SAFETY AND EFFICACY OF SHIV VACCINE IN MACAQUES

SHIV 疫苗在猕猴中的安全性和有效性

• 批准号: 7349277
• 负责人: OPENDRA NARAYAN
• 金额: $ 5.97万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349277
• 关键词: brain; immunity; infection; live vaccine; macrophage; virus replication

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Two types of studies were supported in this grant. First, studies were directed to mechanisms regulating neuropathogenesis of SHIVKU infection in macaques. This is an X4 virus that invades the brain during the viremic phase of infection and remains dormant until the animal becomes immunosuppressed as a result of the highly productive replication of the virus in CD4 T lymphocytes. Productive virus replication in the brain was confined to macrophages and neuropathological changes correlated with expression of the chemokine CXCL10 that was toxic to neurons and IL-4 that promoted virus replication in the macrophages. Second, continuation of studies on efficacy of a live vaccine showed that immunity induced by the live vaccine depended on persistence of the vaccine virus, and that following elimination of the virus, the animal became susceptible to fatal disease by pathogenic challenge viruses. The live virus apparently failed to induce memory immune responses. The duration of protection by the live vaccine could be extended by re-immunization with the live vaccine. This re-established the persistent infection and the concomitant protective immunity. The persistent infection was characterized by dormant infection and virus replication could only be reactivated by immunosuppression of the immunized animals with antibodies against CD8 lymphocytes. Following recovery of the CD8 cell count, replication of the vaccine virus was again suppressed

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该补助金支持两类研究。首先，研究针对调节猕猴SHIVKU感染的神经发病机制。这是一种X4病毒，在感染的病毒血症阶段侵入大脑，并保持休眠状态，直到动物由于病毒在CD 4 T淋巴细胞中的高效复制而变得免疫抑制。在大脑中的生产性病毒复制仅限于巨噬细胞和神经病理学变化与趋化因子CXCL 10的表达，这是有毒的神经元和IL-4，促进病毒在巨噬细胞中复制。 第二，对活疫苗有效性的继续研究表明，活疫苗诱导的免疫力取决于疫苗病毒的持久性，在病毒消除后，动物变得易受致病性攻毒病毒引起的致命疾病的影响。活病毒显然不能诱导记忆免疫反应。活疫苗的保护期可以通过活疫苗的再免疫来延长。这重新建立了持续性感染和伴随的保护性免疫。持续感染的特点是潜伏感染和病毒复制只能重新激活免疫动物与抗CD 8淋巴细胞的抗体的免疫抑制。CD 8细胞计数恢复后，疫苗病毒的复制再次受到抑制