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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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    Fig. 1.

    Immunization with WI-1 induces delayed-type hypersensitivity responses in a concentration-dependent manner. Groups of three C57BL/6 mice were immunized with various doses of WI-1 or live yeast according to the protocol described in Materials and Methods. Mice were tested 2 weeks after the second immunization for delayed-type hypersensitivity by administration of 10 μg of WI-1 in saline into one footpad and saline alone into the other footpad. Measurements were taken 24 h later. Error bars represent standard errors of the mean.

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    Fig. 2.

    Anti-WI-1 IgG subclasses in four C57BL/6 mice per group immunized with either 100 μg of WI-1, 106 heat-killed yeasts (HK Yst), or 4 × 104 live yeast (Live Yst) subcutaneously (A) and three C57BL/6 mice per group immunized with various doses of WI-1 as shown (B). In each experiment, sera were obtained 2 weeks after the second immunization and analyzed for anti-WI-1 IgG subclass by ELISA. Error bars indicate standard error of the mean. OD, optical density. NMS, normal mouse serum.

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    Fig. 3.

    Protective efficacy of WI-1 immunization against lethal pulmonary blastomycosis. Groups of C57BL/6 mice were immunized subcutaneously either with 100 μg of WI-1 or with BSA according to the protocol described in Materials and Methods. Two weeks after a second immunization, the mice were challenged with a lethal dose of 104B. dermatitidis ATCC 60636 yeasts and observed for survival. Kaplan-Meier survival curves were generated for WI-1-immunized mice and control mice during an observation interval of 30 days after experimental infection.

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    WI-1 prolongs the survival of mice challenged with a lethal dose of B. dermatitidisa

    ExptMouse strainsGroup (n)Mean survival (days)% Survival at 30 days postinfection (no. of mice that survived/total no. of mice)Significanceb (P)
    1C57BL/6WI-1 (8)2875 (6/8)0.0002
    BSA (8)180 
    2C57BL/6WI-1 (11)2127 (3/11)0.0002
    BSA (14)150 
    3C57BL/6WI-1, 200 μg (12)170 0.009
    WI-1, 10 μg (12)130 
    4BALB/cWI-1 (8)2125 (2/8)0.027
    BSA (8)160 
    5C57BL/6Histo/WI-1 (7)2529 (2/7)0.026†
    Histo alone (15)200 0.045‡
    Unimmunized (10)1810 (1/10)
    • ↵a Summary of five separate protection experiments performed in C57BL/6 mice and BALB/c mice. C57BL/6 or BALB/c mice were immunized with WI-1 or BSA according to the protocol described in Materials and Methods. Mice were observed for survival after intranasal infection with a lethal dose of 104 ATCC 60636 yeasts. In experiment 5, mice were intranasally infected twice (1 month apart) with a sublethal dose of either H. capsulatum184 AS ura 5-11 expressing WI-1 off the telomeric, extrachromosomal plasmid pMAD93/WI-1 (Histo/WI-1) or the control strain transformed with plasmid pMAD93 lacking WI-1 (Histo alone). These immunized and control mice were challenged intranasally with a lethal dose of 104 ATCC 26199 yeasts 2 weeks after the second immunization and monitored for survival.

    • ↵b Two-sided P value. †, comparison of Histo/WI-1 group versus Histo alone group; ‡, comparison of Histo/WI-1 group versus unimmunized group.

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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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