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Volume 9
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Article

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

by
Sofie Barsøe
1,
Anna Toffan
2,
Francesco Pascoli
2,
Ansgar Stratmann
3,
Tobia Pretto
2,
Andrea Marsella
2,
Mériem Er-Rafik
4,
Niccolò Vendramin
1,
Niels J. Olesen
1,
Dagoberto Sepúlveda
1 and
Niels Lorenzen
1,*
1
National Institute of Aquatic Resources (DTU AQUA), Technical University of Denmark, 2800 Lyngby, Denmark
2
Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), 35020 Legnaro, Padua, Italy
3
W42 Biotechnology GmbH, 44227 Dortmund, Germany
4
National Center for Nano Fabrication and Characterization (DTU Nanolab), Technical University of Denmark, 2800 Lyngby, Denmark
*
Author to whom correspondence should be addressed.
Vaccines 2021, 9(5), 447; https://doi.org/10.3390/vaccines9050447
Submission received: 30 March 2021 / Revised: 22 April 2021 / Accepted: 23 April 2021 / Published: 2 May 2021
(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles)
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Abstract

Viral Nervous Necrosis (VNN) causes high mortality and reduced growth in farmed European sea bass (Dicentrarchus labrax) in the Mediterranean. In the current studies, we tested a novel Pichia-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.
Keywords: VLP vaccine; recombinant vaccine; betanodavirus; efficacy; correlate of protection VLP vaccine; recombinant vaccine; betanodavirus; efficacy; correlate of protection

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MDPI and ACS Style

Barsøe, S.; Toffan, A.; Pascoli, F.; Stratmann, A.; Pretto, T.; Marsella, A.; Er-Rafik, M.; Vendramin, N.; Olesen, N.J.; Sepúlveda, D.; et al. Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in Pichia pastoris. Vaccines 2021, 9, 447. https://doi.org/10.3390/vaccines9050447

AMA Style

Barsøe S, Toffan A, Pascoli F, Stratmann A, Pretto T, Marsella A, Er-Rafik M, Vendramin N, Olesen NJ, Sepúlveda D, et al. Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in Pichia pastoris. Vaccines. 2021; 9(5):447. https://doi.org/10.3390/vaccines9050447

Chicago/Turabian Style

Barsøe, Sofie, Anna Toffan, Francesco Pascoli, Ansgar Stratmann, Tobia Pretto, Andrea Marsella, Mériem Er-Rafik, Niccolò Vendramin, Niels J. Olesen, Dagoberto Sepúlveda, and et al. 2021. "Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in Pichia pastoris" Vaccines 9, no. 5: 447. https://doi.org/10.3390/vaccines9050447

APA Style

Barsøe, S., Toffan, A., Pascoli, F., Stratmann, A., Pretto, T., Marsella, A., Er-Rafik, M., Vendramin, N., Olesen, N. J., Sepúlveda, D., & Lorenzen, N. (2021). Long-Term Protection and Serologic Response of European Sea Bass Vaccinated with a Betanodavirus Virus-Like Particle Produced in Pichia pastoris. Vaccines, 9(5), 447. https://doi.org/10.3390/vaccines9050447

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