DNA Vaccines With HIV Virus-like Particles

含有 HIV 病毒样颗粒的 DNA 疫苗

• 批准号: 6450554
• 负责人: Ted M Ross
• 金额: $ 20.93万
• 依托单位: EAST CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6450554
• 关键词: AIDS vaccines; HIV envelope protein; antigen antibody reaction; antigens; autoradiography; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; gag protein; human immunodeficiency virus 1; immunization; immunoglobulin G; laboratory mouse; laboratory rabbit; messenger RNA; neutralizing antibody; serum; transfection; vaccine development; vector vaccine; viruslike particle

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.

描述：（由申请人提供）艾滋病毒/艾滋病患者面临的问题之一 疫苗是针对存在于其中的分离株多样性提供保护的能力 患者人群。最保守的序列位于 内部结构蛋白。这些保守序列含有表位 可以呈递在主要组织相容性抗原上以提高细胞介导 除了通常引起的体液免疫外，还具有免疫功能 艾滋病毒/艾滋病疫苗。 DNA疫苗接种可引发体液免疫和细胞免疫 反应并可以针对多种病原体提供保护。然而，DNA 仅表达 HIV-1 包膜 (Env) 蛋白的疫苗相对较 不能有效地产生高滴度、持久的中和抗体 多种动物模型。为了引发有效的免疫反应 HIV-1 蛋白，我们建议设计并测试表达 HIV-1 的 DNA 疫苗 病毒样颗粒（VLP）。该疫苗的设计目的是激发 对主要结构蛋白的体液和细胞介导的免疫反应 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。将构建并测试表达这些 HIV-1 VLP 的 DNA 质粒 用于体外有效表达。然后，将这些质粒接种到 用于测试 HIV-1 Gag 和 Env 蛋白免疫原性的啮齿动物模型系统。 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 构建体。此外，一个 泛素-Nef融合基因将被添加到这些基因组中 密码子优化的 DNA VLP 疫苗并将进行增强诱导测试 HIV-1基因产物的免疫原性。