IMPROVEMENT OF THE COTTON RAT MODEL OF HUMAN DISEASES

1995年，食品和药物管理局批准了RespiGam TM，一种血浆- 衍生的多克隆IgG制剂，用于预防严重 呼吸道合胞病毒（RSV）肺炎。 一九九七年十二月， 生物制品许可证申请已提交给FDA进行第二次- 第二代RSV预防剂，Synagis TM，第一个单克隆抗体 在临床试验中显示对感染性疾病有疗效 剂 这两个事件强调了自交系棉花的重要性 大鼠（Sigmodon物种）的生物医学研究，因为所有的 支持这两种药物的临床前数据是在棉鼠中产生的。 RSV感染模型。 然而，还有其他紧迫的生物医学问题， 问题，涉及候选RSV疫苗安全性; HIV、流感、疱疹 单纯、麻疹和副流感病毒;外来和新出现的病毒; 以及使用腺病毒载体的遗传和癌症治疗， 棉鼠似乎是一种优选的模型。 这些问题 不能充分解决，因为基础的复杂性 生物学需要特异性的免疫和遗传试剂， 棉花鼠，目前还没有。 我们已经开始了一个 程序，使用免疫学和分子生物学的方法， 产生的试剂，这将允许国家的最先进的研究， 模型 本申请的拟议工作范围是开发一个 针对棉鼠细胞表面抗原的试剂库， 细胞因子和趋化因子。

In 1995 the Food and Drug Administration licensed RespiGam TM, a plasma- derived polyclonal IgG formulation, for the prevention of severe respiratory syncytial virus (RSV) pneumonia. In December, 1997, a Biologic License Application was submitted to the FDA for a second- generation RSV preventive, Synagis TM, the first monoclonal antibody ever shown in clinical trials to have efficacy against an infectious agent. These two events underscore the importance of the inbred cotton rat (Sigmodon species) in biomedical research, since all of the preclinical data supporting both drugs were generated in the cotton rat model of RSV infection. However, there are other pressing biomedical issues, involving candidate RSV vaccine safety; HIV, influenza, herpes simplex, measles and parainfluenza viruses; exotic and emerging viruses; and genetic and cancer therapy using adenovirus vectors, for all of which the cotton rat appears to be a preferred model. These issues cannot be addressed adequately because the complexity of the underlying biology requires immunologic and genetic reagents specific for the cotton rat, which are not yet available. We have already begun a program, using methodologies of immunology and molecular biology, to generate the reagents which will allow state-of-the-art studies in this model. The proposed workscope of this application is to develop a library of reagents directed against cotton rat cell-surface antigens, cytokines and chemokines.