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 th e N terminus. We studied the immunogenicity of WI-1 and the ability of anti-WI-1 immune responses to protect against lethal pulmonary infect ion in mice. WI-1 immunization, given in Freund's adjuvant subcutaneou sly in two doses 2 weeks apart, evoked delayed hypersensitivity respon ses in a concentration-dependent manner. Immunized mice also had anti- WI-l antibody responses,,vith titers reaching an endpoint dilution of approximately 1:800,000, anti-WI-1 immunoglobulin G (IgG) antibody sub classes were IgG1 > IgG2b > IgG2a > IgG3, indicating a mixed T helper 1 and T helper 2 immune response. In protection experiments, WI-1 immu nization significantly prolonged the survival of C57BL/6 and BALB/c mi ce compared to controls following intranasal administration of a letha l 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 fr om death due to progressive pulmonary blastomycosis, Taken together, o ur results suggest that administration of WI-l raises antibody and cel l-mediated immune responses, which enhance resistance against pulmonar y infection with B. dermatitidis, Mechanisms of vaccine-induced resist ance require further investigation.