Aerosol Biology Small Animal Models

气溶胶生物学小动物模型

• 批准号: 8234939
• 负责人: Robert MARK Buller
• 金额: $ 37.91万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234939
• 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; Mouse Pox 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

在第一个获奖期内，MRCE气溶胶生物学/小动物模型核心D(核心D)得到支持 天花疾病研究(使用皮疹病毒、猴痘病毒和牛痘病毒)，因为这种疾病是 在区域7进行了最密集的建模。获得了改良的安卡拉牛痘(MVA)和 ACAM2000(源自Dryvax)的可用性，以及正痘病毒抗病毒药物的I期临床试验， ST-246和CMX001，对额外的正痘病毒治疗药物的体内测试的需求正在减少 还有避孕药。然而，关于先天免疫反应，仍有许多需要了解。 正痘病毒和其他感染性病原体。Core D创建其他模型以用于 基础研究和预防和治疗效果测试被低估了，因为 以下五种致死攻击模型：C57BL/6-sfah“A小鼠体内的甲型流感病毒，日本小鼠体内的猴痘病毒(MPXV) C57BL/6-sfaf1“A小鼠和睡鼠，SARS冠状病毒免疫抑制仓鼠，炭疽杆菌A/J 老鼠。重要的是，实施了更详细的疾病特征的附加化验。 进展(遥测温度和血液丙氨酸氨基转移酶(ALT)和病毒基因组水平 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 特异性的CD4*和CD8+T细胞)。尽管核心D能够通过各种途径感染动物 接种途径，它为呼吸道感染途径的使用提供了特殊的支持。《核心》 也有能力将治疗药物雾化并输送到呼吸道，以研究早期 干预策略。核心学院是美国为数不多的有能力 按照GLP标准测试治疗药物和预防药物。其他核心D服务包括： 动物获取、协议制定、机构动物保护和使用委员会(IACUC)协议 审查，机构生物安全委员会(IBC)协议审查，健康监测，畜牧业，标本 收集、外科服务、临床实验室样本分析、组织学服务和报告撰写。 具体目标1.为区域卓越中心小动物呼吸系统研究人员开发 A-C类优先病原体和新发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，为调查人员提供指定的 被各种病原体感染的小动物的标本、组织和/或细胞 具体目标3：支持A-C类优先事项的治疗和预防药物的临床前试验 病原体和新发传染病病原体