title: Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression.
abstract: OBJECTIVE
  To evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors coding for domains of the feline immunodeficiency virus (FIV) env gene and feline 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 vectors. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors expressing FIV surface plus part of the transmembrane protein. In addition, group 3 received feline IL-12 DNA. All cats were challenged by intraperitoneal 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; PCR) and cytotoxic T lymphocyte (CTL) activity (in selected cats).
  
  
  RESULTS
  None of the cats developed a detectable antibody response during immunizations. Four weeks after challenge exposure, all cats in group 1 (control) 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.
  
  
  CONCLUSIONS
  Genetic vaccination using a MIDGE-based construct for the expression 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.
authors.affiliation: Department of Veterinary Internal Medicine, University of Zurich, Switzerland. fboretti@vetklinik.unizh.ch
authors.forename: F S
authors.initials: FS
authors.lastname: Boretti
authors.forename: C M
authors.initials: CM
authors.lastname: Leutenegger
authors.forename: C
authors.initials: C
authors.lastname: Mislin
authors.forename: R
authors.initials: R
authors.lastname: Hofmann-Lehmann
authors.forename: S
authors.initials: S
authors.lastname: König
authors.forename: M
authors.initials: M
authors.lastname: Schroff
authors.forename: C
authors.initials: C
authors.lastname: Junghans
authors.forename: D
authors.initials: D
authors.lastname: Fehr
authors.forename: S W
authors.initials: SW
authors.lastname: Huettner
authors.forename: A
authors.initials: A
authors.lastname: Habel
authors.forename: J N
authors.initials: JN
authors.lastname: Flynn
authors.forename: A
authors.initials: A
authors.lastname: Aubert
authors.forename: N C
authors.initials: NC
authors.lastname: Pedersen
authors.forename: B
authors.initials: B
authors.lastname: Wittig
authors.forename: H
authors.initials: H
authors.lastname: Lutz
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002415:Cats; D004279:DNA, Viral / Q000276:immunology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015752:Genes, env / Q000276:immunology*; D005822:Genetic Vectors; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018664:Interleukin-12 / Q000235:genetics*; D008297:Male; D011533:Proviruses / Q000302:isolation & purification; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000662:veterinary; D019444:Vaccines, DNA; D019562:Viral Load; D014765:Viral Vaccines
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines; D018664:Interleukin-12