Monitoring SIV Reservoirs with Whole Body immunoPET

使用全身免疫 PET 监测 SIV 储库

基本信息

批准号：
9301446
负责人：
PHILIP J SANTANGELO
金额：
$ 159.08万
依托单位：
UNIVERSITY OF LOUISIANA AT LAFAYETTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-15 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301446
关键词：
Acquired Immunodeficiency Syndrome Acute Address Affect Affinity Anatomy Animal Model Anti-Retroviral Agents Antiviral Agents Biomedical Engineering Biopsy Blood CD4 Positive T Lymphocytes Cell Lineage Cells Clinic Clinical Coupled Development Disease Progression Drug Kinetics Exposure to Foundations Goals HIV HIV Infections Human Image Imaging Techniques Immune In Situ In Vitro Individual Infection Infection prevention Interruption Kinetics Label Lymphoid Tissue Macaca Macaca mulatta Maps Measures Metabolism Methods Modeling Monitor Monkeys Monoclonal Antibodies Nature Organ Outcome Pathology Patients Pattern Pharmaceutical Preparations Pharmacodynamics Plasma Positron-Emission Tomography Preventive measure Primates Process Protocols documentation Radionuclide Imaging Regimen Residual state Route SIV Sampling Signal Transduction Site Technetium Tc 99m ciprofloxacin Techniques Testing Therapeutic Time Tissue Banks Universities Vaccines Vagina Variant Viral Viral Load result Viral Proteins Viral reservoir Virus Virus Diseases Virus Replication X-Ray Computed Tomography antiretroviral therapy base body map clinical application design imaging modality immune activation improved in vivo innovation minimally invasive nonhuman primate novel novel strategies public health relevance rectal simian human immunodeficiency virus tool transmission process viral RNA viral detection virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): With the advent of novel anti-retroviral therapies, the prospect of potentially eliminating HIV from infected patients may become an achievable goal. However, such goal will require new tools with greater sensitivity than currently available to monitor the progress of such therapy, no only in blood but also in organs that do harbor such reservoirs and sites of residual viral replication in vivo. In addition, identifying early seeding of viral reservoirs during acute infecton relative to the route of transmission and disease progression may open novel directions for chemotherapeutic or immune barriers to contain the new virus infection foyers and generalized dissemination of the infection with seeding of viral reservoirs. To harness such early viral dynamics and account for the natural individual variation that exists for such dynamics, there is a need to understand the dissemination patterns of HIV infection following mucosal transmission, the primary transmission mode of infection worldwide. However, the tools currently available to monitor such viral processes are either indirect or relatively invasive and clearly impractical for the human clinic. Even when one uses the nonhuman primate model of AIDS, understanding the viral dynamics in real time is challenging and prohibitively expensive if one chooses to perform serial sacrifices, not to mention fraught by a high degree of variability between individuals. In this project, we propose to optimize our established immuno-positron emission tomography (PET) with simultaneous X-ray computed tomography (CT), to determine real-time whole body maps of simian immunodeficiency virus replication sites in vivo to chart out the total body replication sites of SIV in vivo and determine viral dynamics and sites of residual viral replication during antiretroviral therapy. Thus we propose to determine the anatomic SIV viral dynamics following infection via the IV, rectal and vaginal route to determine the consecutive major sites of viral replication in vivo, which will be confirmed via targeted tissue collections. Next we will compare 2 combination ART therapies for reducing viral reservoirs and document residual foyers of replication in vivo as well as determine which such reservoirs might be fueling the viral resurgence after interruption of ART in vivo. We submit that these studies wil provide critical information for the design of HIV eradication strategies in human HIV infection.

描述（由申请人提供）：随着新型抗逆转录病毒疗法的出现，可能会从感染患者中消除HIV的前景可能成为一个可实现的目标。但是，此类目标将需要比目前可用的新工具，以监测这种疗法的进展，不仅在血液中，而且还具有在体内含有此类储层和残留病毒复制位置的器官中。此外，相对于传播和疾病进展途径，在急性感染过程中确定病毒储存剂的早期播种可能会为化学治疗或免疫屏障的新方向开放，以含有新的病毒感染子宫门厅，并通过病毒储层的播种对感染的广义传播。为了利用这种早期的病毒动力，并解释了这种动态的自然个性变化，需要了解粘膜传播后艾滋病毒感染的传播模式，粘膜传播是全球感染的主要感染模式。但是，目前可用于监测此类病毒过程的工具是间接或相对侵入性的，对于人类诊所来说是显而易见的。即使人们使用非人类灵长类动物的艾滋病模型，如果一个人选择执行串行牺牲，实时理解病毒动态也是一项挑战和昂贵的，更不用说因个人之间的高度可变性而造成的。在这个项目中，我们建议通过同时X射线计算机断层扫描（CT）优化我们已建立的免疫斑岩发射断层扫描（PET），以确定在体内实时全身图的实时全身图，以在体内绘制体内复制的总体复制位点，并确定病毒式动态效果。因此，我们建议通过IV，直肠和阴道途径在感染后确定解剖学SIV病毒动力学，以确定体内病毒复制的连续主要部位，这将通过靶向组织收集确认。接下来，我们将比较2种减少病毒储层和记录体内复制的残留门厅的组合艺术疗法，并确定在体内中断艺术后，哪些此类储层可能会助长病毒的复活。我们认为，这些研究将为人类艾滋病毒感染中的艾滋病毒根除策略设计提供关键信息。