Immune responses against SIV envelope glycoprotein, using recombinant SV40 as a vaccine delivery vector

Vaccination protocols using viral gene delivery vectors have often generated relatively weak responses, largely owing to difficulties in boosting immune responses effectively following the primary injection. Because recombinant gene delivery vectors derived from SV40 permit multiple inoculations, to yield incremental immune responses, we tested the use of rSV40s to deliver lentiviral envelope antigens for immunization. An rSV40 carrying SIVmac239 envelope glycoprotein gp130 cDNA (SV(gp130)) was given multiple times to BALB/c mice, with or without a prior priming inoculation using vaccinia virus carrying the same SIV envelope cDNA (VVenvSIV). Sera from these mice were tested for antibodies binding gp130, applying a novel cell-based ELISA protocol that used as targets cloned P815 cells stably transfected with plasmid-derived gp130 cDNA. The same gp130-expressing clone of P815 cells, labeled with 51Cr was used as targets for direct lymphocyte-mediated cytolytic assays using spleen and popliteal lymph node cells as effectors. After six inoculations with SV(gp130), mice made detectable anti-gp130 antibody responses, but high levels of splenic and popliteal lymph node cytotoxic activity were apparent after as few as three injections of SV(gp130) (>40% specific lysis). A single primary inoculation with VVenvSIV preceding SV(gp130) boosts significantly enhanced antibody responses against SIV gp130, but had little effect on cytotoxic lymphocyte responses. Thus, rSV40 vectors may be useful vehicles for delivering lentiviral envelope antigens to elicit protective humoral and cell-mediated immune responses.