DNA Vaccines With HIV Virus-like Particles

描述：(申请人提供)艾滋病毒/艾滋病患者面临的问题之一 疫苗是一种保护人类免疫系统中存在的菌株多样性的能力。 患者群体。最保守的序列在 内部结构蛋白。这些保守的序列包含表位 可在主要组织相容性抗原上提呈，提高细胞介导性 免疫，除了体液免疫外，通常由 艾滋病毒/艾滋病疫苗。DNA疫苗可诱导体液免疫和细胞免疫 并可提供对几种病原体的保护作用。然而，DNA 仅表达HIV-1包膜蛋白的疫苗相对 在产生高滴度、持久、中和抗体方面无效 各种动物模型。为了激发高效的免疫反应 HIV-1蛋白，我们建议设计和测试一种表达HIV-1的DNA疫苗 病毒样颗粒(VLP)。这种疫苗的设计是为了既能引发 对猪瘟主要结构蛋白的体液和细胞免疫应答 HIV、Gag和Env基因产物。VLP的安全突变设计为 疫苗以满足美国政府关于疫苗接种的指导方针 人类。表达这些HIV-1 VLP的DNA质粒将被构建和检测 用于在体外高效表达。然后，这些质粒会被接种到 测试HIV-1 Gag和Env蛋白免疫原性的啮齿动物模型系统。 在成功完成这些研究后，第二组DNA表达 将构建密码子优化的VLP构建。此外，一个 泛素-Nef融合基因将被添加到每一个的基因组 密码子优化的DNA VLP疫苗将被测试为增强的 对HIV-1基因产物的免疫原性。

DESCRIPTION: (Provided by Applicant) One of the problems faced by an HIV/AIDS vaccine is the ability to protect against the diversity of isolates present in patient populations. The sequences that are most conserved are found in internal structural proteins. These conserved sequences contain epitopes that can be presented on major histocompatibility antigens to raise cell-mediate immunity, in addition to the humoral immunity that is often elicited by HIV/AIDS vaccines. DNA vaccination can elicit both humoral and cellular immune responses and can confer protection against several pathogens. However, DNA vaccines expressing only the HIV-1 envelope (Env) protein have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies in a variety of animal models. In order to elicit efficient immune responses to HIV-1 proteins, we propose to design and test a DNA vaccine expressing an HIV-1 virus like particle (VLP). This vaccine has been designed to elicit both humoral and cell-mediated immune responses to the major structural proteins of HIV, the Gag and Env gene products. The VLP has safety mutations designed into vaccine in order to meet U.S. government guidelines for vaccination into humans. DNA plasmids expressing these HIV-1 VLPs will be constructed and tested for efficient expression in vitro. Then, these plasmids will be inoculated into rodent model systems to test for immunogenicity to HIV-1 Gag and Env proteins. After successful completion of these studies, a second set of DNA expressing codon-optimized VLP constructs will be constructed. In addition, an ubiquitin-Nef fusion gene will be added to the genome of each of these codon-optimized DNA VLP vaccines and will be tested for elicitation of enhanced immunogenicity to HIV-1 gene products.