[HTML][HTML] Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance

M Wüthrich, HI Filutowicz… - The Journal of clinical …, 2000 - Am Soc Clin Investig
M Wüthrich, HI Filutowicz, BS Klein
The Journal of clinical investigation, 2000Am Soc Clin Investig
Systemic fungal infections are becoming more common and difficult to treat, and vaccine
prevention is not available. Pulmonary infection with the dimorphic fungus Blastomyces
dermatitidis often progresses and requires treatment to prevent fatality. We recently created
a recombinant strain of the fungus lacking the WI-1 adhesin and pathogenicity. We show
here that administration of viable yeast of this attenuated strain vaccinates against lethal
pulmonary experimental infection due to isogenic and nonisogenic strains from diverse …
Systemic fungal infections are becoming more common and difficult to treat, and vaccine prevention is not available. Pulmonary infection with the dimorphic fungus Blastomyces dermatitidis often progresses and requires treatment to prevent fatality. We recently created a recombinant strain of the fungus lacking the WI-1 adhesin and pathogenicity. We show here that administration of viable yeast of this attenuated strain vaccinates against lethal pulmonary experimental infection due to isogenic and nonisogenic strains from diverse geographic regions. To our knowledge, this is the first example of a recombinant attenuated vaccine against fungi. The vaccine induces delayed-type hypersensitivity and polarized type 1 cytokine responses, which are linked with resistance. A cell-wall/membrane (CW/M) antigen from the vaccine strain also induces polarized and protective immune responses. Lymph node cells and CD4+ T-cell lines raised with CW/M antigen transfer protective immunity when they release type 1 cytokine IFN-γ, but not when they release IL-4, and neutralization of IFN-γ confirmed its role in vivo. Thus, by mutating a pathogenetic locus in a dimorphic fungus, we have created an attenuated vaccine strain and have begun to elucidate fungal and host elements requisite for vaccine immunity.
The Journal of Clinical Investigation