Human Immunodeficiency Virus Type 1 Gag- Specific Vaginal Immunity and Protection after Local Immunizations with Sindbis Virus- Based

+T cell‐ mediated responses were detected locally, in the vaginal mucosa and in the draining iliac lymph nodes (ILNs), and systemically, in the spleen. However, the mice were not protected against VV-Gag replication in the ovaries. In contrast, after vaginal or rectal immunization with SIN-Gag and vaginal challenge with VV-Gag, despite lower local CD8 + T cell‐ mediated responses in the vaginal mucosa and ILNs, the mice were protected against VVGag replication in the ovaries. Therefore, local immunization with SIN-Gag induced both local mucosal cell‐ mediated responses and protection. Worldwide, most human immunodeficiency virus (HIV) infections occur through vaginal and rectal transmission [1]. An important role in the control of HIV infection and protection against AIDS has been established for systemic cell-mediated immune responses against HIV-1 Gag [2, 3]. Moreover, evidence suggests that the virus first enters through a mucosal site and then spreads rapidly to distant mucosal and systemic lymphoid and nonlymphoid tissues [4, 5]. Therefore, local immune responses and protection from viral dissemination from the vaginal tract are important. Virus-based genetic delivery systems that induce cellmediated responses in mucosal and systemic lymphoid tissues and that are nonreplicating and lack the ability to revert to an infectious state are of both practical and scientific interest. Alphaviruses, including Sindbis virus (SIN), are enveloped RNA viruses that have been developed into replication-defective “suicide” vectors [6]. SIN vectors that express HIV-1 Gag (SIN-Gag) have been constructed in both plasmid-based [7] and particle-based [8] delivery formats. In this study, we sought to determine which routes of mucosal and systemic immunization with particle-based SIN-Gag conferred protection against vaginal challenge with vaccinia virus (VV) that also expressed HIV1 Gag (VV-Gag). Moreover, we sought a correlation between the observed protection and the magnitude of local and systemic CD8 + T cell‐mediated interferon (IFN)‐g responses, particularly in the effector site of the vaginal mucosa.