A Lentivirus Vaccine for HIV

HIV 慢病毒疫苗

• 批准号: 6409274
• 负责人: Sybille L Sauter
• 金额: $ 26.25万
• 依托单位: CORAUTUS GENETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6409274
• 关键词: AIDS vaccines; Lentivirus; attenuated microorganism; cellular immunity; chemokine; cytotoxic T lymphocyte; dendritic cells; drug delivery systems; drug screening /evaluation; enzyme linked immunosorbent assay; feline immunodeficiency virus; gene expression; genetic transduction; helper T lymphocyte; humoral immunity; immunologic memory; laboratory mouse; nonhuman therapy evaluation; transfection /expression vector; vaccine development; vector vaccine; virus antigen

DESCRIPTION (Provided by applicant): Recent research has made it clear that the development of a successful HIV vaccine will depend on the choice of target antigen(s), the ability to induce appropriate immune responses to these antigens through the use of a suitable delivery system, and whether the virus is able to escape these immune responses by genetic adaptations. The induction of cellular-based immune responses, most notably CTL, to multiple and conserved viral antigens appears central to addressing these issues. Consistent with this is the observation that attenuated virus vaccination can successfully protect non-human primates. An "attenuated" HIV vaccine will be developed by incorporating a completely safe, disabled HIV immunogen (HIVgag/pol/tatnf/rev) in a non-human lentiviral system (Lenti-HIV) based on the feline immunodeficiency virus. This vaccine will not only safely mimic HIV infection, but will present a broad number of safe viral genes. Also, this vaccine will be administered via a mucosal route to optimally induce mucosal specific immune responses. This approach will allow the immune system to generate a broad cellular based immune response at the portals of HIV infection. In addition, due to the large insert capacity of lentiviral vectors, this vaccine platform offers the flexibility to include immune enhancing cytokines to ensure the development of appropriate immune responses. Studies to be conducted analyzing the efficacy of Lenti-HIV include i) transduction analysis of relevant target cells and organs, ii) expression levels and duration of the immunogen, iii) cellular immune responses to HIV induced in vitro and in vivo, and iv) protection against mucosal infection in a small animal model.

描述（由申请人提供）：最近的研究明确表明 成功的HIV疫苗的开发将取决于目标的选择 抗原，能够诱导对这些反应的适当免疫反应的能力 通过使用合适的输送系统以及病毒是否使用抗原 能够通过遗传适应来避免这些免疫反应。诱导 基于细胞的免疫反应，最著名的CTL，对多个和保守 病毒抗原似乎是解决这些问题的核心。与此一致 是否观察到减毒病毒疫苗可以成功保护 非人类灵长类动物。 通过完全合并一个“衰减”的HIV疫苗 非人类慢病毒中的安全，残疾的HIV免疫原（HIVGAG/POL/TATNF/REV） 基于猫免疫缺陷病毒的系统（Lenti-HIV）。这种疫苗 不仅会安全地模仿艾滋病毒感染，而且会呈现大量 安全病毒基因。此外，该疫苗将通过粘膜途径进行管理 最佳诱导粘膜特异性免疫反应。这种方法将允许 免疫系统在 艾滋病毒感染的门户。另外，由于插入能力的大量 慢病毒向量，该疫苗平台提供了灵活性 免疫增强细胞因子以确保发展适当的免疫 回答。进行分析Lenti-HIV功效的研究包括 i）相关目标细胞和器官的转导分析，ii）表达 免疫原的水平和持续时间，iii）对HIV的细胞免疫反应 诱导体外和体内，以及iv）防止粘膜感染的保护 小动物模型。