PROTECTIVE IMMUNE RESPONSES TO BLASTOMYCES DERMATITIDIS

描述(改编自申请人的摘要)：本申请提出 基因免疫在真菌发育中的创新途径 疫苗。这项研究的重点是皮炎杆菌，一种主要的地方病。 在兽医上具有重要意义的人类和哺乳动物的真菌病。的关注点 在一种名为WI-1的120kD表面蛋白中所做的工作是一种 人类和实验性B细胞和T细胞反应的免疫优势抗原 是一种真菌粘附素，与宿主组织结合。Wi-1已经 该蛋白克隆测序及免疫小鼠产生体液 以及细胞介导的免疫反应，以防止致命感染。 需要检验的假设是，WI-1会引起特异性抗体和T细胞 协同调节对皮炎杆菌的保护作用的细胞。 提出了五个具体目标：1)扩大先前的调查结果 用原生WI-1免疫小鼠可产生保护性免疫；2) 明确抗体、T细胞和T细胞亚群在WI-1介导中的作用 保护；3)绘制保护性抗体识别的WI-1表位图； T细胞；4)创造和测试编码保护性B细胞的WI-1 DNA疫苗 和T细胞表位；以及5)将疫苗DNA修饰为 影响抗原靶向、细胞重建和组织 注射以加强保护。这些研究预计将产生 抗体和T细胞如何协同防御疾病的新见解 病原真菌并提供了一种用DNA激发这些防御系统的模型 产生保护性免疫力。

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.