DNA Vaccines With HIV Virus-like Particles

含有 HIV 病毒样颗粒的 DNA 疫苗

• 批准号: 6816855
• 负责人: Ted M Ross
• 金额: $ 20.93万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6816855
• 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：（申请人提供）艾滋病毒/艾滋病所面临的问题之一 疫苗是防止存在的分离物多样性的能力 患者人群。最保守的序列在 内部结构蛋白。这些保守的序列包含表位 可以在主要的组织相容性抗原上呈现以升高细胞中的抗原 免疫，除了经常引起的体液免疫力 艾滋病毒/艾滋病疫苗。 DNA疫苗接种可以引起体液和细胞免疫 反应并可以赋予对多种病原体的保护。但是，DNA 仅表达HIV-1包膜（ENV）蛋白的疫苗已经相对较 在产生高滴度，持久，中和抗体的无效 各种动物模型。为了产生有效的免疫反应 HIV-1蛋白，我们建议设计和测试表达HIV-1的DNA疫苗 病毒之类的粒子（VLP）。这种疫苗旨在引起两者 对主要结构蛋白的体液和细胞介导的免疫反应 艾滋病毒，插科打and和env基因产物。 VLP具有设计为安全突变 疫苗以符合美国政府的疫苗接种指南 人类。将构建和测试表达这些HIV-1 VLP的DNA质粒 在体外有效表达。然后，将这些质粒接种到 啮齿动物模型系统测试对HIV-1 GAG和ENV蛋白的免疫原性。 成功完成这些研究后，第二组DNA表达 将构建对密码子优化的VLP构建体。另外，一个 泛素-nef融合基因将添加到每个基因组中 密码子优化的DNA VLP疫苗，并将测试以促进增强 对HIV-1基因产物的免疫原性。

项目成果

Lentivirus-like particles without reverse transcriptase elicit efficient immune responses.

• DOI: 10.2174/157016206778560018
• 发表时间: 2006-09
• 期刊: Current HIV research
• 影响因子: 1
• 作者: Sean P Mcburney;K. Young;C. Nwaigwe;A. Soloff;K. Cole;T. Ross

Mucosal vaccine vectors: replication-competent versus replication-deficient poxviruses.

粘膜疫苗载体：复制能力与复制缺陷型痘病毒。

• DOI: 10.2174/138161207781039832
• 发表时间: 2007
• 期刊: Current pharmaceutical design
• 影响因子: 3.1
• 作者: Karkhanis,LukenaU;Ross,TedM
• 通讯作者: Ross,TedM

Virus-like particles: designing an effective AIDS vaccine.

• DOI: 10.1016/j.ymeth.2006.05.024
• 发表时间: 2006-09
• 期刊: Methods
• 影响因子: 4.8
• 作者: K. Young;Sean P Mcburney;L. Karkhanis;T. Ross

Elicitation of immunity to HIV type 1 Gag is determined by Gag structure.

对 HIV 1 型 Gag 的免疫力的引发由 Gag 结构决定。

• DOI: 10.1089/aid.2006.22.99
• 发表时间: 2006
• 期刊: AIDS research and human retroviruses.
• 作者: Young,KellyR;Ross,TedM
• 通讯作者: Ross,TedM