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,
,¶
Departments of
* Pediatrics,
Pathology and Laboratory Medicine,
Internal Medicine, and
Medical Microbiology and Immunology, and
¶ Comprehensive Cancer Center, University of Wisconsin Medical School, Madison, WI 53792
Understanding fundamental mechanisms of vaccine immunity will allow
proper use and optimization of vaccines. Vaccination with a genetically
engineered, live, attenuated strain of Blastomyces
dermatitidis carrying a targeted deletion at the
BAD1 locus confers sterilizing immunity against
experimental lethal pulmonary infection. We found in this study that
T cells are requisite for durable vaccine immunity, whereas
other T and B cells are dispensable. In immune-competent animals,
CD4+ T-cell derived cytokines TNF- and IFN-
mediate
vaccine immunity. Surprisingly, these factors are dispensable in
immune-deficient animals, which rely on alternate mechanisms for robust
vaccine immunity, yet still require O2-
production rather than generation of NO. Our results clarify the
cellular and molecular bases behind the first genetically engineered
fungal vaccine. They also illustrate a sharp difference in vaccine
mechanisms between immune-competent and immune-deficient hosts, which
underscores the plasticity of residual immune elements in compromised
hosts, and points to the feasibility of developing vaccines against
invasive fungal infection in this fast growing patient
population.
This article has been cited by other articles:
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  J. Xue, X. Chen, D. Selby, C.-Y. Hung, J.-J. Yu, and G. T. Cole A Genetically Engineered Live Attenuated Vaccine of Coccidioides posadasii Protects BALB/c Mice against Coccidioidomycosis Infect. Immun., August 1, 2009; 77(8): 3196 - 3208. [Abstract] [Full Text] [PDF]
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M. Wuthrich, H. I. Filutowicz, H. L. Allen, G. S. Deepe, and B. S. Klein V{beta}1+ J{beta}1.1+/V{alpha}2+ J{alpha}49+ CD4+ T Cells Mediate Resistance against Infection with Blastomyces dermatitidis Infect. Immun., January 1, 2007; 75(1): 193 - 200. [Abstract] [Full Text] [PDF]
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 M. Wuthrich, P. L. Fisette, H. I. Filutowicz, and B. S. Klein Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to Blastomyces dermatitidis J. Immunol., May 1, 2006; 176(9): 5538 - 5547. [Abstract] [Full Text] [PDF]
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M. Wuthrich, T. Warner, and B. S. Klein CD28 Is Required for Optimal Induction, but Not Maintenance, of Vaccine-Induced Immunity to Blastomyces dermatitidis Infect. Immun., November 1, 2005; 73(11): 7436 - 7441. [Abstract] [Full Text] [PDF]
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M. Wuthrich, T. Warner, and B. S. Klein IL-12 Is Required for Induction but Not Maintenance of Protective, Memory Responses to Blastomyces dermatitidis: Implications for Vaccine Development in Immune-Deficient Hosts J. Immunol., October 15, 2005; 175(8): 5288 - 5297. [Abstract] [Full Text] [PDF]
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T. T. Brandhorst, M. Wuthrich, B. Finkel-Jimenez, T. Warner, and B. S. Klein Exploiting Type 3 Complement Receptor for TNF-{alpha} Suppression, Immune Evasion, and Progressive Pulmonary Fungal Infection J. Immunol., December 15, 2004; 173(12): 7444 - 7453. [Abstract] [Full Text] [PDF]
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 M. Wuthrich, H. I. Filutowicz, T. Warner, G. S. Deepe Jr., and B. S. Klein Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells: Implications for Vaccine Development in Immune-deficient Hosts J. Exp. Med., June 2, 2003; 197(11): 1405 - 1416. [Abstract] [Full Text] [PDF]
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