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Fungal and Parasitic Infections

Immunogenicity and Protective Efficacy of the WI-1 Adhesin of Blastomyces dermatitidis

Marcel Wüthrich, Wun-ling Chang, Bruce S. Klein
Marcel Wüthrich
Departments of Pediatrics, Internal Medicine, and Medical Microbiology and Immunology and the Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792
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Wun-ling Chang
Departments of Pediatrics, Internal Medicine, and Medical Microbiology and Immunology and the Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792
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Bruce S. Klein
Departments of Pediatrics, Internal Medicine, and Medical Microbiology and Immunology and the Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792
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DOI: 10.1128/IAI.66.11.5443-5449.1998
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ABSTRACT

People infected with Blastomyces dermatitidis develop strong immunity to the yeast surface adhesin WI-1, including antibody responses to the adhesive domain, a 25-amino-acid repeat, and cellular responses to the N terminus. We studied the immunogenicity of WI-1 and the ability of anti-WI-1 immune responses to protect against lethal pulmonary infection in mice. WI-1 immunization, given in Freund’s adjuvant subcutaneously in two doses 2 weeks apart, evoked delayed hypersensitivity responses in a concentration-dependent manner. Immunized mice also had anti-WI-1 antibody responses, with titers reaching an endpoint dilution of approximately 1:800,000. Anti-WI-1 immunoglobulin G (IgG) antibody subclasses were IgG1 > IgG2b > IgG2a > IgG3, indicating a mixed T helper 1 and T helper 2 immune response. In protection experiments, WI-1 immunization significantly prolonged the survival of C57BL/6 and BALB/c mice compared to controls following intranasal administration of a lethal dose of B. dermatitidis yeasts (Kaplan-Meier survival curveP values of 0.027 to 0.0002) and also protected a proportion of the animals from death due to progressive pulmonary blastomycosis. Taken together, our results suggest that administration of WI-1 raises antibody and cell-mediated immune responses, which enhance resistance against pulmonary infection with B. dermatitidis. Mechanisms of vaccine-induced resistance require further investigation.

  • Copyright © 1998 American Society for Microbiology
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Immunogenicity and Protective Efficacy of the WI-1 Adhesin of Blastomyces dermatitidis
Marcel Wüthrich, Wun-ling Chang, Bruce S. Klein
Infection and Immunity Nov 1998, 66 (11) 5443-5449; DOI: 10.1128/IAI.66.11.5443-5449.1998

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Immunogenicity and Protective Efficacy of the WI-1 Adhesin of Blastomyces dermatitidis
Marcel Wüthrich, Wun-ling Chang, Bruce S. Klein
Infection and Immunity Nov 1998, 66 (11) 5443-5449; DOI: 10.1128/IAI.66.11.5443-5449.1998
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KEYWORDS

Antigens, Fungal
Blastomyces
Blastomycosis
Fungal Proteins
Glycoproteins

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