title: Identification and characterization of Cryptococcus neoformans protein fractions that induce protective immune responses.
abstract: Cryptococcus neoformans, the main causative agent of cryptococcosis, is a fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. To date, there is no vaccine or immunotherapy approved to treat cryptococcosis. Cell- and antibody-mediated immune responses collaborate to mediate optimal protection against C. neoformans infections. Accordingly, we identified cryptococcal protein fractions capable of stimulating cell- and antibody-mediated immune responses and determined their efficacy to elicit protection against cryptococcosis. Proteins were extracted from C. neoformans and fractionated based on molecular mass. The fractions were then evaluated by immunoblot analysis for reactivity to serum extracted from protectively immunized mice and in cytokine recall assays for their efficacy to induce pro-inflammatory and Th1-type cytokine responses associated with protection. MS analysis revealed a number of proteins with roles in stress response, signal transduction, carbohydrate metabolism, amino acid synthesis, and protein synthesis. Immunization with select protein fractions containing immunodominant antigens induced significantly prolonged survival against experimental pulmonary cryptococcosis. Our studies support using the combination of immunological and proteomic approaches to identify proteins that elicit antigen-specific antibody and Th1-type cytokine responses. The immunodominant antigens that were discovered represent attractive candidates for the development of novel subunit vaccines for treatment and/or prevention of cryptococcosis.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX, USA; South Texas Center for Emerging Infectious Diseases, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chaturvedi
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lopez-Ribot
authors.forename: Floyd L
authors.initials: FL
authors.lastname: Wormley
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D002473:Cell Wall / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D003453:Cryptococcosis / Q000276:immunology / Q000517:prevention & control*; D003455:Cryptococcus neoformans / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D005656:Fungal Proteins / Q000276:immunology* / Q000302:isolation & purification; D005657:Fungal Vaccines; D008172:Lung Diseases, Fungal / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D020543:Proteome / Q000276:immunology / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination
chemical_list: D016207:Cytokines; D005656:Fungal Proteins; D005657:Fungal Vaccines; D020543:Proteome
keywords: Cryptococcosis; Cryptococcus neoformans; Cytoplasmic proteins; Microbiology; Surface proteins; Vaccination