Human immunodeficiency virus type 1 Gag-specific vaginal immunity and protection after local immunizations with Sindbis virus-based replicon particles

The majority of human immunodeficiency virus (HIV) infections occur through vaginal and rectal transmission. In seeking a safe, nonreplicating gene-de livery vector that can induce mucosal and systemic immune responses and pro tection, Sindbis virus-based replicon particles expressing HIV-1 Gag (SIN-G ag) were developed. In mice, after nasal or intramuscular immunization with SIN-Gag and vaginal challenge with vaccinia virus (VV) expressing HIV-1 Ga g (VV-Gag), CD8(+) T cell-mediated responses were detected locally, in the vaginal mucosa and in the draining iliac lymph nodes (ILNs), and systemical ly, in the spleen. However, the mice were not protected against VV-Gag repl ication in the ovaries. In contrast, after vaginal or rectal immunization w ith 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 prot ected against VV-Gag replication in the ovaries. Therefore, local immunizat ion with SIN-Gag induced both local mucosal cell-mediated responses and pro tection.