Hamster Models and Reagents for Biodefense Research

用于生物防御研究的仓鼠模型和试剂

基本信息

批准号：
6773848
负责人：
LYNN SOONG
金额：
$ 28.01万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-15 至 2006-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The Syrian golden hamster is highly susceptible to a variety of intracellular pathogens, and serves as an excellent model for these pathogens' corresponding human diseases. At present, the hamster is the only practical animal model for human viral hemorrhagic fever syndrome caused by arenaviruses and phlebovirus, and for human hantavirus pulmonary syndrome. Most of these viruses are highly infectious by aerosol, causing rapidly progressing symptoms with an extremely high case fatality. The potential use of these viruses as biological warfare agents is an increasing concern. Despite their severity and obvious public health importance, there is a paucity of information on the pathogenesis of these high-containment pathogens. This is in part due to the lack of adequate small animal models. Commonly used laboratory strains of mice can be persistently infected, without overt clinical and pathological changes. Recent studies have indicated that infected hamsters can closely resemble certain features of human diseases; however, their utility in disease research has been hampered because there are currently almost no hamster immunological reagents available commercially. In this application, we will take a genetic immunization approach to generate high titer rabbit antibodies specific to hamster cytokines and cell surface molecules that are known to play critical roles in innate and cell-mediated immunity. We will then apply these antibodies in hamster models of hantavirus pulmonary syndrome and yellow fever virus infection, aimed at examining whether host immune responses contribute to disease pathogenesis. This proposal represents a distinct area of investigation and should open numerous avenues for the use of hamsters in the study of pathogens that represent important bioterrorism and emerging disease threats.

描述（由申请人提供）：叙利亚黄金仓鼠非常容易受到各种细胞内病原体的影响，并且是这些病原体相应的人类疾病的出色模型。目前，仓鼠是由体育症病毒和鼻虫病毒以及人汉塔病毒肺综合症引起的人类病毒出血综合征的唯一实用动物模型。这些病毒中的大多数受气溶胶具有高度感染力，导致病例极高的症状迅速发展。这些病毒作为生物战剂的潜在用途是越来越多的关注点。尽管它们的严重程度和明显的公共健康重要性，但关于这些高传输病原体的发病机理的信息很少。这部分是由于缺乏足够的小动物模型。通常可以持续感染小鼠的常用实验室菌株，而无需明显的临床和病理变化。最近的研究表明，受感染的仓鼠可能与人类疾病的某些特征非常相似。但是，它们在疾病研究中的效用受到了阻碍，因为目前几乎没有商业上可用的仓鼠免疫学试剂。在此应用中，我们将采用一种遗传免疫方法来产生针对仓鼠细胞因子和细胞表面分子的高滴水兔抗体，这些抗体已知在先天和细胞介导的免疫中起关键作用。然后，我们将在汉塔病毒肺综合征和黄热病病毒感染的仓鼠模型中应用这些抗体，旨在检查宿主免疫反应是否有助于疾病发病机理。该提案代表了一个独特的调查领域，应该为在代表重要的生物恐怖主义和新兴疾病威胁的病原体研究中开辟许多途径。