Immunogenicity and protective efficacy of the WI-1 adhesin of Blastomyces dermatitidis.
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 curve P 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.
Departments of Pediatrics, Internal Medicine, Medical Microbiology and Immunology, Comprehensive Cancer Center, University of Wisconsin Medical School, Hospitals and Clinics, Madison, WI 53792, USA.
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Wüthrich
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Chang
B S
BS
Klein
D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D000946:Antigens, Fungal / Q000276:immunology*; D001758:Blastomyces / Q000276:immunology*; D001759:Blastomycosis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D005656:Fungal Proteins / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins