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222 SV40 as a Vaccine Delivery Vector for Immunization against SIV Envelope Glycoprotein
H. McKee* and D. Strayer
Jefferson Med. Coll., Philadelphia, PA, USA
Background: Vaccination against lentiviruses remains a challenge, partially because of difficulties in boosting immune responses following primary injection. Since recombinant SV40 vectors (rSV40) are effective gene delivery vehicles and also permit multiple inoculations to generate incremental immune responses, we tested the hypothesis that such a vector could be used to deliver SIVgp130 to mice in order to elicit gp130-specific immune responses.
Methods: An rSV40 carrying the coding sequences for SIVmac239 envelope glycoprotein gp130 (SVgp130), was used to inoculate BALB/c mice every 4 weeks. Sera were collected every 2 weeks and tested by a novel cell-based ELISA (CELISA) for antibodies binding gp130 using a stably transfected clone of P815 cells expressing plasmid-derived gp130 as targets in the assay. The same gp130-expressing clone, labeled with 51Cr, was used as a target to assay gp130-specific cytotoxic T lymphocyte (CTL)-mediated lysis by unselected splenic and popliteal lymph node (PLN) CTL from immunized mice. The efficacy of first immunizing with a vaccinia virus vector encoding the same SIV envelope cDNA as SVgp130 (VVenvSIV), followed by boosting inoculations with SVgp130 was compared with an immunization regimen using SVgp130 alone.
Results: Very strong CTL responses were seen with as few as 3 inoculations of SVgp130 (~40% specific lysis). Greater specific lysis (50(70%) was seen after further inoculations with SVgp130 or following a primary inoculation with VVenvSIV plus 1 or more boosts with SVgp130. High levels of serum anti-gp130 antibody were seen after 6 inoculations with SVgp130. Stronger, faster antibody responses against gp130-expressing target cells were also achieved by priming with VVenvSIV followed by 2 or more boosts with SVgp130.
Conclusions: rSV40 vectors may be useful vehicles for delivering SIVgp130 in vivo, with the ultimate goal of eliciting humoral and cell-mediated immune responses against SIV envelope glycoprotein antigens. These results merit further study of rSV40 as a vector for lentiviral vaccine development.
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