Aerosol Biology Small Animal Models

气溶胶生物学小动物模型

• 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
• 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

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

在第一个奖项期间 天花疾病研究（使用伊特罗梅利亚，蒙基托和牛ac病毒），因为这种疾病是一种 在第7区建模的最强烈的模型，并获得了修改后的Ankara（MVA）的许可证和 ACAM2000®的可用性（源自Dryvax€）和正前氧化病毒抗病毒药的I期临床试验， ST-246和CMX001，对其他正托病毒疗法的体内测试的需求减少 和预防学。但是，关于先天免疫的反应仍然有很多要学习的 正交病毒和其他传染剂。核心D创建其他模型的能力 基础研究以及预防性和治疗效率测试的得分不足 以下是五个致命的挑战模型：C57BL/6-SfaH中的影响力A，“小鼠，Monkeypox病毒（MPXV） C57BL/6-SFAF1“ A/J/j中的ham鼠，免疫抑制的仓鼠中的SARS-COV，A/J 老鼠。重要的是，实施了更多详细疾病特征的其他测定 进展（通过遥测和血液水平的温度丙氨酸氨基转移酶（ALT）和病毒基因组 等效物）和对感染的宿主反应（细胞因子，NK细胞，粒细胞，单核细胞和抗原 特定的CD4*和CD8+ T细胞）。尽管核心D能够通过全部范围感染动物 接种途径，它为使用呼吸道感染途径提供了出色的支持。核心 还具有为呼吸道增生和提供治疗的能力，以进行早期研究 干预策略。核心是该国为数不多的学术机构之一 测试疗法和预防药物符合GLP标准。其他核心D服务包括： 动物获取，协议开发，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）协议审查，健康监视，饲养，标本 收集，外科服务，临床实验室样本分析，组织学服务和报告写作。 特定目的1。为卓越地区小动物呼吸道中心的调查员开发 A-C类优先病原体和新兴传染病药物的挑战模型 特定目的2：进行呼吸小动物挑战，并为调查人员提供指定的 感染各种药物的小动物的标本，组织和/或细胞 特定目的3：支持A-C类优先级治疗和预防药物的临床前测试 病原体和新兴的传染病药物