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

Felicitas S. Boretti, Christian M. Leutenegger, Caroline Mislin, Regina Hofmann-Lehmann, Sven König, Matthias Schroff, Claas Junghans, Daniela Fehr, Silke W. Huettner, André Habel, J. Norman Flynn, André Aubert, Niels C Pedersen, Burghardt Wittig, Hans Lutz

Research output: Contribution to journalArticle

33 Scopus citations

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. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)1749-1757
Number of pages9
JournalAIDS
Volume14
Issue number12
DOIs
StatePublished - 2000

Keywords

  • DNA vaccine
  • Feline IL-12
  • FIV env gene
  • Protection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Boretti, F. S., Leutenegger, C. M., Mislin, C., Hofmann-Lehmann, R., König, S., Schroff, M., Junghans, C., Fehr, D., Huettner, S. W., Habel, A., Flynn, J. N., Aubert, A., Pedersen, N. C., Wittig, B., & Lutz, H. (2000). Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression. AIDS, 14(12), 1749-1757. https://doi.org/10.1097/00002030-200008180-00009