title: Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice.
abstract: Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection.
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chaturvedi
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Rumanasma S
authors.initials: RS
authors.lastname: Hameed
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wozniak
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Camaron R
authors.initials: CR
authors.lastname: Hole
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Chrissy M
authors.initials: CM
authors.lastname: Leopold Wager
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Weintraub
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Lopez-Ribot
authors.affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America; The South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Floyd L
authors.initials: FL
authors.lastname: Wormley
mesh_terms: D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003453:Cryptococcosis / Q000276:immunology*; D056285:Cryptococcus gattii / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005434:Flow Cytometry; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015151:Immunoblotting; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053719:Tandem Mass Spectrometry
chemical_list: D016207:Cytokines; D005657:Fungal Vaccines