Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes
Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neof...
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| Format: | Article |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01359/full |
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| author | Marley C. Caballero Van Dyke Marley C. Caballero Van Dyke Ashok K. Chaturvedi Ashok K. Chaturvedi Sarah E. Hardison Sarah E. Hardison Chrissy M. Leopold Wager Chrissy M. Leopold Wager Natalia Castro-Lopez Natalia Castro-Lopez Camaron R. Hole Camaron R. Hole Karen L. Wozniak Karen L. Wozniak Floyd L. Wormley Floyd L. Wormley |
| author_facet | Marley C. Caballero Van Dyke Marley C. Caballero Van Dyke Ashok K. Chaturvedi Ashok K. Chaturvedi Sarah E. Hardison Sarah E. Hardison Chrissy M. Leopold Wager Chrissy M. Leopold Wager Natalia Castro-Lopez Natalia Castro-Lopez Camaron R. Hole Camaron R. Hole Karen L. Wozniak Karen L. Wozniak Floyd L. Wormley Floyd L. Wormley |
| author_sort | Marley C. Caballero Van Dyke |
| collection | DOAJ |
| description | Cryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide “proof-of-concept” for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus. |
| first_indexed | 2024-12-12T15:16:58Z |
| format | Article |
| id | doaj.art-8a156071758c4a378bfe53d5b02194d2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T15:16:58Z |
| publishDate | 2017-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-8a156071758c4a378bfe53d5b02194d22022-12-22T00:20:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01359280656Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus SerotypesMarley C. Caballero Van Dyke0Marley C. Caballero Van Dyke1Ashok K. Chaturvedi2Ashok K. Chaturvedi3Sarah E. Hardison4Sarah E. Hardison5Chrissy M. Leopold Wager6Chrissy M. Leopold Wager7Natalia Castro-Lopez8Natalia Castro-Lopez9Camaron R. Hole10Camaron R. Hole11Karen L. Wozniak12Karen L. Wozniak13Floyd L. Wormley14Floyd L. Wormley15Department of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesDepartment of Biology, The University of Texas at San Antonio, San Antonio, TX, United StatesThe South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United StatesCryptococcosis is a fungal disease caused by multiple Cryptococcus serotypes; particularly C. neoformans (serotypes A and D) and C. gattii (serotypes B and C). To date, there is no clinically available vaccine to prevent cryptococcosis. Mice given an experimental pulmonary vaccination with a C. neoformans serotype A strain engineered to produce interferon-γ, denoted H99γ, are protected against a subsequent otherwise lethal experimental infection with C. neoformans serotype A. Thus, we determined the efficacy of immunization with C. neoformans strain H99γ to elicit broad-spectrum protection in BALB/c mice against multiple disparate Cryptococcus serotypes. We observed significantly increased survival rates and significantly decreased pulmonary fungal burden in H99γ immunized mice challenged with Cryptococcus serotypes A, B, or D compared to heat-killed H99γ (HKH99γ) immunized mice. Results indicated that prolonged protection against Cryptococcus serotypes B or D in H99γ immunized mice was CD4+ T cell dependent and associated with the induction of predominantly Th1-type cytokine responses. Interestingly, immunization with H99γ did not elicit greater protection against challenge with the Cryptococcus serotype C tested either due to low overall virulence of this strain or enhanced capacity of this strain to evade host immunity. Altogether, these studies provide “proof-of-concept” for the development of a cryptococcal vaccine that provides cross-protection against multiple disparate serotypes of Cryptococcus.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01359/fullCryptococcus neoformansCryptococcus gattiicryptococcosishost–fungal interactionfungal vaccinesfungal immunology |
| spellingShingle | Marley C. Caballero Van Dyke Marley C. Caballero Van Dyke Ashok K. Chaturvedi Ashok K. Chaturvedi Sarah E. Hardison Sarah E. Hardison Chrissy M. Leopold Wager Chrissy M. Leopold Wager Natalia Castro-Lopez Natalia Castro-Lopez Camaron R. Hole Camaron R. Hole Karen L. Wozniak Karen L. Wozniak Floyd L. Wormley Floyd L. Wormley Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes Frontiers in Immunology Cryptococcus neoformans Cryptococcus gattii cryptococcosis host–fungal interaction fungal vaccines fungal immunology |
| title | Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes |
| title_full | Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes |
| title_fullStr | Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes |
| title_full_unstemmed | Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes |
| title_short | Induction of Broad-Spectrum Protective Immunity against Disparate Cryptococcus Serotypes |
| title_sort | induction of broad spectrum protective immunity against disparate cryptococcus serotypes |
| topic | Cryptococcus neoformans Cryptococcus gattii cryptococcosis host–fungal interaction fungal vaccines fungal immunology |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01359/full |
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