DNA VACCINATION FOR PREVENTION OF VIRAL, PARASITIC AND MYCOBACTERIAL INFECTION

用于预防病毒、寄生虫和分枝杆菌感染的 DNA 疫苗接种

• 批准号: 6288990
• 负责人: ROBERT A SEDER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288990
• 关键词: Leishmania major; Mycobacterium tuberculosis; Orthomyxoviridae; active immunization; antibody formation; cytokine; laboratory mouse; protein biosynthesis; vaccine development; vector vaccine

Purpose-Immunization with plasmid DNA has been shown to induce protective immunity in a variety of experimental models of infection. The ability of DNA vaccination to elicit both MHC class I and class II restricted T cell responses has been shown to be responsible for mediating these protective immune responses. Thus, DNA vaccination can provide a useful and an effective way in providing effective immunity to particular pathogens depending on the type of immunity required for protection. We have identified a number of murine experimental models in which to develop an understanding for the utility of DNA vaccination. For infectious diseases, this includes murine models for Leishmania major (L. major), Mycobacterium tuberculosis and Influenza. In addition this work is being applied to primate studies using DNA for HIV-specific antigens. The work involves identifying cloned antigens for the specific infectious agent and cloning it into an appropriate euykaryotic expression vector. In addition, we have obtained DNA for a number of cytokines and costimulatory molecules to be used as adjuvants to the specific antigens. Following purification of the DNA, mice are then injected and boosted several weeks later. At various times following the vaccination, mice are infected with a particular pathogen. Parameters that are followed include survival, quantitation of infectious burden, and immunologic studies of antibody and cytokine production. - Leishmania, HIV, Tuberculosis, Cellular Immunity, Cytokines, Vaccines, CD8+ T Cells, Memory

目的-质粒 DNA 免疫已被证明可以在多种感染实验模型中诱导保护性免疫。 DNA 疫苗接种能够引发 MHC I 类和 II 类限制性 T 细胞反应，已被证明负责介导这些保护性免疫反应。因此，DNA疫苗接种可以提供一种有用且有效的方法，根据保护所需的免疫类型，对特定病原体提供有效的免疫力。我们已经确定了许多小鼠实验模型，以加深对 DNA 疫苗接种效用的了解。对于传染病，这包括重大利什曼原虫（L.major）、结核分枝杆菌和流感的小鼠模型。此外，这项工作还被应用于使用 DNA 检测 HIV 特异性抗原的灵长类动物研究。这项工作包括鉴定特定感染因子的克隆抗原，并将其克隆到适当的真核表达载体中。此外，我们还获得了许多细胞因子和共刺激分子的DNA，可用作特定抗原的佐剂。 DNA 纯化后，几周后对小鼠进行注射和加强免疫。接种疫苗后的不同时间，小鼠会感染特定的病原体。随后的参数包括存活率、感染负荷的定量以及抗体和细胞因子产生的免疫学研究。 - 利什曼原虫、HIV、结核病、细胞免疫、细胞因子、疫苗、CD8+ T 细胞、记忆