Animal and Laboratory Core

动物和实验室核心

• 批准号: 8492624
• 负责人: TODD M ALLEN
• 金额: $ 79.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-07 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492624
• 关键词: Address; Adjuvant; Adopted; Animal Model; Animals; Antigens; Autologous; B-Lymphocytes; Biological Models; Blood; Blood specimen; Bone Marrow; CD34 gene; Cell physiology; Cells; Control Groups; Dose; Education; Emergency Situation; Ensure; Event; Exposure to; Fibrous capsule of kidney; Generations; HIV; HIV Infections; Harvest; Hematopoietic; Hematopoietic stem cells; Heterosexuals; Human; Human Resources; Immune; Immune response; Immunodeficient Mouse; Implant; Infection; Instruction; Intervention; Intravenous; Investigation; Laboratory Animals; Liver; Mature T-Lymphocyte; Measures; Methods; Modeling; Monitor; Mus; Names; Operative Surgical Procedures; Osteomyelitis; Plasma; Positioning Attribute; Procedures; Protocols documentation; Research Personnel; Risk; Safety; Sampling; Scientist; Stem cells; T-Lymphocyte; Thymic Tissue; Thymus Gland; Tissue Sample; Tissues; Transplantation; Vaccinated; Vaccination; Vaccines; Vagina; Viral; Viral Load result; Virus; Work; bone; design; experience; fetal; implantation; improved; in vivo; mouse model; nanoparticle; novel; prevent; programs; reconstitution; research study; transmission process; vaginal transmission; vector

Core B, the Animal and Laboratory Core, will provide both the humanized mice, and the HIV viral stocks to infect them with, for all experiments proposed in this application. Core B will generate BLT (bone marrowliver- thymus) humanized mice, which provide one of the recently improved humanized mouse models of HIV infection. BLT mice can be infected with HIV by vaginal transmission, and are capable of producing functional anti-HIV human immune responses. BLT mice are generated by the surgical implantation of human fetal thymic and liver tissue under the renal capsules of immunodeficient mice, concurrently with the intravenous transfer of autologous human hematopoietic stem cells. This protocol allows the human T cells that mature in these mice to be educated by autologous human thymic tissue rather than by the xenogenic mouse thymus. This autologous thymic education appears to result in the much improved T cell function, and consequently much improved human B cell function, that we and others have observed in BLT mice. Core B has already well-established capacity to provide Program investigators with the numbers of wellreconstituted BLT mice that they propose to study in this HIVRAD application. Core B will also perform the vaccinations and/or infections of BLT mice with HIV, and the subsequent harvesting of blood and tissues from these vaccinated and/or HIV-infected mice. Core B personnel have extensive experience in performing HIV studies in BLT mice with collaborating investigators. A strong safety plan is in place to minimize the risk of exposure to Core B personnel performing HIV infections and analyses of HIV-infected BLT mice, and emergency procedures are in place in case any exposure does occur. Core B will also work to improve the BLT model of HIV infection, by developing a low-dose repeated mucosal challenge model. Repetitive challenges will enable the mice to be infected with HIV doses that better represent those encountered in human heterosexual exposure. Core B will also provide virological support to all Program investigators. Core B will generate and titer the stocks of HIV used to infect BLT mice, and measure plasma viral loads in HIV-infected mice by qRT-PCR, using well-established Core B protocols. Core B has in place the demonstrated capacity to provide the multiple Clade B, A and C HIV strains that the experiments of this HIVRAD application will require. Core B thus is well-positioned to support all of the animal and virological requirements of the investigations proposed in this HIVRAD program.

核心B，动物和实验室核心将提供人源化的小鼠和HIV病毒库存 为了感染它们，用于本应用程序中提出的所有实验。核B将产生BLT（骨髓 - 胸腺人性化小鼠，它提供了最近改善的HIV人源化小鼠模型之一 感染。 BLT小鼠可以通过阴道传播感染HIV，并能够产生 功能性抗HIV人类免疫反应。 BLT小鼠是通过手术植入产生的 免疫缺陷小鼠肾囊下的人类胎儿胸腺和肝组织，同时与 自体造血干细胞的静脉转移。该协议允许人类T细胞 这些小鼠中的成熟是由自体胸腺组织教育的，而不是通过异种教育 小鼠胸腺。这种自体性胸腺教育似乎导致了T细胞功能的改善， 因此，我们和其他人在BLT小鼠中观察到了大大改善的人类B细胞功能。 核心B已经建立了良好的能力，可以为计划调查员提供良好的稳定数量 他们建议在此Hivrad应用中研究的BLT小鼠。 核心B还将对HIV进行BLT小鼠的疫苗接种和/或感染，随后 从这些接种和/或HIV感染的小鼠中收集血液和组织。核心B人员有 与合作研究人员在BLT小鼠中进行HIV研究的丰富经验。强大的安全 计划将暴露于核心B人员进行艾滋病毒感染和分析的核心B人员的风险最小 如果确实发生任何暴露，则为感染HIV的BLT小鼠和紧急程序。核心b 还将通过开发低剂量重复粘膜来改善HIV感染的BLT模型 挑战模型。重复的挑战将使小鼠能够感染艾滋病毒剂量更好 代表在人类异性恋中遇到的那些。 核心B还将为所有计划调查人员提供病毒学支持。核心B将产生和滴答 HIV的库存用于感染BLT小鼠，并通过QRT-PCR测量HIV感染小鼠的血浆病毒载量， 使用良好的核心B协议。核心B具有提供的能力来提供 该HIVRAD应用的实验需要多个进化枝B，A和C HIV菌株。 因此，核心B具有很好的位置，以支持所有动物和病毒学要求 在此Hivrad计划中提出的调查。