A Lentivirus Vaccine for HIV

HIV 慢病毒疫苗

• 批准号: 6746111
• 负责人: Sybille L Sauter
• 金额: $ 27.15万
• 依托单位: VIROGENICS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746111
• 关键词: AIDS vaccines; Lentivirus; antigens; biotechnology; colony stimulating factor; cytokine; cytotoxic T lymphocyte; drug design /synthesis /production; feline immunodeficiency virus; human immunodeficiency virus; immunoglobulin A; laboratory mouse; mucosal immunity; transfection /expression vector; vaccine development

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 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 (HIV gag/pol/tatnf/rev) in a non-human lentiviral system 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 lentivirus HIV vaccine include i) transduction analysis of relevant target cells and organs, ii) expression levels and duration of the immunogen, iii) cellular immune responses t 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靶抗原的选择，即通过使用合适的递送系统诱导对这些抗原的适当免疫反应的能力，以及该病毒是否能够通过遗传适应来逃避这些免疫反应。诱导基于细胞的免疫反应（最著名的是CTL）对多种和保守的抗原的诱导似乎是解决这些问题的核心。与此相一致的是，减毒病毒疫苗接种可以成功保护非人类灵长类动物。 通过基于猫免疫缺陷病毒的非人类慢病毒系统，将开发一种“衰减” HIV疫苗通过在非人类慢病毒系统中纳入完全安全，残疾的HIV免疫原（HIV GAG/POL/TATNF/REV）。该疫苗不仅可以安全地模仿HIV感染，而且会呈现大量的安全病毒基因。同样，该疫苗将通过粘膜途径进行，以最佳诱导粘膜特异性免疫反应。这种方法将使免疫系统能够在HIV感染的门户上产生广泛的基于细胞的免疫反应。此外，由于慢病毒载体的插入能力较大，该疫苗平台具有灵活性，可以包括免疫增强的细胞因子，以确保发展适当的免疫反应。分析慢病毒HIV疫苗功效的研究包括i）i）对相关靶细胞和器官的转导分析，ii）免疫原的表达水平和持续时间，iii）在体外和体内诱导的细胞免疫反应T HIV诱导的细胞免疫反应，以及体内，iv）在小型动物模型中的保护。