Vaccination with Live or Heat-Killed Aspergillus fumigatus Δ sglA Conidia Fully Protects Immunocompromised Mice from Invasive Aspergillosis.
Caroline Mota FernandesTyler G NormileJoao Henrique Tadini Marilhano FabriVeronica Soares BrauerGlauber R de S AraújoSusana FrasesLeonardo NimrichterIran MalavaziMaurizio Del PoetaPublished in: mBio (2022)
Aspergillus fumigatus causes invasive aspergillosis (IA) in immunocompromised patients, resulting in high mortality rates. Currently, no vaccine formulations to promote immune protection in at-risk individuals have been developed. In this work, we deleted the sterylglucosidase-encoding gene, sglA , in Aspergillus fumigatus and investigated its role in fungal virulence and host vaccine protection. The Δ sglA mutant accumulated sterylglucosides (SGs), newly studied immunomodulatory glycolipids, and exhibited reduced hyphal growth and altered compositions of cell wall polysaccharides. Interestingly, the Δ sglA mutant was avirulent in two murine models of IA and was fully eliminated from the lungs. Both corticosteroid-induced immunosuppressed and cyclophosphamide-induced leukopenic mice vaccinated with live or heat-killed Δ sglA conidia were fully protected against a lethal wild-type A. fumigatus challenge. These results highlight the potential of SG-accumulating strains as safe and promising vaccine formulations against invasive fungal infections. IMPORTANCE Infections by Aspergillus fumigatus occur by the inhalation of environmental fungal spores called conidia. We found that live mutant conidia accumulating glycolipids named sterylglucosides are not able to cause disease when injected into the lung. Interestingly, these animals are now protected against a secondary challenge with live wild-type conidia. Remarkably, protection against a secondary challenge persists even with vaccination with heat-killed mutant conidia. These results will significantly advance the field of the research and development of a safe fungal vaccine for protection against the environmental fungus A. fumigatus.
Keyphrases
- wild type
- cell wall
- escherichia coli
- end stage renal disease
- heat stress
- high glucose
- diabetic rats
- newly diagnosed
- chronic kidney disease
- candida albicans
- human health
- ejection fraction
- pseudomonas aeruginosa
- staphylococcus aureus
- low dose
- biofilm formation
- prognostic factors
- type diabetes
- peritoneal dialysis
- intensive care unit
- oxidative stress
- atomic force microscopy
- metabolic syndrome
- cardiovascular disease
- climate change
- respiratory failure
- mass spectrometry
- high fat diet induced
- stress induced
- mechanical ventilation
- single molecule