DNA VACCINATION FOR PREVENTION OF VIRAL, PARASITIC AND MYCOBACTERIAL INFECTION

目的：在多种感染实验模型中，质粒DNA免疫已被证明可诱导保护性免疫。DNA疫苗接种引发MHC I类和II类限制性T细胞反应的能力已被证明是介导这些保护性免疫反应的原因。因此，DNA疫苗接种可以提供一种有用和有效的方法，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，在这些模型中发展对DNA疫苗效用的理解。对于传染病，这包括大利什曼原虫（L. major）、结核分枝杆菌和流感的小鼠模型。此外，这项工作正在应用于灵长类动物的研究，使用DNA作为hiv特异性抗原。这项工作包括鉴定特定感染因子的克隆抗原，并将其克隆成合适的真核表达载体。此外，我们已经获得了一些细胞因子和共刺激分子的DNA，用作特异性抗原的佐剂。DNA纯化后，几周后给小鼠注射并增强。在接种疫苗后的不同时间，老鼠感染了一种特定的病原体。所遵循的参数包括生存、感染负担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，肺结核，细胞免疫，细胞因子，疫苗，CD8+ T细胞，记忆

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