IMPROVEMENT OF THE COTTON RAT MODEL OF HUMAN DISEASES

1995年，美国食品和药物管理局批准了RespiGam TM，一种血浆- 衍生多克隆免疫球蛋白制剂，用于预防严重的 呼吸道合胞病毒肺炎。1997年12月，一位 生物许可证申请第二次提交给FDA- 第一代RSV预防性，Synagis TM，首个单抗 曾在临床试验中被证明对感染性疾病有效 探员。这两件事凸显了近交棉的重要性。 在生物医学研究中的大鼠(剑齿目)，因为所有的 在棉鼠身上产生了支持这两种药物的临床前数据 呼吸道合胞病毒感染模型。然而，还有其他紧迫的生物医学 问题，涉及候选RSV疫苗的安全性；艾滋病毒、流感、疱疹 单纯、麻疹和副流感病毒；外来病毒和新出现的病毒； 以及使用腺病毒载体的遗传和癌症治疗，用于所有 棉花鼠似乎是首选的模型。这些问题 不能充分解决，因为基础的复杂性 生物学需要免疫和遗传试剂，专门针对 棉鼠，目前还没有。我们已经开始了一场 程序，使用免疫学和分子生物学的方法， 产生试剂，使最先进的研究在这方面 模特。此应用程序的建议工作范围是开发一个 针对棉鼠细胞表面抗原的试剂文库， 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.