A Lentivirus Vaccine for HIV

描述（由申请人提供）：最近的研究清楚地表明，成功的HIV疫苗的开发将取决于目标抗原的选择，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遗传适应逃避这些免疫反应。诱导基于细胞的免疫反应，尤其是CTL，对多种和保守的抗原似乎是解决这些问题的核心。与此一致的观察结果是，减毒病毒疫苗可以成功地保护非人类灵长类动物。

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.