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 Citations (Scopus)

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

Fingerprint

Feline Immunodeficiency Virus
env Genes
Felidae
Virus Diseases
Interleukin-12
Vaccination
Cats
DNA
Gene Expression
Membrane Proteins
Cytotoxic T-Lymphocytes
Gold
Antibodies
Viruses
Proviruses
Polymerase Chain Reaction
Intraperitoneal Injections
Antibody Formation
Immunization
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Boretti, F. S., Leutenegger, C. M., Mislin, C., Hofmann-Lehmann, R., König, S., Schroff, M., ... 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

Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression. / Boretti, Felicitas S.; Leutenegger, Christian M.; Mislin, Caroline; Hofmann-Lehmann, Regina; König, Sven; Schroff, Matthias; Junghans, Claas; Fehr, Daniela; Huettner, Silke W.; Habel, André; Flynn, J. Norman; Aubert, André; Pedersen, Niels C; Wittig, Burghardt; Lutz, Hans.

In: AIDS, Vol. 14, No. 12, 2000, p. 1749-1757.

Research output: Contribution to journalArticle

Boretti, FS, Leutenegger, CM, Mislin, C, Hofmann-Lehmann, R, König, S, Schroff, M, Junghans, C, Fehr, D, Huettner, SW, Habel, A, Flynn, JN, Aubert, A, Pedersen, NC, 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, vol. 14, no. 12, pp. 1749-1757. https://doi.org/10.1097/00002030-200008180-00009
Boretti, Felicitas S. ; Leutenegger, Christian M. ; Mislin, Caroline ; Hofmann-Lehmann, Regina ; König, Sven ; Schroff, Matthias ; Junghans, Claas ; Fehr, Daniela ; Huettner, Silke W. ; Habel, André ; Flynn, J. Norman ; Aubert, André ; Pedersen, Niels C ; Wittig, Burghardt ; Lutz, Hans. / Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression. In: AIDS. 2000 ; Vol. 14, No. 12. pp. 1749-1757.
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T1 - Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression

AU - Boretti, Felicitas S.

AU - Leutenegger, Christian M.

AU - Mislin, Caroline

AU - Hofmann-Lehmann, Regina

AU - König, Sven

AU - Schroff, Matthias

AU - Junghans, Claas

AU - Fehr, Daniela

AU - Huettner, Silke W.

AU - Habel, André

AU - Flynn, J. Norman

AU - Aubert, André

AU - Pedersen, Niels C

AU - Wittig, Burghardt

AU - Lutz, Hans

PY - 2000

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N2 - 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.

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