interferon gamma (IFN-γ)-dependent Type 1 immune response and provide protection against C. neoformans and its sibling species C. gattii . However, we have yet to decipher the immunogenic factor(s) expressed by the fbp1 ∆ 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- fbp1 vaccine-mediated protection as acapsular HK- fbp1 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- fbp1 . Deletion of Cig1 in the fbp1 Δ 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 the fbp1 Δ mutant resulted in reduced protection in vaccination survival studies at lower vaccine inoculum doses compared to HK- fbp1 . In aggregate, these findings demonstrate Cig1 is an antigen contributing to the immunogenicity of HK- fbp1 that may be utilized to further optimize the HK- fbp1 fungal vaccine as a tool in the arsenal against invasive fungal infections.

Source: Infection and Immunity

DOI: 10.1128/iai.00355-25

Authors: Samantha L. Avina, Siddhi Pawar, Roshni N. Kadam, Amariliz Rivera, Chaoyang Xue

Institutions: Rutgers, The State University of New Jersey, Rutgers New Jersey Medical School

Language: English

Topic: Fungal Infections and Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases