Protective immunity against feline immunodeficiency virus induced by inoculation with vif-deleted proviral DNA

To determine whether live-attenuated feline immunodeficiency virus (FIV) pr oviral DNA will induce protective immunity, a plasmid clone constructed wit h a FIV provirus containing a deletion in the viral accessory gene vif (FIV -pPPR-Delta vif) was inoculated as proviral DNA into four cats by the intra muscular route. After 43 weeks, these cats were boosted with the same provi ral plasmid. Analysis of peripheral blood mononuclear cells at several time points after the primary and booster inoculations revealed no detectable v irus or proviral DNA. Al 6 weeks after the booster, immunized cats and addi tional naive control cats were challenged with a cell-free preparation of t he infectious biological isolate FIV-PPR by the intraperitoneal route. Viru s was detected after challenge in unvaccinated control cats but not in any of the FIV-pPPR-Delta vif-immunized cats. Both FIV Gag- and Env-specific cy totoxic T lymphocyte (CTL) activities were detected in peripheral blood cel ls of control cats after challenge infection, whereas only one of four cats immunized with FIV-pPPR-Delta vif DNA exhibited a measurable CTL response to Env following challenge. Although anti-Gag antibodies were not detected after both proviral DNA inoculation and challenge, anti-Env antibodies were found in FIV-pPPR-ilvif-immunized cats after vaccination as well as after challenge. These findings indicate that inoculation with FIV-pPPR-Delta vif proviral DNA induced resistance to challenge with infectious FIV and that a vif deletion mutant may provide a relatively safe attenuated lentiviral v accine. (C) 2000 Academic Press.