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Antibody-Biocide Fusions to Control Cryptosporidium

抗体-杀菌剂融合来控制隐孢子虫

基本信息

批准号：
8118996
负责人：
MICHAEL IMBODEN
金额：
$ 100万
依托单位：
IOGENETICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-21 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8118996
关键词：
Affect Affinity Chromatography Agriculture Animal Model Animal Testing Animals Antibodies Binding Biocide Biological Response Modifier Therapy Categories Cattle Cell Culture Techniques Characteristics Child Chimeric Proteins Clinical Clinical Trials Cold Chains Country Cryptosporidiosis Cryptosporidium Cryptosporidium parvum Development Disease Disease Outbreaks Drug Formulations Economics Engineering Ensure Enzymes Epitopes Evaluation Family suidae Filtration Genes Gerbils Goals Government Health Human Hybridomas Immunocompetent Immunocompromised Host Immunoglobulin Constant Region In Vitro Individual Infection Investigational Drugs Lead Learning Licensing Livestock Marketing Milk Modeling Molecular Epidemiology Monoclonal Antibodies Mus Neonatal Oocysts Oral Organism Orphan Drugs Pathway interactions Patients Persons Pharmaceutical Preparations Phase Population Positioning Attribute Production Proteins Readiness Recombinant Fusion Proteins Recombinant Proteins Recombinants Reporting Research Sampling Small Business Innovation Research Grant Solutions Source Sporozoites Surface System Testing Therapeutic Time Transgenic Organisms Travel Work Writing antimicrobial peptide biothreat combat cost economic impact efficacy testing in vitro testing in vivo in vivo Model interest man natural antimicrobial neutralizing antibody novel programs stable cell line tissue culture

项目摘要

DESCRIPTION (provided by applicant): Cryptosporidiosis is a leading cause of diarrheal disease worldwide and is a category B biothreat agent. Two major species, Cryptosporidium hominis and Cryptosporidium parvum are responsible for over ninety percent of cases in man. C. parvum is zoonotic, with a reservoir in cattle, where it is an economically important cause of disease. There is currently no specific drug for cryptosporidiosis. The goal of this project is to bring to the point of readiness for out-licensing Directed BiocideTM therapeutics which target Cryptosporidium species affecting man and livestock and which are effective in oral treatment of cryptosporidiosis. The Directed BiocideTM approach creates a recombinant fusion protein in which an antibody targeting a surface epitope on Cryptosporidium sporozoites delivers an anticryptosporidial biocide comprising a natural antimicrobial peptide or enzyme to the surface of the sporozoite. With this approach Directed BiocideTM products are effective at far lower concentrations than a sporozoite-neutralizing antibody acting alone. Additional Directed BiocidesTM will be developed to target all causal species of human cryptosporidiosis, including C. hominis, and will be tested in vitro and in multiple animal models. Purification strategies will be established for these novel fusion protein products which will be suitable for human use products. The project also continues research to produce anticryptosporidial Directed BiocidesTM in milk of transgenic cattle for oral treatment of livestock or large populations. PUBLIC HEALTH RELEVANCE: Cryptosporidiosis is one of the most important causes of diarrheal disease worldwide, affecting both immunocompromised and immunocompetent individuals and sometimes causing mass outbreaks. Cryptosporidium is a Category B biothreat agent. Currently there is no effective drug available for cryptosporidiosis. This project develops a novel recombinant protein drug to neutralize the two species of Cryptosporidium that are responsible for over 90% of cases affecting humans.

描述（由申请人提供）：隐孢子虫病是全球范围内导致疟疾的主要原因，属于B类生物威胁因子。两个主要的物种，人隐孢子虫和微小隐孢子虫是造成人类90%以上病例的原因。细小病毒是人畜共患疾病，在牛中具有宿主，是一种经济上重要的疾病原因。目前还没有针对隐孢子虫病的特效药。该项目的目标是为定向杀生物剂TM治疗剂的外许可做好准备，该治疗剂针对影响人类和牲畜的隐孢子虫物种，并有效地口服治疗隐孢子虫病。定向杀生物剂TM方法产生重组融合蛋白，其中靶向隐孢子虫子孢子上的表面表位的抗体将包含天然抗微生物肽或酶的抗隐孢子虫杀生物剂递送至子孢子表面。通过这种方法，Directed BiocideTM产品在远低于单独作用的子孢子中和抗体的浓度下有效。将开发更多的定向杀生物剂TM，以针对人类隐孢子虫病的所有致病物种，包括C。人，并将在体外和多种动物模型中进行测试。将为这些新的融合蛋白产品建立纯化策略，这些产品将适用于人用产品。该项目还继续研究在转基因牛的牛奶中生产抗隐孢子虫的定向杀生物剂TM，用于牲畜或大规模人口的口服治疗。公共卫生关系：隐孢子虫病是世界范围内最重要的肠道疾病之一，影响免疫功能低下和免疫功能正常的个体，有时会引起大规模爆发。隐孢子虫属B类生物威胁因子。目前尚无有效的药物治疗隐孢子虫病。该项目开发了一种新的重组蛋白药物，以中和两种隐孢子虫，这两种隐孢子虫是90%以上影响人类的病例的原因。