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）：最近的研究表明， 研制成功的艾滋病毒疫苗将取决于靶点的选择 抗原，诱导对这些抗原的适当免疫应答的能力， 抗原通过使用合适的输送系统，以及病毒是否 能够通过遗传适应逃避这些免疫反应。感应 基于细胞的免疫反应，最明显的是CTL，对多种和保守的 病毒抗原似乎是解决这些问题的核心。符合本 减毒病毒疫苗可以成功地保护 非人类灵长类动物 一种“减毒”艾滋病毒疫苗将通过将一种完全 在非人慢病毒中安全的失活HIV免疫原（HIVgag/pol/tatnf/rev） Lenti-HIV是一种基于猫免疫缺陷病毒的系统。这种疫苗 不仅能安全地模拟HIV感染， 安全的病毒基因此外，该疫苗将通过粘膜途径接种 以最佳地诱导粘膜特异性免疫应答。这种方法将允许 免疫系统产生广泛的基于细胞的免疫应答， HIV感染的门户。此外，由于大的插入容量， 慢病毒载体，这种疫苗平台提供了灵活性，包括 免疫增强细胞因子，以确保适当的免疫发展 应答将要进行的分析慢病毒-艾滋病毒功效的研究包括 i）相关靶细胞和器官的转导分析， 免疫原的水平和持续时间，iii）对HIV的细胞免疫应答 在体外和体内诱导，和iv）保护抗粘膜感染， 小动物模型。