Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression

Objective: To evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors codin g for domains of the feline immunodeficiency virus (FIV) env gene and felin e IL-12. Methods: Three groups of four cats each were immunized three times within 6 weeks by the ballistic transfer of gold particles coated with MIDGE vector s. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors exp ressing FIV surface plus part of the transmembrane protein. In addition, gr oup 3 received feline IL-12 DNA. All cats were challenged by intraperitonea l injection of 25 TCID50 of infectious FIV Z2. The following criteria were monitored: clinical signs, antibodies to transmembrane protein, antibodies to whole FIV, haematological parameters and kinetics of CD4 and CD8 cells, FIV proviral load (determined by quantitative polymerase chain reaction; PC R) and cytotoxic T lymphocyte (CTL) activity (in selected cats). Results: None of the cats developed a detectable antibody response during i mmunizations. Four weeks after challenge exposure, all cats in group 1 (con trol) and group 2 (FIV surface-transmembrane protein) had seroconverted and showed a high proviral load until week 19 (end of experiment). In contrast , only one of four cats in group 3 (surface-transmembrane protein and IL-12 ) showed antibodies; it was provirus positive at reduced virus load. Short- lived CTL activity was found in two cats in group 3. Conclusion: Genetic vaccination using a MIDGE-based construct for the expre ssion of the surface-transmembrane protein domain of FIV env and feline IL- 12 DNA led to protection against homologous virus challenge in three out of four vaccinated cats. (C) 2000 Lippincott Williams & Wilkins.