PLASMID DNA TO INDUCE IMMUNITY TO INTRACELLULAR PATHOGEN

质粒 DNA 诱导细胞内病原体免疫

• 批准号: 2005338
• 负责人: Kenneth A Cornell
• 金额: $ 10万
• 依托单位: INTERLAB CORPORATION
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1997-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2005338
• 关键词: Listeria; bacterial DNA; bacterial proteins; cell mediated lymphocytolysis test; cellular immunity; cytotoxic T lymphocyte; drug screening /evaluation; immunocytochemistry; laboratory mouse; method development; plasmids; southern blotting; transfection; transfection /expression vector; vaccine development; vector vaccine; virulence

A new method of immunization for the control of infectious diseases in which naked plasmid DNA is injected as the "immunogen" has been tested in a limited number of viral models and the results of these initial studies have caused much excitement. For example, immunization with plasmid DNA encoding either the nucleoprotein or hemagglutinin proteins of the influenza virus elicits an immune response which specifically protects against subsequent flu virus challenge. Thus plasmid DNA immunization promises to offer a unique method of stimulating both cellular and humoral immune responses and it represents an attractive alternative to conventional approaches of vaccine development. Indeed, the ability to induce a specific cell mediated immune response is as yet an unfulfilled goal of many vaccine formulations acceptable for clinical use. This is a critical consideration in vaccine development. as a cell mediated immune response is required for the elimination of most intracellular pathogens. While DNA vaccination has proven to be successful for selected viral pathogens, DNA vaccination needs to be assessed for its applicability to pathogens such as intracellular bacteria and fungi for which a heightened cell mediated immunity is required for pathogen control. This application is designed to evaluate the general method of DNA vaccination using a well established model of immunity, to Listeria monocytogenes, a bacterium which is used as a prototype for the analysis of immunity to many intracellular pathogens. Immunity to this intracellular parasite is dependent on a cellular immune mechanism. Thus, we will evaluate DNA immunization especially within the context of cellular immunity, since the failure to stimulate an effective cellular immune response is a general shortcoming of nonviable vaccine formulations. PROPOSED COMMERCIAL APPLICATIONS: Immunization employing plasmid DNA promises to offer a general method for the stimulation of immunity especially a specific cell-mediated immune response. For many bacterial and fungal pathogens that can reside within an intracellular environment, no suitable vaccine exists. Although L. monocytogenes is a intracellular pathogen of limited concern to the general human population it does cause disease and death in individuals with reduced immune capacity. In addition it significantly impacts the sheep and cattle industry. Thus, a DNA vaccine for a well studied intracellular parasite has direct commercial value and may offer greater value as a demonstration of the general utility of DNA vaccine for other bacterial and fungal diseases.

一种新的免疫方法，用于控制传染病， 将裸质粒DNA作为“免疫原”注射， 有限数量的病毒模型和这些初步研究的结果 引起了很大的轰动例如，用质粒DNA免疫 编码核蛋白或血凝素蛋白的蛋白质， 流感病毒激发免疫反应， 抵抗随后的流感病毒攻击。因此质粒DNA免疫 有望提供一种刺激细胞和体液的独特方法， 它代表了一种有吸引力的替代方案， 疫苗开发的传统方法。事实上， 诱导特异性细胞介导免疫应答是迄今尚未实现的 许多疫苗制剂可用于临床使用的目标。这是一 疫苗开发中的重要考虑因素。作为细胞介导的免疫 消除大多数细胞内病原体需要应答。 虽然DNA疫苗已被证明是成功的选择病毒 病原体，DNA疫苗接种需要评估其适用性， 病原体如细胞内细菌和真菌， 病原体控制需要细胞介导的免疫。本申请 设计用于评价使用微孔进行DNA疫苗接种的一般方法 建立免疫模型，单核细胞增生李斯特菌，一种细菌， 被用作分析对许多细胞内 病原体对这种细胞内寄生虫的免疫力取决于 细胞免疫机制因此，我们将评估DNA免疫 特别是在细胞免疫的背景下，由于未能 刺激有效细胞免疫应答是一个普遍的缺点 不可行的疫苗配方。 拟议的商业应用：使用质粒DNA的免疫 有望提供一种刺激免疫力的通用方法 特别是特异性细胞介导的免疫应答。对于许多细菌和 真菌病原体可以驻留在细胞内环境中，不 存在合适的疫苗。虽然L.单核细胞增多症是细胞内 它确实引起的对一般人群关注有限的病原体 免疫能力下降的个体的疾病和死亡。 此外 这对牛羊业产生了重大影响。 因此，DNA 一种研究充分的细胞内寄生虫的疫苗， 价值，并可能提供更大的价值，作为一般效用的演示 其他细菌和真菌疾病的DNA疫苗。