IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

隐孢子虫是一个主要的原因，持续性牙周病 艾滋病患者中。 目前的估计是，15 - 20%的艾滋病患者 患者最终可能会感染这种疾病。 真实数量 然而，患者目前尚不清楚，可能报告不足。 艾滋病患者的隐孢子虫病问题因 缺乏有效的化疗。 最近的研究提供了 然而，有证据表明，口服超免疫抗体制剂 可以降低疾病的严重程度。 根据这个想法，我们 已经专注于单克隆抗体（MAb）预防方法， 处理，因为这些试剂具有均匀性，可以在 无限量，可以识别重要的寄生虫抗原， 使用体外和体内模型系统进行详尽测试，并且可以 有助于开辟替代预防或治疗策略。 在这个持续的计划项目提案中，我们将重点关注 开发免疫策略的综合方法， 预防和治疗艾滋病患者的隐孢子虫病。 核心 将建立设施，向所有人提供寄生虫试剂， 项目（9001亚利桑那州），提供一种测试MAbs有用的手段 针对肠内和肠外隐孢子虫病， 通过使用免疫缺陷小鼠的保护性抗原和反应 (9002华盛顿）。 亚利桑那州的项目1和项目2将广泛互动 并重点开展与识别和定性中和有关的工作 分别针对裂殖子和子孢子阶段的单克隆抗体。 华盛顿的项目3将重点关注重组策略， 产生和表征子孢子和裂殖子蛋白， 诱导抗C.小的 亚利桑那州的项目4将 重点在于获得抗子孢子抗原的鼠二聚体IgA单抗 已知是中和敏感的，并且可以用于策略中， 来控制肠外隐孢子虫病 整个工程将 由Arizona执导。

Cryptosporidium parvum is a major cause of persistent diarrheal illness among AIDS patients. Current estimates are that from 15-20% of AIDS patients may eventually contract this infection. The true number of such patients, however, is currently unknown and likely to be underreported. The problem with cryptosporidiosis in AIDS patients is exacerbated by the absence of an effective chemotherapy. Recent studies have provided evidence, however, that hyperimmune antibody preparations given orally may reduce the severity of disease. Following through on this idea, we have focused on a monoclonal antibody (MAb) approach to prophylaxis and treatment because these reagents have uniformity, can be produced in unlimited quantity, can identify important parasite antigens, can be exhaustively tested using in vitro and in vivo model systems, and may be useful in opening up alternate preventive or treatment strategies. In this continuing Program Project proposal we will focus on an integrated approach to developing an immunologic strategy aimed at preventing and treating cryptosporidiosis in the AIDS patient. Core facilities will be established to provide parasite reagents to all projects (9001 Arizona), to provide a means of testing MAbs useful against intestinal and extraintestinal cryptosporidiosis, and to identify protective antigens and responses through use of immune deficient mice (9002 Washington). Projects 1 and 2 at Arizona will interact extensively and focus on work relating to identifying and characterizing neutralizing MAbs directed against the merozoite and sporozoite stages respectively. Project 3 at Washington will focus on recombinant strategies aimed at producing and characterizing sporozoite and merozoite proteins that induce protective responses against C. parvum. Project 4 at Arizona will focus on deriving murine dimeric IgA MAbs against antigens of sporozoites known to be neutralization sensitive and which can be used in a strategy to control extraintestinal cryptosporidiosis. The entire project will be directed by Arizona.