IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

微小隐孢子虫可引起艾滋病患者持续性腹泻 病人。感染艾滋病患者的数量很可能是 被低估了。不幸的是，化疗的尝试已经 到目前为止，这一切都失败了。最近的研究提供了证据表明，治疗与 高免抗体制剂可显著降低急性胰腺炎的严重程度 疾病。根据这一想法，我们计划将重点放在克隆 抗体(Mab)预防和治疗的途径，因为这些试剂 具有一致性，可不限量生产，可识别 重要的寄生虫抗原，因此可能会开辟替代 治疗策略，并且可以使用适当的 动物模型系统。 因为这些单抗可能是最有效的，如果最大 生命周期阶段的数量可以中和，我们将专注于生产 抗子孢子、裂殖子和性阶段的中和单抗 将向所有计划项目提供隐孢子虫Ioqa分离株 核心设施。这些单抗的活性将被测试，或者单独测试 或组合使用具有免疫活性的新生小鼠模型 中和或预防。此外，我们还将测试 这些单抗通过使用具有免疫活性的新生小鼠模型进行治疗 免疫低下小鼠的预防和治疗模型，并通过使用 改进或新开发的体外培养以研究特定阶段 中和。每个计划项目都将描述和隔离 相关的阶段特异性抗原，并将使它们可用于 制备牛-鼠和人的单抗作为替代治疗 控制艾滋病患者感染的策略。因为有些人 这些抗原可能很难识别或生产，我们将依靠 CDNA和基因组文库的构建及相应文库的使用 表达载体。显示预防性和可塑性的单抗 治疗的有效性和最终值得临床测试的将是 大量生产的。

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.