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 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.
Boretti
F S
FS
Department of Veterinary Internal Medicine, University of Zurich, Switzerland. fboretti@vetklinik.unizh.ch
Leutenegger
C M
CM
Mislin
C
C
Hofmann-Lehmann
R
R
König
S
S
Schroff
M
M
Junghans
C
C
Fehr
D
D
Huettner
S W
SW
Habel
A
A
Flynn
J N
JN
Aubert
A
A
Pedersen
N C
NC
Wittig
B
B
Lutz
H
H
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
D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines; D018664:Interleukin-12