Development of a vaccine for Ebola virus in plant system

在植物系统中开发埃博拉病毒疫苗

• 批准号: 6818636
• 负责人: Charles Joel Arntzen
• 金额: $ 57.64万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6818636
• 关键词: Ebola virus; Macaca fascicularis; active immunization; cooperative study; gene expression; genetically modified plants; glycoproteins; monoclonal antibody; plant proteins; protein metabolism; recombinant proteins; vaccine development; vaccine evaluation; viral vaccines; virus diseases; virus protein

DESCRIPTION (provided by applicant): There are no vaccines to prevent infections by Ebola virus, although it is among one of the most feared pathogens worldwide. The research proposed herein will advance development of vaccine candidates, with emphasis on technology that will create pilot lots of vaccine for preclinical testing and cost-saving scale-up capability using transgenic plants for safe production of strategic vaccine reserves. The proposed research exploits the facile capacity of plant cells to express and accumulate complex proteins that are not currently available via other expression systems. The research builds upon an ongoing funding investment by DoD directed to the creation of a "cocktail" of monoclonal antibodies (MAbs) to use in post-exposure prophylaxis for Ebola virus infections; the DoD project utilizes transgenic plants because plant-derived MAbs can be rapidly expanded in commercial production without high-capital cost investments for traditional MAb production facilities. Recent research has shown that MAbs expressed in plant cells can be created as fusion molecules with antigenic protein domains as a C-terminal extension of the constant region of the antibody heavy chain. Highly immunogenic recombinant immune complexes (RICs) form when the variable region of the MAb recognizes the antigenic region of the fusion molecule. We will utilize three different MAbs to create RICs containing the sequences of the Ebola virus glycoprotein (GP) as well as GP fusions. Prototype vaccines will be produced in quantities sufficient for preclinical trials. Industrial participants of the application will develop purification technology for injected vaccines. An existing murine model will be utilized for immunogenicity and challenge trials, which will be followed by non-human primate vaccine evaluation of the lead vaccine candidates.

描述（由申请人提供）：尽管埃博拉病毒是全世界最可怕的病原体之一，但尚无疫苗可以预防埃博拉病毒感染。本文提出的研究将推进候选疫苗的开发，重点是创建用于临床前测试的试点批次疫苗的技术，以及使用转基因植物安全生产战略疫苗储备的节省成本的扩大能力。拟议的研究利用了植物细胞表达和积累复杂蛋白质的简便能力，而这些蛋白质目前无法通过其他表达系统获得。该研究建立在国防部持续资助的基础上，该投资旨在创建单克隆抗体（MAb）“混合物”，用于埃博拉病毒感染的暴露后预防；国防部项目利用转基因植物，因为植物源性单克隆抗体可以在商业生产中迅速扩大，而无需对传统单克隆抗体生产设施进行高资本成本投资。最近的研究表明，在植物细胞中表达的单克隆抗体可以作为融合分子，其抗原蛋白结构域作为抗体重链恒定区的 C 端延伸。当 MAb 的可变区识别融合分子的抗原区时，就会形成高免疫原性的重组免疫复合物 (RIC)。我们将利用三种不同的 MAb 来创建含有埃博拉病毒糖蛋白 (GP) 序列以及 GP 融合体的 RIC。原型疫苗的生产数量将足以进行临床前试验。该应用的工业参与者将开发注射疫苗的纯化技术。现有的小鼠模型将用于免疫原性和激发试验，随后将对主要候选疫苗进行非人灵长类疫苗评估。