induction of broad-spectrum protective immunity against disparate cryptococcus serotypes
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2017
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Abstract
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.
| Reference Key |
dyke2017frontiersinduction
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| Authors | ;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 |
| Journal | sudebno-meditsinskaia ekspertiza |
| Year | 2017 |
| DOI |
10.3389/fimmu.2017.01359
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| URL | |
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