Aerosol Biology Small Animal Models

在第一个奖项期间，MRCE气溶胶生物学/小动物模型核心D（核心D）支持 天花疾病研究（使用鼠痘，猴痘和牛痘病毒），因为这种疾病是 在第七区建模最密集。随着许可证的修改牛痘安卡拉（MVA）和 ACAM 2000的可用性（来自Dryvax），以及正痘病毒抗病毒药物的I期临床试验， ST-246和CMX 001，对另外的正痘病毒治疗剂的体内测试的需要逐渐减少 和物理学。然而，关于先天免疫反应， 正病毒和其他传染性病原体。核心D创建其他模型的能力， 基础研究和预防和治疗效果测试被开发的 以下五种致死性攻击模型：C57 BL/6-sfaH-A小鼠中的流感病毒A，C57 BL/6-sfaH-A小鼠中的猴痘病毒（MPXV）， C57 BL/6-sfaf 1-A小鼠和睡鼠，免疫抑制仓鼠中的SARS-CoV，和B。A/J炭疽病 小鼠重要的是，实施了额外的测定，其更详细地表征了疾病 进展（遥测体温和丙氨酸转氨酶（ALT）和病毒基因组的血液水平 等效物）和宿主对感染的应答（细胞因子、NK细胞、粒细胞、单核细胞和抗原 特异性CD 4 * 和CD 8 + T细胞）。虽然核心D能够通过各种途径感染动物， 在预防接种途径方面，它为使用呼吸道感染途径提供了特别支持。核心 还具有雾化和递送治疗剂到呼吸道的能力，用于研究早期 干预策略。核心是该国为数不多的学术设施之一，有能力， 根据GLP标准测试治疗剂和药物。其他核心D服务包括： 动物获取、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 收集、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系统 A-C类重点病原体和新出现的传染病病原体的挑战模型 具体目标2：开展呼吸系统小动物挑战，并为研究者提供指定的 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类优先级的治疗药物和药理学药物的临床前试验 病原体和新发传染病病原体

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