This application proposes the innovative approach of genetic immunization to the development of fungal vaccines. The research focuses on B. dermatitides, a principal endemic mycoses of both humans and mammals of veterinary importance. The focus of the work in a 120 Kd surface protein known as WI-1 which is an immunodominant antigen of B- and T-cell responses in humans and experimental animals and is a fungal adhesin that binds to host tissues. WI-1 has been cloned and sequenced and mice immunized with this protein produce humoral and cell-mediated immune responses that protect against lethal infection. The hypothesis to be tested is that WI-1 elicits specific antibodies and T cells that collaborate in mediating protection against B. dermatitides.
Five specific aims are proposed: 1) To extend previous findings that immunization of mice with native WI-1 confers protective immunity; 2) to define the roles of antibodies, T-cells and T-cell subsets in WI-1 mediated protection; 3) To map WI-1 epitopes recognized by protective antibodies and T-cells; 4) to create and test WI-1 DNA vaccines that encode protective B and T-cell epitopes alone and together; and 5) to modify the vaccine DNA to influence antigen targeting, cellular reconstitution, and tissue immflammation to augment protection. These studies are expected to yield new insight into how antibodies and T cells collaborate in defending against pathogenic fungi and provide a model for evoking these defenses with DNA to engender protective immunity.
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