A Novel Systemic and Mucosal Adjuvant for Biodefense

一种用于生物防御的新型全身和粘膜佐剂

基本信息

批准号：
7281975
负责人：
ROBERT E. JOHNSTON
金额：
$ 116.62万
依托单位：
GLOBAL VACCINES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7281975
关键词：
Adjuvant Agonist Alphavirus Antigens Attenuated Live Virus Vaccine Avian Influenza Biological Bioterrorism Cells Collaborations Complex Cyclic GMP Development Disadvantaged Disease Dose Encephalitis Viruses Equus caballus Exhibits Francisella tularensis Gene Targeting Generations Genes Genetically Modified Organisms Genome Goals Guanarito virus Immune Immune response Immune system Immunity Immunization Inactivated Vaccines Individual Infection Influenza Interferon Type I Invaded Junin virus Life Macaca Medicine Messenger RNA Methods Modality Molecular Mucosal Immunity Mus Natural Immunity Nature Numbers Organism Ovalbumin Particulate Pathogenesis Pathology Pathway interactions Phase Pick Disease of the Brain Poxviridae Primates Production Proteins RNA replication Range Relative (related person)Replicon Rift Valley fever virus Rodent Route Safety Sampling Serum Signal Pathway Signal Transduction Structural Genes Subunit Vaccines Surrogate Markers System Testing Time Toll-like receptors Transgenes Vaccination Vaccines Variant Venezuelan Equine Encephalitis Virus Venezuelan Equine Encephalomyelitis Viral Viral Structural Proteins Virion Virus Virus Diseases base biodefense comparative cytokine hemorrhagic fever virus in vivo lymph nodes manufacturing process member novel particle pathogen response simian immunodeficiency virus gp120 vaccine development vector vector vaccine

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：先天免疫反应作为抵御感染的第一道防线和适应性免疫的强大触发因素的重要性，以及与该反应相关的信号通路的定义，导致对个体成员进行了严格的测试这些途径作为分子佐剂。然而，在病毒感染的情况下，完整的先天免疫反应是由病毒颗粒及其组成成分的存在触发的。我们的方法基于这样的想法：如果病毒颗粒本身能够安全并适用于多种疫苗模式，那么它将成为一种广泛而有效的先天免疫诱导剂，换句话说，一种极好的佐剂。我们迄今为止的研究表明，当与亚单位疫苗或灭活疫苗一起施用时，繁殖缺陷型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。为了以这些结果为基础，以生产安全有效的第二代生物防御佐剂为目标，我们提出以下四个目标：目标 1 - 进一步确定 VEE 佐剂在小鼠中的活性；目标 2 - 与我们的合作者一起测试特定生物防御疫苗的佐剂活性，包括禽流感、痘病毒、裂谷热病毒、瓜纳里托和胡宁出血热病毒以及土拉热弗朗西斯病毒；目标 3 - 与加州大学戴维斯分校比较医学中心合作，确定灵长类动物的佐剂活性水平；目标 4 - 开发可扩展的佐剂生产制造工艺。