Non-Human Primate and Imaging Core

非人类灵长类动物和成像核心

基本信息

批准号：
10224631
负责人：
Francois J Villinger
金额：
$ 46.14万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-05 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224631
关键词：
Address Adult Anti-Retroviral Agents Antiviral Agents Antiviral Response Bar Codes Biopsy Blood Cell Lineage Cells Clinical Collection Combined Modality Therapy Data Exposure to Female Formulation Goals HIV HIV Infections HIV-1 Hour Image Imaging Techniques Imaging technology Immune Immune response ImmunoPET Immunotherapeutic agent Immunotherapy Infection Interruption Intervention Laboratories Lymphoid Lymphoid Tissue Macaca mulatta Maintenance Maps Modeling Monitor Mucous Membrane Organ Pathogenesis Pathway interactions Patients Penetration Pharmaceutical Preparations Plasma Primates Probability Prophylactic treatment Reporter Residual state SIV Series Shock Site Time Tissues Vagina Viral Viral Load result Viral reservoir Viremia Virus Virus Latency Virus Replication acute infection base fluorophore immunological intervention in vivo mTOR inhibition neutralizing antibody nonhuman primate novel prevent programs rectal therapy design treatment duration vaginal infection viral rebound

项目摘要

Summary - Core B: Non-human Primate and Imaging Core A major barrier to HIV cure is the persistence of HIV-1 infected cells that constitute the viral reservoir. While current antiretroviral combination therapies are able to inhibit viral replication to below detectable levels (50 copies) in the plasma of patient, ART cessation almost invariably leads to viral resurgence even in patients for which ART was initiated early post infection. This has led to the formulation of Shock and Kill approaches to activate and reduce the reservoirs using latency reversing agents under the umbrella of ART, though such approach in the absence of immunotherapy has not had any clinical benefit thus far. However, these results clearly indicate that long-term persistent HIV reservoirs are seeded rapidly post infection as confirmed it the nonhuman primate model of HIV. In addition, data from several groups and ours strongly suggest that residual viral replication is actually ongoing in various lymphoid tissues in spite of highly active ART, be it due to poor drug penetration, conversion or sanctuaries with limited antiviral immune contribution. In this application, we propose to quantify and map the early reservoir formation after vaginal infection and early ART intervention, using a series of state of the art imaging techniques as well detailed cellular analyses of the reservoirs obtained at various times of ART initiation. Next we propose to address the functional reservoir following prolonged ART and ART interruption, monitoring residual viral replication in tissues, sites of early viral rebound, the cellular origin of the active reservoir and immune interventions designed to bolster antiviral responses leading to antiviral control.

摘要 - 核心B：非人类灵长类动物和成像核心 HIV治疗的主要障碍是构成病毒储量的HIV-1感染细胞的持久性。尽管当前的抗逆转录病毒组合疗法能够抑制病毒复制至低于可检测水平（50个副本）在患者的血浆中，ART戒烟几乎总是导致病毒复活在感染后早期开始了哪种艺术。这导致了震惊和杀戮方法的制定使用延迟逆转剂在艺术保护下激活和减少储层，尽管到目前为止，在没有免疫疗法的情况下，方法没有任何临床益处。但是，这些结果清楚地表明，长期持续的艾滋病毒库是在感染后迅速播种的，如它证实艾滋病毒的非人类灵长类动物模型。此外，来自几个小组的数据强烈表明残留尽管有高度活性，但实际上在各种淋巴组织中仍在进行病毒复制抗病毒免疫贡献有限的药物渗透，转化率或保护区。在此应用程序中，我们建议在阴道感染和早期艺术干预后量化和绘制早期的水库形成，使用一系列最先进的成像技术以及储层的详细蜂窝分析在各个艺术启动时获得。接下来，我们建议解决功能储层以下长时间的艺术和艺术中断，监测组织中的残留病毒复制，早期病毒的部位反弹，活性储层的细胞起源和旨在增强抗病毒的免疫干预措施导致抗病毒控制的反应。