IMMUNOTHERAPY OF CRYPTOSPORIDIOSIS USING MONOCLONALS

微小隐孢子虫是持续性腹泻病的主要原因。 在艾滋病患者中。目前的估计是，15%-20%的艾滋病人 患者最终可能会感染这种感染。这类人的真实数量 然而，患者目前尚不清楚，而且很可能被低估。 艾滋病患者中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，口服高免疫抗体制剂 可能会降低疾病的严重程度。贯彻这一理念，我们 专注于用单抗(MAb)来预防和 处理因为这些试剂具有一致性，可以在 不限数量，可以识别重要的寄生虫抗原，可以 使用体外和体内模型系统进行了详尽的测试，并可能 有助于开辟替代的预防或治疗策略。 在这份持续计划项目建议书中，我们将重点介绍 制定免疫战略的综合方法，旨在 防治艾滋病患者的隐孢子虫病。堆芯 将建立设施，向所有人提供寄生虫试剂 项目(9001亚利桑那州)，以提供一种测试有用的单抗的手段 抗肠道和肠外隐孢子虫病，并鉴定 利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2将广泛互动 并专注于与识别和表征中和有关的工作 单抗分别针对裂殖子和子孢子期。 华盛顿的项目3将专注于重组战略，旨在 生产和鉴定子孢子和裂殖子蛋白 诱导对微小隐孢子虫的保护性反应。亚利桑那州的项目4将 抗子孢子抗原小鼠二聚体IgA单抗的研制 已知对中和敏感，并可用于策略 控制肠外隐孢子虫病。整个项目将 由亚利桑那州执导。

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.