CANDIDA ALBICANS PROTECTIVE EPITOPES

描述(改编自申请人的摘要)： 年血源性播散性和皮肤黏膜念珠菌病继续上升 与此同时，免疫功能低下的人数也在不断增加。几个 念珠菌可引起念珠菌病，但白色念珠菌是最常见的 这种情况普遍存在，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 播散性念珠菌病，尽管较早的论文建议抗体 事实上，它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保护性的。免疫的小鼠 白色念珠菌细胞表面磷脂蛋白(PMP)可产生保护性 抗体。分离到一株能与之结合的单抗(MAb B6.1)。 PMP中的β-1，2-三甘露糖和这种单抗增强了正常人的抵抗力 和中性粒细胞减少的小鼠对血行播散性念珠菌病。为了增强 这些抗体的进一步发展申请人建议使用 噬菌体展示文库用于分离一组在结构上 模拟保护性碳水化合物表位，并具有不同的结合 与单抗B6.1的亲和力。这些多肽将用于测试 假设多肽模拟物可以诱导抗体反应来保护 抗小鼠血源性播散性念珠菌病。计划是1) 从噬菌体展示文库中选择与 MAb B6.1；2)利用序列数据鉴定一个多肽模拟物家族 基于它们与单抗B6.1的相对结合亲和力；3)证明 这种多肽模拟物可以诱导产生识别 白念珠菌碳水化合物表位；以及4)确定潜在的保护作用 抗-C值。该多肽免疫小鼠的白念珠菌反应 模仿学。

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.