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

AIDS. 2000 Aug 18;14(12):1749-57. doi: 10.1097/00002030-200008180-00009.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Cats
  • DNA, Viral / immunology
  • Feline Acquired Immunodeficiency Syndrome / immunology
  • Feline Acquired Immunodeficiency Syndrome / prevention & control*
  • Genes, env / immunology*
  • Genetic Vectors
  • Immunodeficiency Virus, Feline / genetics
  • Immunodeficiency Virus, Feline / immunology*
  • Immunodeficiency Virus, Feline / isolation & purification
  • Interleukin-12 / genetics*
  • Male
  • Proviruses / isolation & purification
  • Random Allocation
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Cytotoxic / immunology
  • Time Factors
  • Vaccination / veterinary
  • Vaccines, DNA*
  • Viral Load
  • Viral Vaccines*

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Vaccines, DNA
  • Viral Vaccines
  • Interleukin-12