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.
