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Updated: Nov 3, 2025
Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Vaccine-Induced Protection in Two Murine Models of Invasive Pulmonary Aspergillosis
Emily Rayens1,2, Whitney Rabacal1, S Earl Kang3
1Center for Vaccines and Immunology, University of Georgia, Athens, GA, United States.
Abstract:
Life-threatening, invasive fungal infections (IFIs) cause over 1.5 million deaths worldwide and are a major public health concern with high mortality rates even with medical treatment. Infections with the opportunistic fungal pathogen, Aspergillus fumigatus are among the most common. Despite the growing clinical need, there are no licensed vaccines for IFIs. Here we evaluated the immunogenicity and protective efficacy of an A. fumigatus recombinant protein vaccine candidate, AF.KEX1, in experimental murine models of drug-induced immunosuppression. Immunization of healthy mice with AF.KEX1 and adjuvant induced a robust immune response. Following AF.KEX1 or sham immunization, mice were immunosuppressed by treatment with either cortisone acetate or hydrocortisone and the calcineurin inhibitor, tacrolimus. To test vaccine efficacy, immunosuppressed mice were intranasally challenged with A. fumigatus conidia (Af293) and weight and body temperature were monitored for 10 days. At study termination, organism burden in the lungs was evaluated by quantitative PCR and Gomori's methanamine silver staining. In both models of immunosuppression, AF.KEX1 vaccinated mice experienced decreased rates of mortality and significantly lower lung organism burden compared to non-vaccinated controls. The lung fungal burden was inversely correlated with the peak anti-AF.KEX1 IgG titer achieved following vaccination. These studies provide the basis for further evaluation of a novel vaccine strategy to protect individuals at risk of invasive aspergillosis due to immunosuppressive treatments.
Insights
A novel recombinant protein vaccine candidate, AF.KEX1, shows promise in protecting against invasive fungal infections caused by Aspergillus fumigatus. Vaccinated mice demonstrated reduced mortality and fungal burden in immunosuppressed models.
Area of Science:
- Mycology
- Immunology
- Vaccinology
Background:
- Invasive fungal infections (IFIs), particularly aspergillosis, pose a significant global health threat with high mortality.
- Current treatments for IFIs have limitations, and there is a critical unmet need for effective vaccines.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of a novel recombinant protein vaccine candidate, AF.KEX1, against invasive aspergillosis.
- To assess the vaccine's performance in murine models of drug-induced immunosuppression.
Main Methods:
- Mice were immunized with the AF.KEX1 vaccine candidate and adjuvant.
- Immunosuppression was induced using cortisone acetate/hydrocortisone and tacrolimus.
- Vaccine efficacy was tested by intranasal challenge with Aspergillus fumigatus conidia, monitoring survival, weight, and body temperature.
- Fungal burden in lungs was quantified using qPCR and Gomori's methanamine silver staining.
Main Results:
- AF.KEX1 immunization induced a robust immune response in healthy mice.
- Vaccinated mice showed significantly reduced mortality rates and lower fungal burden in the lungs compared to controls in both immunosuppression models.
- A strong inverse correlation was observed between anti-AF.KEX1 IgG titers and lung fungal burden.
Conclusions:
- The AF.KEX1 vaccine candidate demonstrates significant protective efficacy against invasive aspergillosis in experimental immunosuppressed models.
- These findings support the further development of AF.KEX1 as a potential vaccine strategy for individuals at risk of invasive aspergillosis.
