TB INFECTION IN NHP MODEL OF PEDIATRIC AIDS

NHP 儿科艾滋病模型中的结核感染

• 批准号: 8357722
• 负责人: Marie-Claire Elisabeth Gauduin
• 金额: $ 18.16万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357722
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Animals; Cause of Death; Characteristics; Child; Clinical; Data; Deterioration; Development; Disease; Disease Progression; Dose; Emergency Situation; Funding; Goals; Grant; HIV; HIV-1; Highly Active Antiretroviral Therapy; Immune response; Immune system; Immunity; Infant; Infection; Intervention; Life; Macaca; Macaca mulatta; Modeling; Monkeys; Mothers; Mycobacterium tuberculosis; National Center for Research Resources; Neonatal; Newborn Infant; Newborn Infant Diseases; Opportunistic Infections; Patients; Pilot Projects; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Source; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Work; cost; efficacy testing; experience; fighting; mortality; nonhuman primate; pathogen; pediatric AIDS; pregnant; response; tuberculosis treatment; vaccine safety

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tuberculosis is the leading cause of death in AIDS patients worldwide, is one of the earliest opportunistic infections occurring in conjunction with HIV, and is an accelerant of the replication of HIV and subsequent deterioration of the immune system. Each year, one million children worldwide become newly infected with tuberculosis (TB) and 420,000 with HIV. Co-infection with Mtb and HIV, the "cursed duet," is an increasing global emergency. Although the use of highly active antiretroviral therapy during TB treatment in HIV-1/Mtb co-infected patients is associated with reduced mortality, it can also be in life threatening. A monkey model of HIV/Mtb co-infection is desperately needed so that cocktail treatments can be developed to fight both pathogens simultaneously. As vaccines for TB and AIDS are developed for adults, the infant monkey model also will become important for testing the efficacy and safety of these vaccines in infants (and in pregnant mothers who may transmit immunity to their infants passively). We have considerable experience with the infant rhesus model for AIDS and we also have considerable experience with the adult rhesus model of TB. We propose to establish and optimize a rhesus macaque newborn/infant model for TB infection to characterize the clinical, bacteriological, and immunological characteristics of disease progression. This work, which will be conducted in our ABSL-3 facility, is expected to provide sufficient data to establish a dose that is high enough to cause gradual development of TB disease, and not so high that the animals succumb too quickly to enable experimental interventions, particularly in co-infected animals. The overall goal is to establish a neonatal nonhuman primate tuberculosis model that mimics clinical, bacteriological, and immunological characteristics of newborn/infant disease. The goal of this pilot project is to establish and optimize a M. tuberculosis "dose-response" infection in newborn and infant macaques to investigate the mechanisms of TB infection in the neonatal macaque model of pediatric AIDS. This information should enhance our basic understanding of disease progression and help to understand the immune responses in TB-infected newborns and infants.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 结核病是全世界艾滋病患者死亡的主要原因，是与艾滋病毒一起发生的最早的机会性感染之一，并且是艾滋病毒复制和随后免疫系统恶化的加速剂。 全世界每年有 100 万儿童新感染结核病 (TB)，42 万儿童新感染艾滋病毒。 结核分枝杆菌和艾滋病毒的双重感染，即“被诅咒的二重唱”，是一个日益严重的全球紧急情况。 尽管在 HIV-1/Mtb 合并感染患者的结核病治疗过程中使用高效抗逆转录病毒疗法可降低死亡率，但也可能危及生命。 迫切需要艾滋病毒/结核分枝杆菌混合感染的猴子模型，以便开发出同时对抗两种病原体的鸡尾酒疗法。 随着针对成人的结核病和艾滋病疫苗的开发，婴儿猴模型对于测试这些疫苗在婴儿（以及可能被动地将免疫力传递给婴儿的孕妇）中的有效性和安全性也将变得重要。 我们在艾滋病婴儿恒河猴模型方面拥有丰富的经验，在结核病成年恒河猴模型方面也拥有丰富的经验。 我们建议建立和优化恒河猴新生儿/婴儿结核感染模型，以表征疾病进展的临床、细菌学和免疫学特征。 这项工作将在我们的 ABSL-3 设施中进行，预计将提供足够的数据来确定剂量，该剂量足以导致结核病逐渐发展，但又不会太高以致动物死亡太快而无法进行实验干预，特别是在同时感染的动物中。 总体目标是建立模拟新生儿/婴儿疾病的临床、细菌学和免疫学特征的新生儿非人灵长类结核病模型。 该试点项目的目标是在新生儿和婴儿猕猴中建立和优化结核分枝杆菌“剂量反应”感染，以研究儿科艾滋病新生儿猕猴模型中的结核感染机制。 这些信息应该增强我们对疾病进展的基本了解，并有助于了解感染结核病的新生儿和婴儿的免疫反应。