A Lentivirus Vaccine for HIV

描述(申请人提供)：最近的研究表明，成功的艾滋病毒疫苗的开发将取决于目标抗原的选择(S)，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，以及病毒是否能够通过基因适应来逃避这些免疫反应。以细胞为基础的免疫反应，尤其是CTL，对多种保守抗原的诱导似乎是解决这些问题的核心。与此相一致的是，观察到减毒病毒疫苗可以成功保护非人类灵长类动物。 通过在以猫免疫缺陷病毒为基础的非人类慢病毒系统中加入完全安全的、无效的艾滋病毒免疫原(艾滋病毒gag/pol/talnf/rev)，将开发出一种“减毒”艾滋病毒疫苗。这种疫苗不仅将安全地模拟艾滋病毒感染，而且将呈现大量安全的病毒基因。此外，这种疫苗将通过粘膜途径接种，以最佳地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入口处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容量很大，该疫苗平台提供了包括免疫增强细胞因子的灵活性，以确保产生适当的免疫反应。将对慢病毒HIV疫苗的有效性进行分析的研究包括：1)相关靶细胞和器官的转导分析；2)免疫原的表达水平和持续时间；3)体外和体内诱导的HIV细胞免疫应答；4)小动物模型对粘膜感染的保护作用。

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.