CANDIDA ALBICANS PROTECTIVE EPITOPES

描述（改编自申请人摘要）： 血行播散性和粘膜皮肤念珠菌病继续上升， 与免疫功能低下的人数量的增加相平行。 几 念珠菌属的12个种可引起念珠菌病，但C.白色念珠菌是最 这一现象普遍存在，而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起作用， 尽管较早的论文认为抗体 事实上，它起到了保护的作用。 最近的研究表明， 正确的特异性事实上是保护性的。 免疫小鼠 C.白念珠菌细胞表面磷酸甘露糖蛋白（PMP）可产生保护性 抗体的 分离出一种单克隆抗体（MAb B6.1）， PMP中的β-1，2-三甘露糖，这种MAb提高了正常 和血小板减少小鼠对血行播散性念珠菌病的影响。 加强 这些抗体的进一步发展，申请人建议使用 噬菌体展示文库以分离结构上 模拟保护性碳水化合物表位， 与MAb B6.1的亲和力。 这些肽将可用于测试 假设肽模拟物可以诱导抗体应答， 小鼠抗血行播散性念珠菌病。 计划是1） 从噬菌体展示文库中选择特异性结合联合收割机的克隆 MAb B6.1; 2）使用序列数据鉴定肽模拟物家族 基于它们与MAb B6.1的相对结合亲和力; 3）为了证明 肽模拟物可以诱导抗体的产生， C.白色念珠菌碳水化合物表位;和4）确定潜在的保护性 抗C值。 针对肽免疫的小鼠的白色念珠菌应答 拟态

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.