Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>

Viral Nervous Necrosis (VNN) causes high mortality and reduced growth in farmed European sea bass (<i>Dicentrarchus labrax</i>) in the Mediterranean. In the current studies, we tested a novel <i>Pichia</i>-produced virus-like particle (VLP) vaccine against VNN in European sea...

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Main Authors: Sofie Barsøe, Anna Toffan, Francesco Pascoli, Ansgar Stratmann, Tobia Pretto, Andrea Marsella, Mériem Er-Rafik, Niccolò Vendramin, Niels J. Olesen, Dagoberto Sepúlveda, Niels Lorenzen
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/9/5/447
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author Sofie Barsøe
Anna Toffan
Francesco Pascoli
Ansgar Stratmann
Tobia Pretto
Andrea Marsella
Mériem Er-Rafik
Niccolò Vendramin
Niels J. Olesen
Dagoberto Sepúlveda
Niels Lorenzen
author_facet Sofie Barsøe
Anna Toffan
Francesco Pascoli
Ansgar Stratmann
Tobia Pretto
Andrea Marsella
Mériem Er-Rafik
Niccolò Vendramin
Niels J. Olesen
Dagoberto Sepúlveda
Niels Lorenzen
author_sort Sofie Barsøe
collection DOAJ
description Viral Nervous Necrosis (VNN) causes high mortality and reduced growth in farmed European sea bass (<i>Dicentrarchus labrax</i>) in the Mediterranean. In the current studies, we tested a novel <i>Pichia</i>-produced virus-like particle (VLP) vaccine against VNN in European sea bass, caused by the betanodavirus “Red-Spotted Grouper Nervous Necrosis Virus” (RGNNV). European sea bass were immunized with a VLP-based vaccine formulated with different concentrations of antigen and with or without adjuvant. Antibody response was evaluated by ELISA and serum neutralization. The efficacy of these VLP-vaccine formulations was evaluated by an intramuscular challenge with RGNNV at different time points (1, 2 and 10 months post-vaccination) and both dead and surviving fish were sampled to evaluate the level of viable virus in the brain. The VLP-based vaccines induced an effective protective immunity against experimental infection at 2 months post-vaccination, and even to some degree at 10 months post-vaccination. Furthermore, the vaccine formulations triggered a dose-dependent response in neutralizing antibodies. Serologic response and clinical efficacy, measured as relative percent survival (RPS), seem to be correlated with the administered dose, although for the individual fish, a high titer of neutralizing antibodies prior to challenge was not always enough to protect against disease. The efficacy of the VLP vaccine could not be improved by formulation with a water-in-oil (W/O) adjuvant. The developed RGNNV-VLPs show a promising effect as a vaccine candidate, even without adjuvant, to protect sea bass against disease caused by RGNNV. However, detection of virus in vaccinated survivors means that it cannot be ruled out that survivors can transmit the virus.
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spelling doaj.art-83c3fbfa181a4bfc994b68b72dfbf19a2023-11-21T18:14:00ZengMDPI AGVaccines2076-393X2021-05-019544710.3390/vaccines9050447Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>Sofie Barsøe0Anna Toffan1Francesco Pascoli2Ansgar Stratmann3Tobia Pretto4Andrea Marsella5Mériem Er-Rafik6Niccolò Vendramin7Niels J. Olesen8Dagoberto Sepúlveda9Niels Lorenzen10National Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, DenmarkIstituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Padua, ItalyIstituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Padua, ItalyW42 Biotechnology GmbH, 44227 Dortmund, GermanyIstituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Padua, ItalyIstituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Padua, ItalyNational Center for Nano Fabrication and Characterization (DTU Nanolab), Technical University of Denmark, 2800 Lyngby, DenmarkNational Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, DenmarkNational Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, DenmarkNational Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, DenmarkNational Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, DenmarkViral Nervous Necrosis (VNN) causes high mortality and reduced growth in farmed European sea bass (<i>Dicentrarchus labrax</i>) in the Mediterranean. In the current studies, we tested a novel <i>Pichia</i>-produced virus-like particle (VLP) vaccine against VNN in European sea bass, caused by the betanodavirus “Red-Spotted Grouper Nervous Necrosis Virus” (RGNNV). European sea bass were immunized with a VLP-based vaccine formulated with different concentrations of antigen and with or without adjuvant. Antibody response was evaluated by ELISA and serum neutralization. The efficacy of these VLP-vaccine formulations was evaluated by an intramuscular challenge with RGNNV at different time points (1, 2 and 10 months post-vaccination) and both dead and surviving fish were sampled to evaluate the level of viable virus in the brain. The VLP-based vaccines induced an effective protective immunity against experimental infection at 2 months post-vaccination, and even to some degree at 10 months post-vaccination. Furthermore, the vaccine formulations triggered a dose-dependent response in neutralizing antibodies. Serologic response and clinical efficacy, measured as relative percent survival (RPS), seem to be correlated with the administered dose, although for the individual fish, a high titer of neutralizing antibodies prior to challenge was not always enough to protect against disease. The efficacy of the VLP vaccine could not be improved by formulation with a water-in-oil (W/O) adjuvant. The developed RGNNV-VLPs show a promising effect as a vaccine candidate, even without adjuvant, to protect sea bass against disease caused by RGNNV. However, detection of virus in vaccinated survivors means that it cannot be ruled out that survivors can transmit the virus.https://www.mdpi.com/2076-393X/9/5/447VLP vaccinerecombinant vaccinebetanodavirusefficacycorrelate of protection
spellingShingle Sofie Barsøe
Anna Toffan
Francesco Pascoli
Ansgar Stratmann
Tobia Pretto
Andrea Marsella
Mériem Er-Rafik
Niccolò Vendramin
Niels J. Olesen
Dagoberto Sepúlveda
Niels Lorenzen
Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
Vaccines
VLP vaccine
recombinant vaccine
betanodavirus
efficacy
correlate of protection
title Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
title_full Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
title_fullStr Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
title_full_unstemmed Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
title_short Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in <i>Pichia pastoris</i>
title_sort long term protection and serologic response of european sea bass vaccinated with a betanodavirus virus like particle produced in i pichia pastoris i
topic VLP vaccine
recombinant vaccine
betanodavirus
efficacy
correlate of protection
url https://www.mdpi.com/2076-393X/9/5/447
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