A Lentivirus Vaccine for HIV

描述(由申请人提供)：最近的研究表明， 开发一种成功的艾滋病毒疫苗将取决于目标的选择 抗原(S)，诱导对这些病毒的适当免疫反应的能力 通过使用合适的抗原传递系统，以及病毒是否 能够通过基因适应来逃避这些免疫反应。归纳法 以细胞为基础的免疫反应，尤其是CTL，对多重和保守的 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地保护 非人灵长类动物。 一种“减毒”的艾滋病毒疫苗将通过将一种 在非人类慢病毒中安全、禁用的HIV免疫原(HIVgag/Poll/talnf/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，而且会呈现出广泛的 安全的病毒基因。此外，这种疫苗将通过粘膜途径接种。 以最佳方式诱导粘膜特异性免疫反应。这种方法将允许 免疫系统产生广泛基于细胞的免疫反应 艾滋病毒感染的门户。此外，由于插入容量较大， 慢病毒载体，这个疫苗平台提供了灵活性，包括 免疫增强型细胞因子确保适当免疫的发展 回应。将进行的分析Lenti-HIV有效性的研究包括 I)相关靶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)对艾滋病毒的细胞免疫反应 在体外和体内诱导，以及iv)对小鼠粘膜感染的保护作用 小动物模型。

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.