Development Using Bioluminescence Imaging of a Recombinant Anguillid Herpesvirus 1 Vaccine Candidate Associated with Normal Replication In Vitro but Abortive Infection In Vivo
alloherpesvirus; AngHV-1; anguillid eel; Anguillid herpesvirus 1; cyprinivirus; Cyvirus; Cyvirus anguillidallo 1; European eel; in vivo bioluminescent imaging; recombinant vaccine; Immunology; Pharmacology; Drug Discovery; Infectious Diseases; Pharmacology (medical)
Abstract :
[en] Background/Objectives: Anguillid herpesvirus 1 (AngHV-1) (recently renamed Cyvirus anguillidallo 1) is the etiologic agent of a lethal disease that affects several eel species. It is thought to be one of the main infectious agents causing a population decline in wild eels and economic loss within the eel aquaculture sector. To date, no vaccines are available against AngHV-1. Recently, we developed a safe and efficacious live attenuated recombinant vaccine against Cyprinid herpesvirus 3 (CyHV-3). This CyHV-3 recombinant vaccine encodes a deletion of ORF57. Orthologues of CyHV-3 ORF57 exist in Cyprinid herpesvirus 2 (CyHV-2, ORF57) and AngHV-1 (ORF35). Methods: In the present study, using recombinant strains and bioluminescent in vivo imaging, we investigated the effect of AngHV-1 ORF35 deletion on virus replication in vitro, virulence in vivo, and the potential of an AngHV-1 ORF35-deleted recombinant as a vaccine candidate for the mass vaccination of eels by immersion. With this goal in mind, we produced ORF35-deleted recombinants using two parental strains: a UK strain and a recombinant derived from the former strain by insertion of a Luciferase–GFP reporter cassette into a non-coding intergenic region. Results: Analyses of ORF35-deleted recombinants led to the following observations: (i) AngHV-1 ORF35 is not essential for viral growth in cell culture, and its deletion does not affect the production of extracellular virions despite reducing the size of viral plaque. (ii) In contrast to what has been observed for CyHV-3 ORF57 and CyHV-2 ORF57, in vivo bioluminescent analyses revealed that AngHV-1 ORF35 is an essential virulence factor and that its deletion led to abortive infection in vivo. (iii) Inoculation of the AngHV-1 ORF35-deleted recombinant by immersion induced a protective immune response against a wild-type challenge. This protection was shown to be dose-dependent and to rely on the infectivity of AngHV-1 ORF35-deleted virions. Conclusions: This study suggests that the AngHV-1 ORF35 protein has singular properties compared to its orthologues encoded by CyHV-2 and CyHV-3. It also supports the potential of AngHV-1 ORF35-deleted recombinants for the mass vaccination of eels by immersion.
Zhang, Haiyan ✱; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Sridhar, Arun ✱; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Delrez, Natacha ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
He, Bo ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Immunologie vétérinaire
Fourny, Sophie ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Gao, Yuan; Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
Donohoe, Owen ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire ; Bioscience Research Institute, Technological University of the Shannon, Athlone, Ireland
Vanderplasschen, Alain ✱; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Immunologie vétérinaire ; WEL Research Institute, Wavre, Belgium
✱ These authors have contributed equally to this work.
Language :
English
Title :
Development Using Bioluminescence Imaging of a Recombinant Anguillid Herpesvirus 1 Vaccine Candidate Associated with Normal Replication In Vitro but Abortive Infection In Vivo
Publication date :
December 2024
Journal title :
Vaccines
ISSN :
2076-393X
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI)
EMFF - European Maritime and Fisheries Fund ULiège - University of Liège F.R.S.-FNRS - Fonds de la Recherche Scientifique Walloon Region
Funding text :
A.S. is a post-doctoral research fellow of the Wel Research Institute (Welbio). N.D. is a research fellow of the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS). H.Z. and B.H. are research fellows of the Chinese Scholarship Council. This work was supported by the Wel Research Institute (WELBIO-CR-2022 A-14 12), the European Maritime and Fisheries Fund (Eel4ever project), the University of Li\u00E8ge (ARC23/27-15), the Fonds National Belge de la Recherche Scientifique (FNRS) (CDR J.0094.15 and PDR T.0241.19), and the Walloon Region (ERANets NucNanoFish 2010052).
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