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免疫已被证明在各种实验感染模型中诱导保护性免疫。DNA疫苗接种引发MHC I类和II类限制性T细胞应答的能力已被证明是介导这些保护性免疫应答的原因。因此，DNA疫苗接种可以提供一种有用和有效的方式，根据保护所需的免疫类型，提供对特定病原体的有效免疫。我们已经确定了一些小鼠实验模型，在其中开发的DNA疫苗接种的效用的理解。对于感染性疾病，这包括用于硕大利什曼原虫（L.主要），结核分枝杆菌和流感。此外，这项工作正在应用于灵长类动物的研究，使用DNA的艾滋病毒特异性抗原。这项工作包括鉴定特异性感染因子的克隆抗原，并将其克隆到合适的真核表达载体中。此外，我们已经获得了许多细胞因子和共刺激分子的DNA，可用作特异性抗原的佐剂。在DNA纯化后，小鼠然后被注射并在几周后加强。在疫苗接种后的不同时间，小鼠感染特定病原体。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，CD 8 + T细胞，记忆