Human Abs to B. Anthracis in Cloned Transgenic Cattle

克隆转基因牛对炭疽杆菌的人抗体

• 批准号: 6583447
• 负责人: Thillainayagam Sathiyaseelan
• 金额: $ 13.73万
• 依托单位: HEMATECH, LLC
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2003-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6583447
• 关键词: Bacillus anthracis; anthrax; antibacterial antibody; biotechnology; bioterrorism /chemical warfare; cow; enzyme linked immunosorbent assay; genetically modified animals; immunoglobulin genes; immunologic substance development /preparation; intravenous administration; neutralizing antibody

DESCRIPTION (provided by the applicant): Anthrax is considered a possible bioterrorist threat because of its lethality and its durability. Several nations have had bioweapons programs in the past that produced large quantities of anthrax. Numerous anthrax scares and the recent deaths from exposure to anthrax spores sent through the mail have heightened concerns about protecting the population against anthrax. No mass vaccination program is envisioned because the existing anthrax vaccine is in short supply. In the absence of a vaccine, passive immunization with intravenous immunoglobulin (IVIG) of people exposed to anthrax spores is a reasonable strategy. This proposal is to develop a large animal system for producing human polyclonal antibody against anthrax. It has been shown that transgenic mice carrying an artificial human chromosome (HAC) produce human antibody of all classes and with a broad repertoire when challenged with antigen. In the current work, a similar strategy would be applied to cattle, where the yield of antibody would be far greater than with mice. We have already shown that we can create cattle clones that have a HAC containing the human IG genes, and that the chromosome is stable and is expressed throughout fetal development into neonatal life. Work is proposed to characterize the immune response to anthrax vaccine and purified anthrax proteins in normal and in cloned calves. This novel and practical solution to the limited supply of human IVIG has several advantages. First, it would enable the production of large quanitites of human antibody at a reasonable cost. Second, it would provide greater flexibility in designing immunization strategies for producing high, titer, high specificity antibody beyond what is possible with human volunteers. Third, it would provide a new enabling technology for producing clinically important human antibody reagents against other bacterial and viral pathogens.

描述（由申请方提供）：炭疽因其致命性和持久性而被认为是一种可能的生物恐怖威胁。 一些国家过去曾有过生产大量炭疽的生物武器计划。 无数的炭疽恐慌和最近因接触通过邮件发送的炭疽孢子而死亡的事件加剧了人们对保护人口免受炭疽感染的担忧。 由于现有的炭疽疫苗供应短缺，没有设想大规模接种疫苗计划。 在没有疫苗的情况下，对接触炭疽孢子的人进行静脉注射免疫球蛋白（IVIG）的被动免疫是一种合理的策略。 本研究旨在建立一个大规模的动物系统，用于生产抗炭疽的人源性多克隆抗体。 已经表明，携带人工人染色体（HAC）的转基因小鼠在用抗原攻击时产生所有类别的人抗体并且具有广泛的库。 在目前的工作中，类似的策略将应用于牛，其中抗体的产量将远远高于小鼠。 我们已经证明，我们可以创建具有包含人类IG基因的HAC的牛克隆，并且染色体是稳定的，并且在整个胎儿发育到新生儿生命中表达。 工作的特点，炭疽疫苗和纯化的炭疽蛋白在正常和克隆小牛的免疫反应。 这种新颖而实用的解决人类IVIG有限供应的方案具有几个优点。 首先，它将能够以合理的成本生产大量的人抗体。 其次，它将在设计免疫策略方面提供更大的灵活性，以产生超出人类志愿者可能的高滴度、高特异性抗体。 第三，它将提供一种新的使能技术，用于生产临床上重要的针对其他细菌和病毒病原体的人类抗体试剂。