Aerosol Biology Small Animal Models

气溶胶生物学小动物模型

基本信息

批准号：
7672145
负责人：
Robert MARK Buller
金额：
$ 34.99万
依托单位：
WASHINGTON UNIVERSITY
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：
2009-04-09 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7672145
关键词：
A Mouse A/J Mouse Aerosols Alanine Transaminase Animal Model Animals Antigens Antiviral Agents Award Bacillus anthracis Basic Science Biological Assay Biology Biotechnology Blood CD8B1 gene Categories Cells Clinical Country Development Disease Disease Progression Early treatment Ectromelia Emerging Communicable Diseases Genome Hamsters Health Histology IACUC Immune response Infection Infectious Agent Intervention Laboratories Learning Licensure Modeling Modified Vaccinia Virus Ankara Monkeypox Monkeypox virus Mus Myoxidae Natural Killer Cells Orthopoxvirus Phase I Clinical Trials Preclinical Testing Protocols documentation Public Health Qualifying Reporting Research Research Personnel Respiratory System Respiratory tract structure Route SARS coronavirus Sampling Services Smallpox Specimen T-Lymphocyte Telemetry Temperature Testing Therapeutic Tissues Treatment Efficacy Vaccinia virus Viral Virus Work Writing aerosolized biodefense cytokine efficacy testing granulocyte immunosuppressed in vivo influenzavirus institutional biosafety committee monocyte pathogen prophylactic protocol development respiratory sample collection surgical service weapons

项目摘要

During the first award period the MRCE Aerosol Biology/Small Animal Models Core D (Core D) supported smallpox disease research (using ectromelia, monkeypox, and vaccinia viruses) as this disease was one of the most intensely modeled in Region 7. With licensure of Modified Vaccinia Ankara (MVA) and the availability of ACAM 2000¿ (derived from Dryvax¿), and phase I clinical trials of orthopoxvirus antivirals, ST-246 and CMX001, there is a diminishing need for in vivo testing of additional orthopoxvirus therapeutics and prophylactics. There is, however, still much to learn concerning the innate immune response to orthopxviruses and other infectious agents. The capacity of Core D to create additional models for use in basic research and prophylactic and therapeutic efficacy testing was under-scored by the development of the following five lethal challenge models: influenza virus A in C57BL/6-sfaH"A mice, monkeypox virus (MPXV) in C57BL/6-sfaf1"A mice and dormice, SARS-CoV in immunosuppressed hamsters, and B. anthracis in the A/J mice. Importantly, additional assays were implemented that characterized in greater detail disease progression (temperature by telemetry and blood levels of alanine aminotransferase (ALT) and virus genome equivalents) and the host response to infection (cytokines, NK cells, granulocytes, monocytes, and antigen specific CD4* and CD8+ T cells). Although Core D is capable of infecting animals through a full range of inoculation routes, it provides exceptional support for the use of respiratory routes of infection. The Core also has the capacity to aerosolize and deliver therapeutics to the respiratory tract for the study of early intervention strategies. The Core is one of the few academic facilities in the country to have the capacity to test therapeutics and prophylactics in compliance with GLP standards. Additional Core D services include: animal acquisition, protocol development, Institutional Animal Care and Use Committee (IACUC) protocol review, Institutional Biosafety committee (IBC) protocol review, health surveillance, husbandry, specimen collection, surgical services, clinical laboratory sample analysis, histology services, and report writing. Specific Aim 1. Develop for investigators in the Regional Centers of Excellence small animal respiratory challenge models for Category A-C Priority pathogens and emerging infectious disease agents Specific Aim 2: Carry out respiratory small animal challenges and provide investigators with designated specimens, tissues and/or cells from small animals infected with various agents Specific Aim 3: Support preclinical testing of therapeutics and prophylactics for Category A-C Priority pathogens and emerging infectious disease agents

在第一个奖励期内，MRCE 气溶胶生物学/小动物模型核心 D (Core D) 支持天花疾病研究（使用天花病毒、猴痘病毒和牛痘病毒），因为这种疾病是其中之一 7 区建模最密集。拥有 Modified Vaccinia Ankara (MVA) 和 ACAM 2000 的可用性¿ （源自 Dryvax¿），以及正痘病毒抗病毒药物的 I 期临床试验， ST-246 和 CMX001，对其他正痘病毒疗法的体内测试的需求日益减少然而，关于先天免疫反应，还有很多东西需要了解。 Core D 创建其他模型以供使用的能力。基础研究以及预防和治疗功效测试的发展受到了重视以下五种致死攻击模型：C57BL/6-sfaH"A 小鼠中的甲型流感病毒、猴痘病毒（MPXV） C57BL/6-sfaf1"A 小鼠和睡鼠、免疫抑制仓鼠中的 SARS-CoV 以及 A/J 中的炭疽芽孢杆菌重要的是，进行了额外的测定，以更详细地表征疾病。（遥测温度、丙氨酸转氨酶 (ALT) 和病毒基因组的血液水平等价物）和宿主对感染的反应（细胞因子、NK 细胞、粒细胞、单核细胞和抗原）虽然 Core D 能够通过全方位的方式感染动物。接种途径，它为利用呼吸道感染途径提供了特殊的支持。还具有雾化并向呼吸道输送治疗药物的能力，用于早期研究该核心是该国少数有能力实施干预策略的学术机构之一。符合 GLP 标准的其他核心 D 服务包括：动物采集、方案制定、机构动物护理和使用委员会 (IACUC) 方案审查、机构生物安全委员会 (IBC) 方案审查、健康监测、饲养、标本采集、手术服务、临床实验室样本分析、组织学服务和报告撰写。具体目标 1. 为区域卓越中心的研究人员开发小动物呼吸道 A-C 类优先病原体和新出现的传染病病原体的挑战模型具体目标 2：开展呼吸道小动物挑战并为研究人员提供指定的来自感染各种病原体的小动物的标本、组织和/或细胞具体目标 3：支持 A-C 类优先级治疗剂和预防剂的临床前测试病原体和新出现的传染病病原体