Time-course study of the protection induced by an interferon-inducible DNA vaccine against viral haemorrhagic septicaemia in rainbow trout

Dagoberto Sepúlveda, Ellen Lorenzen, Jesper Skou Rasmussen, Katja Einer-Jensen, Bertrand Collet, C J Secombes, Niels Lorenzen (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

The highly effective DNA vaccines against diseases caused by fish rhabdoviruses in farmed fish consist of a DNA plasmid vector encoding the viral glycoprotein under the control of a constitutive cytomegalovirus promoter (CMV). Among others, attempts to improve efficacy and safety of these DNA vaccines have focused on regulatory elements of plasmid vectors, which play a major role in controlling expression levels of vaccine antigens. Depending on the context, use of a fish-derived promoter with minimal activity in mammalian cells could be preferable. Another aspect related to the CMV promoter is that constitutive expression of the vaccine antigen may lead to rapid elimination of antigen expressing cells in the fish and thereby potentially reduce the long-term effects of the vaccine. In this study, we compared DNA vaccines with the interferon-inducible Mx promoter from rainbow trout and the CMV promoter, respectively. Plasmid constructs encoding the enhanced green fluorescent protein (EGFP) were used for the in vitro analysis, whereas DNA vaccines encoding the glycoprotein (G) of the viral haemorrhagic septicaemia virus (VHSV) were applied for the in vivo examination. The in vitro analysis showed that while the DNA vaccine with the CMV promoter constitutively drove the expression of EGFP in both fish and human cell lines, the DNA vaccine with the Mx promoter inducibly enhanced the expression of EGFP in the fish cell line. To address the impact on protection, a time-course model was followed as suggested by Kurath et al. (2006), where vaccinated fish were challenged with VHSV at 2, 8 and 78 weeks post-vaccination (wpv). The DNA vaccine with the CMV promoter protected at all times, while vaccination with the DNA vaccine containing the Mx promoter only protected the fish at 8 wpv. However, following induction with Poly (I:C) one week before the challenge, high protection was also evident at 2 wpv. In conclusion, the results revealed a more fish host dependent activity of the trout Mx promoter compared to the traditionally used cross species-active CMV promoter, but improvements will be needed for its application in DNA vaccines to ensure long term protection.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalFish & Shellfish Immunology
Volume85
Early online date30 Jun 2018
DOIs
Publication statusPublished - Feb 2019

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Time and motion study
DNA Vaccines
septicemia
vaccine
recombinant vaccines
interferons
Fish
Interferons
rainbow
Oncorhynchus mykiss
promoter regions
DNA
Cytomegalovirus
fish
vaccination
Plasmids
Vaccines
antigen
plasmid
Cells

Keywords

  • Journal Article
  • DNA vaccines
  • Rainbow trout
  • Viral haemorragic seticaemia virus
  • VHSV
  • VHS
  • Antiviral responses
  • Mx
  • Promoter
  • CMV
  • Promoter

Cite this

Time-course study of the protection induced by an interferon-inducible DNA vaccine against viral haemorrhagic septicaemia in rainbow trout. / Sepúlveda, Dagoberto; Lorenzen, Ellen; Rasmussen, Jesper Skou; Einer-Jensen, Katja; Collet, Bertrand; Secombes, C J; Lorenzen, Niels (Corresponding Author).

In: Fish & Shellfish Immunology, Vol. 85, 02.2019, p. 99-105.

Research output: Contribution to journalArticle

Sepúlveda, Dagoberto ; Lorenzen, Ellen ; Rasmussen, Jesper Skou ; Einer-Jensen, Katja ; Collet, Bertrand ; Secombes, C J ; Lorenzen, Niels. / Time-course study of the protection induced by an interferon-inducible DNA vaccine against viral haemorrhagic septicaemia in rainbow trout. In: Fish & Shellfish Immunology. 2019 ; Vol. 85. pp. 99-105.
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