Evidence map›Paper›PMID 25700279›Full record

ArticlePLoS pathogens2015

Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging.

Maxime Boutier, Maygane Ronsmans, Ping Ouyang, Guillaume Fournier, Anca Reschner, Krzysztof Rakus, Gavin S Wilkie, Frédéric Farnir, Calixte Bayrou, François Lieffrig and 4 more

Erratum issuedAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

  1. Article
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  8. Review
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  11. Article
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  15. Article
  16. Betanodavirus and VER Disease: A 30-year Research Review.Pathogens (Basel, Switzerland) · 2020
    Review
  17. Article
  18. Viruses · 2019
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Maxime BoutierImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Maygane RonsmansImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Ping OuyangImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Guillaume FournierImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Anca ReschnerImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Krzysztof RakusImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Gavin S WilkieMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Frédéric FarnirBiostatistics and Bioinformatics, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Calixte BayrouPathology, Department of Morphology and Pathology, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
François LieffrigFish Pathology Lab, Department of Biotechnology, CER Groupe, Marloie, Belgium.
Hong LiUSDA-ARS-ADRU, Washington State University, Pullman, Pullman, Washington, United States of America.
Daniel DesmechtPathology, Department of Morphology and Pathology, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Andrew J DavisonMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Alain VanderplasschenImmunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Funding

Medical Research Council G0801822Medical Research Council MC_UU_12014/3
6 · The paper itself

Abstract

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin.

Indexed as

AnimalsCarpsFish DiseasesHerpesviridaeHerpesviridae InfectionsHerpesvirus VaccinesLuminescent MeasurementsOpen Reading FramesRepressor ProteinsTrans-ActivatorsVaccinationVaccines, SyntheticHerpesvirus VaccinesRepressor ProteinsTrans-ActivatorsVaccines, Synthetic

Identifiers

PMID25700279
PMCPMC4336323

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.