DNA Vaccines With HIV Virus-like Particles

描述：（申请人提供）艾滋病毒/艾滋病面临的问题之一 疫苗是针对存在于 患者人群。最保守的序列发现于 内部结构蛋白这些保守序列含有表位， 可以在主要组织相容性抗原上呈递， 免疫力，除了体液免疫，这是经常引起的 艾滋病毒/艾滋病疫苗DNA疫苗可同时诱导体液免疫和细胞免疫 反应，并可以提供保护，对几种病原体。但DNA 仅表达HIV-1包膜（Env）蛋白的疫苗已经相对 在产生高滴度、持久的中和抗体方面无效， 各种动物模型。为了引发有效的免疫反应， HIV-1蛋白，我们建议设计和测试一种表达HIV-1蛋白的DNA疫苗。 病毒样颗粒（VLP）。这种疫苗的设计目的是 体液和细胞介导的免疫反应的主要结构蛋白， HIV，Gag和Env基因产物。VLP具有安全突变设计， 疫苗，以满足美国政府的疫苗接种指南， 人类将构建和检测表达这些HIV-1 VLP的DNA质粒 用于体外高效表达。然后，将这些质粒接种到 啮齿动物模型系统，以测试对HIV-1 Gag和Env蛋白的免疫原性。 在成功完成这些研究后，第二组DNA表达 构建密码子优化的VLP构建体。此外， 泛素-Nef融合基因将被添加到这些基因组中的每一个中， 密码子优化的DNA VLP疫苗，并将进行测试，以激发增强 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.