Consortium for AIDS Vaccine Research in Nonhuman Primates

非人灵长类艾滋病疫苗研究联盟

• 批准号: 8704240
• 负责人: Dan H. Barouch
• 金额: $ 788.88万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704240
• 关键词: AIDS Vaccines; Address; Adenovirus Vector; Anatomic Sites; Antibodies; Antibody Formation; Antibody-mediated protection; Attenuated; Autopsy; Biometry; CD8B1 gene; Core Facility; Cytomegalovirus; Data Set; Dependovirus; Development; Event; Goals; HIV-1; Human; Immune; Immune response; Immunologics; Immunology; Infection; Intercept; Intervention; Kinetics; Knowledge; Lead; Life; Macaca mulatta; Mediating; Modality; Modeling; Nature; Pathology; Phase; Prevention; Research; SIV; Services; Site; Specimen; Systems Biology; T-Lymphocyte; Time; Tissues; Vaccine Research; Vaccines; Viral; Virus; Virus Replication; design; improved; insight; neutralizing antibody; next generation; nonhuman primate; novel; poxvirus vectors; programs; simian human immunodeficiency virus; spatiotemporal; tool; transmission process; vaccine development; vector; virology

DESCRIPTION (provided by applicant): The earliest events following mucosal HIV-1 exposure represent a critical window of opportunity for vaccine-elicited immune responses to impact the acquisition and propagation of HlV-1 infection. However, opportunities to elucidate these early immunologic and virologic events in humans are extremely limited. Modeling these events in nonhuman primates will therefore likely be instrumental in the design and development of next generation HIV-1 vaccine strategies. Such studies will provide critical insights into the early events of virus transmission and the capacity of vaccine-elicited immune responses to block or to attenuate these events. In this Consortium, we have assembled many the of world's foremost experts in nonhuman primate research and HIV-1 vaccine development to analyze the virology and immunology of early SIV/SHIV infection in rhesus monkeys as well as to determine the mechanism by which cutting-edge vaccine approaches afford protection in these models. These studies will allow a detailed interrogation of the ability of different types of immune responses to intercept the virus and to control early infection. We hypothesize that certain vaccines and immunologic interventions will be able to attenuate or even abrogate the early events following mucosal SIV/SHIV infection, including the initial local amplification of virus at the mucosal portal of entry as well as the subsequent trajectory of virus spread that leads to systemic dissemination. During the proposed five year project period, we will explore in detail the mechanism of protection afforded by adenovirus vectors and poxvirus vectors (Barouch, Project 1), cytomegalovirus vectors (Picker, Project 2), live attenuated SIV (Johnson, Project 3), neutralizing antibodies (Burton, Project 4), and adeno-associated virus-mediated antibody delivery (Desrosiers, Project 5). These Projects will receive extensive support from the Administrative/Biostatistics (Barouch/Johnson, Core A), Pathology (Haase, Core B), Immunology (Johnson/Burton, Core C), Virology (Shaw/Lifson, Core D), Systems Biology (Sekaly, Core E), and Nonhuman Primate (Axthelm/Mansfield, Core F) core facilities.

描述（由申请人提供）：粘膜HIV-1暴露后的最早事件代表了疫苗引诱的免疫反应的关键机会窗口，以影响HLV-1感染的获取和传播。但是，在人类中阐明这些早期免疫和病毒事件的机会极为有限。因此，在非人类灵长类动物中对这些事件进行建模可能会在下一代HIV-1疫苗策略的设计和开发中发挥作用。此类研究将为病毒传播的早期事件以及疫苗吸收的免疫反应的能力提供关键见解，以阻断或衰减这些事件。在这个财团中，我们汇集了许多世界上最重要的非人类灵长类动物研究和HIV-1疫苗开发专家，以分析恒河猴早期SIV/SHIV感染的病毒学和免疫学，以及确定这些模型中最杰出的疫苗方法可在这些模型中提供保护的机制。这些研究将详细询问不同类型的免疫反应拦截病毒并控制早期感染的能力。我们假设某些疫苗和免疫学干预措施将能够减轻甚至废除粘膜SIV/SHIV感染后的早期事件，包括在入口的粘膜门口中对病毒的最初局部扩增以及随后导致系统性传播的病毒扩散轨迹。 During the proposed five year project period, we will explore in detail the mechanism of protection afforded by adenovirus vectors and poxvirus vectors (Barouch, Project 1), cytomegalovirus vectors (Picker, Project 2), live attenuated SIV (Johnson, Project 3), neutralizing antibodies (Burton, Project 4), and adeno-associated virus-mediated antibody delivery （Desrosiers，项目5）。这些项目将获得行政/生物统计学（Barouch/Johnson，Core A），病理学（HAASE，CORE B），免疫学（Johnson/Burton，Core C），病毒学（Shaw/Lifson，Core D），系统生物学（Sekaly，Core E）和Nonhuman Primate（Axthelm/Manserfeclife core core f）。