A NOVEL SYSTEMIC AND MUCOSAL ADJUVANT FOR BIODEFENSE

一种用于生物防御的新型全身粘膜佐剂

• 批准号: 8172586
• 负责人: ROBERT E. JOHNSTON
• 金额: $ 15.21万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172586
• 关键词: Adjuvant; Avian Influenza; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Exhibits; Francisella tularensis; Funding; Generations; Goals; Grant; Immune response; Inactivated Vaccines; Individual; Infection; Institution; Junin virus; Medicine; Modality; Molecular; Mus; Natural Immunity; Pathway interactions; Poxviridae; Primates; Production; Replicon; Research; Research Personnel; Resources; Rift Valley fever virus; Signal Pathway; Source; Testing; United States National Institutes of Health; Vaccines; Venezuelan Equine Encephalitis Virus; Viral; Virus Diseases; adaptive immunity; base; biodefense; comparative; hemorrhagic fever virus; manufacturing process; member; novel; particle; response

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. The importance of the innate immune response as both the first line of defense against infection and a powerful trigger of adaptive immunity, and the definition of signaling pathways involved with this response, have led to intense testing of individual members of these pathways as molecular adjuvants. However, in the case of viral infection, the complete innate immune response is triggered by the presence of viral particles and their constituent components. Our approach is based on the idea that the viral particle itself, if it could be made safe and applicable to a wide range of vaccine modalities, would be a broad and effective inducer of innate immunity, in other words, an excellent adjuvant. Our studies to date indicate that propagation-defective Venezuelan equine encephalitis virus (VEE) replicon particles safely exhibit potent systemic and mucosal adjuvant activity when administered with subunit or inactivated vaccines. To build on these results with the goal of producing a safe and effective second generation adjuvant for biodefense, we propose the following four aims: Aim 1 - to further define VEE adjuvant activity in mice; Aim 2 - with our collaborators, to test adjuvant activity for specific biodefense vaccines, including avian influenza, poxviruses, Rift Valley Fever virus, Guanarito and Junin hemorrhagic fever viruses, and F. tularensis; Aim 3 - in collaboration with the Center for Comparative Medicine at U.C.-Davis, to determine the level of adjuvant activity in primates; and Aim 4 - to develop a scalable manufacturing process for adjuvant production.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 先天免疫反应是针对感染的第一道防线和适应性免疫的强大触发因素，以及与此反应有关的信号传导途径的定义，导致对这些途径的各个成员作为分子佐剂进行了激烈的测试。但是，在病毒感染的情况下，完全先天免疫反应是由病毒颗粒及其成分的存在触发的。我们的方法基于这样的观念：如果病毒颗粒本身可以使其安全且适用于广泛的疫苗模式，则将是一种宽广有效的先天免疫诱导剂，换句话说，是出色的辅助剂。迄今为止，我们的研究表明，当用亚基或灭活疫苗给药时，传播缺陷的委内瑞拉马脑炎病毒（VEE）复制子颗粒可以安全地表现出有效的全身和粘膜佐剂活性。为了建立这些结果，目的是为BioDefense生产安全有效的第二代佐剂，我们提出以下四个目标：目标1-进一步定义小鼠中的VEE辅助活动； AIM 2-与我们的合作者一起测试辅助活性，以针对特定的生物性疫苗，包括禽流感，poxviruses，Rift Valley Fever病毒，瓜纳里托（Guanarito）和Junin出血性发烧病毒以及F. tolarensis； AIM 3-与U.C. -Davis的比较医学中心合作，以确定灵长类动物的辅助活动水平；目标4-开发辅助生产的可扩展制造过程。