PROTECTIVE IMMUNE RESPONSES TO BLASTOMYCES DERMATITIDIS

描述（改编自申请人摘要）：本申请提出 利用基因免疫技术开发真菌 疫苗。 研究的重点是B。皮炎，一种主要的地方病 人和哺乳动物的重要兽医真菌病。 的焦点 在120 Kd的表面蛋白质WI-1中的工作， 人和实验性B和T细胞应答免疫显性抗原 是一种与宿主组织结合的真菌粘附素。 WI-1已经 克隆和测序，用这种蛋白免疫的小鼠产生体液免疫。 和细胞介导的免疫反应，保护免受致命感染。 待检验的假设是WI-1可激发特异性抗体，T 在介导对B的保护中合作的细胞。皮炎。 提出了五个具体目标：1）扩展以前的研究结果， 用天然WI-1免疫小鼠赋予保护性免疫; 2） 定义抗体、T细胞和T细胞亚群在WI-1介导的免疫应答中的作用。 3）定位保护性抗体识别的WI-1表位， T细胞; 4）产生和测试编码保护性B的WI-1 DNA疫苗 和T细胞表位单独和一起;和5）修饰疫苗DNA， 影响抗原靶向、细胞重建和组织 免疫增强保护 这些研究预计将产生 关于抗体和T细胞如何合作防御 病原性真菌，并提供了一个模型，以唤起这些防御与DNA， 产生保护性免疫。

DESCRIPTION (Adapted from applicant's abstract): 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.