Antibody-Biocide Fusions to Control Cryptosporidium

描述（由申请人提供）：本研究的目标是开发用于微小隐孢子虫的治疗产品，其可以以可行的规模和成本生产，用于向大量患者或处于风险中的个人提供治疗产品，这可能是打击生物恐怖主义或保护实地部署的武装部队所必需的。 我们的方法是开发重组中和性单克隆抗体，以及将单克隆抗体与中和C.小孢子和裂殖子。我们将使用专有的逆转录载体基因转移技术将单克隆融合产物候选物的多顺反子基因构建体插入细胞培养物中。在确定产品在体外和小鼠模型中有效后，我们将扩大细胞培养中的生产，并通过创建在其乳汁中表达单克隆抗体和融合蛋白的转基因牛，并在新生小鼠和猪模型中测试抗隐孢子虫的功效。转基因表达将使得能够经济地和大规模地制造抗隐孢子虫治疗剂。除了生物防御应用外，所开发的技术还将在治疗机会性C感染方面具有重要的双重用途。小孢子虫和旅行者腹泻，并在兽医中用于减少感染的环境水库。

DESCRIPTION (provided by applicant): The goal of this research is develop therapeutic products for Cryptosporidium parvum which can be made at a scale and cost which are feasible for delivery to large populations of patients or individuals at risk, as may be necessary in countering bioterrorism, or in protecting field-deployed armed forces. Our approach is to develop recombinant neutralizing monoclonal antibodies, and fusion proteins that genetically link monoclonal antibodies to parasiticidal proteins (biocides) which neutralize C. parvum sporozoites and merozoites. We will use a proprietary retrovector gene transfer technology to insert multicistronic gene constructs for the monoclonal fusion product candidates into cell culture. Following identification of products effective in vitro and in mouse models, we will scale up production in cell culture and by creation of transgenic cattle that express the monoclonal antibodies and fusion proteins in their milk and test anti-cryptosporidial efficacy in neonatal mice and pig models. Transgenic expression will enable manufacture of anti-cryptosporidial therapeutics economically and on a large scale. In addition to biodefense applications, the technology developed will also have important dual-use application in treatment of opportunistic infections with C. parvum and traveler's diarrhea, and in veterinary use to reduce the environmental reservoir of infection.