IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

隐孢子虫仍然是一个主要的原因，持续性牙周病 艾滋病患者中。 艾滋病患者的隐孢子虫病会因以下因素而加重： 缺乏有效的化疗集体研究有 然而，提供的证据表明，超免疫多克隆抗体 口服制剂或单克隆抗体可减轻疾病的严重程度。 我们 已经专注于单克隆抗体（MAb）方法来治疗阿拉齐斯， 处理，因为这些试剂具有均匀性，可以在 可以无限量地、特异性地靶向重要的寄生虫抗原， 使用体外和体内模型系统验证疗效，并基于 到目前为止的结果可能有助于预防或治疗 战略布局 在这份为期2年的最终提案中，我们将继续采用综合方法 完成临床前的工作， 旨在预防和治疗隐孢子虫病。 核心设施B， 亚利桑那州将为所有项目提供寄生虫研究。 项目1和 2在亚利桑那州将广泛互动，以确定最佳配方的 先前产生的针对裂殖子的致神经瘤单克隆抗体， 子孢子阶段分别和定义抗体的机制- 介导的中和。 北卡罗来纳州的项目3将使用 重组策略，以生产和表征抗 保护性抗原可用于控制 肠外隐孢子虫病 北卡罗来纳州的核心C 大学将进行最终的临床前测试和验证， 抗肠内和肠外寄生虫的MAb 免疫缺陷小鼠的隐孢子虫病。 整个工程将 Arizona（Core A） 在完成这些目标后， 业务合作伙伴已签订具有约束力的协议，承担全部 负责临床前开发和临床试验。

Cryptosporidum parvum remains a major cause of persisten diarrheal illneess among AIDS patients. Crytosportidiosis in AIDS patients is exacerbated by the absecnce of an effective chemotherapy. Collective studi8es have provided evidence,however, that hyperimmune polyclonal antibody preparations or MAbs given orally may reduce the severity of diesease. We have focused on a monoclonal antibody (MAb) approach to prophylazis and treatment because these reagents have uniformity, can be produced in unlimited quantity, specificaly target important parasite antigens, can be validated for efficacy using in vitro and in vivo model systems, and based on results to date are likely to be useful in preventive or treatment strategies. In this 2 year final proposal we will continue with an integrated approach to complete pre-clinical efforts in developing an immunologic strategy aimed for preventing and treating crytosporitdiosis. Core facility B at Arizona will provide parasites for study to all projects. Projects 1 and 2 at Arizona will interact extensively to define optimal formulations of previously produced neurtalizing MAbs ddirected against the merozoite the sporozoite stages respectively and to define mechanisms of antibody- mediated neutralization. Project 3 at North Carolina State will use recombinant strategies to produce and characterize dimeric lgA MAbs agaisnt protective antigens which can be used in a strategy to control extraintestinal cryptosporidiosis. COre C at North Carolina State University will conduct the final pre-clinical testing and validation of MAbs for efficacy against peristent intestinal and extraintestinal cryptosporidiosis in immunodeficient mice. The entire project will be directed by Arizona (Core A). Upon completion of these objectives the business partner has entered a binding agreement to assume full responsibility for pre-clinical development and clinical trials.