CANDIDA ALBICANS PROTECTIVE EPITOPES

白色念珠菌保护表位

• 批准号: 2887479
• 负责人: Jim E. Cutler
• 金额: $ 19.7万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887479
• 关键词: Candida albicans; antibody formation; antibody specificity; carbohydrate structure; chemical binding; fungal antigens; genetic library; laboratory mouse; microorganism immunology; molecular cloning; monoclonal antibody; peptide structure; protein sequence

DESCRIPTION (Adapted from applicant's abstract): The incidence of hematogenous disseminated and mucocutaneous candidiasis continues to rise in parallel with the increasing number of immunocompromised peopole. Several species of Candida can cause candidiasis but C. albicans is the most prevalent and there is still confusion regarding host defence mechanisms. For years the prevailing dogma is that antibodies do not play a role against disseminated candidiasis even though older papers suggested that antibodies did, in fact, play a role in protection. Recent work shows that antibodies of the correct specificity are in fact protective. Mice immunized against C. albicans cell surface phosphomannoprotein (PMP) can produce protective antibodies. A monoclonal antibody (MAb B6.1) was isolated that reacts with a beta-1,2-trimannose in the PMP and this MAb heightens resistance of normal and neutropenic mice to hematogenous disseminated candidiasis. To enhance further development of these antibodies the applicant proposes to use a phage display library to isolate a family of peptides that structurally mimic the protective carbohydrate epitope and have varying binding affinities to MAb B6.1. These peptides will be useful in testing the hypothesis that peptide mimetics can induce antibody responses that protect mice against hematogenous disseminated candidiasis. The plan is to 1) select clones from a phage display library that specifically combine with MAb B6.1; 2) use the sequence data to identify a family of peptide mimetics based on their relative binding affinities to MAb B6.1; 3) To demonstrate that the peptide mimetics can induce production of antibodies that recognize C. albicans carbohydrate epitopes; and 4) determine the potential protective value of anti-C. albicans responses of mice immunized against the peptide mimetics.

描述（改编自申请人的摘要）：发生率 血行播散性和皮肤粘膜念珠菌病继续增加 与此同时，免疫功能低下人群的数量也在不断增加。 一些 念珠菌属可引起念珠菌病，但最常见的是白色念珠菌 普遍存在，并且关于宿主防御机制仍然存在混乱。 多年来，流行的教条是抗体不会发挥作用 传播念珠菌病，尽管较早的论文表明抗体 事实上，确实起到了保护作用。 最近的研究表明，抗体 正确的特异性实际上是有保护作用的。 小鼠已免疫 白色念珠菌细胞表面磷酸甘露糖蛋白（PMP）可产生保护作用 抗体。 分离出一种单克隆抗体 (MAb B6.1)，它与 PMP 中的 β-1,2-三甘露糖，这种单克隆抗体可增强正常细胞的抵抗力 和中性粒细胞减少小鼠发生血行播散性念珠菌病。 增强 申请人建议使用这些抗体的进一步开发 噬菌体展示文库，用于分离结构上的肽家族 模仿保护性碳水化合物表位并具有不同的结合 与 MAb B6.1 的亲和力。 这些肽可用于测试 假设肽模拟物可以诱导抗体反应，从而保护 小鼠对抗血行播散性念珠菌病。 计划是 1) 从噬菌体展示库中选择专门与 单克隆抗体B6.1； 2) 使用序列数据来识别肽模拟物家族 基于它们与 MAb B6.1 的相对结合亲和力； 3）展示 肽模拟物可以诱导产生识别的抗体 C.白色念珠菌碳水化合物表位； 4) 确定潜在的保护 抗值 C. 针对该肽免疫的小鼠的白色念珠菌反应 模仿者。