IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

隐孢子虫可能会导致艾滋病患者持续性肺部疾病 患者 受感染的艾滋病患者人数很可能是 被低估了 不幸的是，化疗治疗的尝试 到目前为止都失败了。 最近的研究表明， 超免疫抗体制剂可以显著降低 疾病 通过这个想法，我们计划专注于单克隆抗体。 抗体（Mab）的方法来预防和治疗，因为这些试剂 具有一致性，可以无限量生产，可以识别 重要的寄生虫抗原，因此可能开辟了替代 治疗策略，并可以使用适当的 动物模型系统。 由于这些单克隆抗体很可能在最大限度地抑制细胞增殖的情况下最有效， 许多生命周期阶段可以中和，我们将专注于生产 中和抗裂殖子孢子和性期的单克隆抗体 向所有项目提供隐孢子虫的Ioqa分离株， 核心设施 这些单克隆抗体活性将被单独测试， 或组合使用免疫活性新生小鼠模型， 中和或预防。 此外，我们还将测试 这些单克隆抗体通过使用免疫活性的新生小鼠治疗模型 免疫受损小鼠模型的预防和治疗，并通过使用 改进或新开发的体外培养物，以研究阶段特异性 中和 每个项目都将描述和隔离 相关阶段特异性抗原，并将其用于 生产牛-鼠和人单克隆抗体作为替代治疗 控制艾滋病患者感染的策略。 因为有些 这些抗原可能难以识别或产生，我们将依赖于 cDNA和基因组文库构建及合适文库的使用 表达载体。 单克隆抗体显示预防性和 治疗效果和保证临床试验最终将是 大量生产。

Cryptosporidium parvum may produce persistent diarrheal illness in AIDS patients. The number of infected AIDS patients is likely to be underreported. Unfortunately, chemotherapeutic attempts at treatment have so far failed. Recent studies have provided evidence that treatment with hyperimmune antibody preparations may significantly reduce the severity of disease. Following through on this idea, we plan to focus on monoclonal antibody (Mab) approach to prophylaxis and treatment because these regent have uniformity, can be produced in unlimited quantity, can identify important parasite antigens and, therefore, may open up alternative treatment strategies, and can be exhaustively tested using appropriate animal model systems. Since it is likely that these Mabs will be most effective if a maximum number of life cycle stages can be neutralized, we will focus on producing neutralizing MAbs against the sporozoite merozoite and sexual stages of an Ioqa isolate of Cryptosporidium to be provided to all program projects and core facilities. the activity of these MAbs will be tested, either alone or in combination, using immunocompetent neonatal mouse models of neutralization or prophylaxis. In addition, we will test the activity of these MAbs by using an immunocompetent neonatal mouse model of treatment immunocompromised mouse models of prophylaxis and treatment, and by using improved upon or newly developed in vitro cultures to study stage-specific neutralization. Each program project will characterize and isolate relevant stage-specific antigens and will make them available for production of bovine-murine and human MAbs as an alternative treatment strategy for controlling this infection in AIDS patients. Because some of these antigens may be difficult to identify or produce, we will rely on the construction of a cDNA and genomic library and use of appropriate library expression vectors. Monoclonal antibodies showing prophylactic and treatment efficacy and which warrant clinical testing eventually will be produced in quantity.