Candida albicans Surface Antigens

描述(申请人提供)：各种形式的念珠菌病困扰着我们的 社会，但我们过去几年的研究表明疫苗是有希望的 针对这种机会性真菌疾病的开发和抗体策略。 我们已经在一定程度上确定了抗体保护的机制。 血源性播散性念珠菌病，但需要进一步研究 完成我们对抗体保护机制的理解 防止阴道感染。我们已经在结构上定义了键的最小 低聚甘露糖苷抗体保护实验动物的表位 对经血液传播和阴道传播的念珠菌病，但 对表位的完整定义应该会导致更理想的疫苗 配方。我们知道一种没有适当蛋白质的低聚糖苷 携带者不会引起保护性抗体反应，因此我们建议 识别可能具有载体和诱导物双重作用的细胞壁蛋白 抗蛋白质保护性反应。这些研究还应该导致 对白色念珠菌中磷脂蛋白复合体功能的认识 细胞壁。这些不同的调查将通过履行 五个具体目标：1.扩大对保护的研究 抗体/补体依赖机制参与免疫保护 通过确定整个血源性播散性念珠菌病 补体级联是必要的，抗体是否具有保护性 缺乏正常的中性粒细胞和巨噬细胞功能。2.确定是否 针对阴道感染的抗体保护包括补体。3.确定 如果识别β-1，2-甘露三糖和甘露三糖的双特异性抗体 吞噬细胞上的补体受体具有保护性，不需要血清 作为保护的补充。4.确定单抗识别的完整表位 B6.1(IgM)和C3.1(IgG3)。5.鉴定与磷甘露聚糖N-连接的蛋白质 显示β-1，2-甘露三糖的络合物，确定可能的结合物 磷甘露聚糖疫苗配方的合作伙伴(载体蛋白)为 在我们的P01项目上开发，并产生突变体以启动对 这些蛋白质的功能。

DESCRIPTION (provided by applicant): Various forms of candidiasis plague our society, but our research over the past few years shows promise of vaccine development and antibody strategies against this opportunistic fungal disease. We have determined, in part, mechanisms of antibody protection against hematogenously disseminated candidiasis, but further studies are necessary to complete our understanding of mechanisms by which the antibodies protect against vaginal infection. We have structurally defined the key minimal oligomannoside epitope against which antibodies protect experimental animals against both hematogenously disseminated and vaginal forms of candidiasis, but a complete definition of the epitope should lead to more ideal vaccine formulations. We know that an oligomannoside without an appropriate protein carrier will not induce a protective antibody response, hence we propose to identify cell wall proteins that may serve a dual role as carrier and inducer of anti-protein protective responses. These studies should also lead to insights into the function of phosphomannoprotein complexes in Candida albicans cell walls. These various investigations will proceed by fulfillment of the following five specific aims: 1. Extend the studies on protective antibody/complement-dependency mechanisms involved in protection against hematogenously disseminated candidiasis by determining whether the entire complement cascade is necessary and whether the antibodies are protective in the absence of normal neutrophil and macrophage functions. 2. Determine whether antibody protection against vaginal infection involves complement. 3. Determine if bispecific antibodies that recognize both the beta-1,2-mannotriose and complement receptor on phagocytes are protective and do not require serum complement for protection. 4. Determine the complete epitope recognized by MAbs B6.1 (IgM) and C3.1 (IgG3). 5. Identify proteins N-linked to the phosphomannan complexes that display the beta-1,2-mannotriose, identify possible conjugate partners (carrier protein) for the phosphomannan vaccine formulation being developed on our P01 project and produce mutants to initiate studies into the function of these proteins.