Reference : Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Usin...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
http://hdl.handle.net/2268/179932
Rational Development of an Attenuated Recombinant Cyprinid Herpesvirus 3 Vaccine Using Prokaryotic Mutagenesis and In Vivo Bioluminescent Imaging
English
Boutier, Maxime mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Ronsmans, Maygane mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Ouyang, Ping mailto [Sichuan Agricultural University > College of Veterinary Medicine > Key Laboratory of Animal Disease > >]
Fournier, Guillaume mailto []
Reschner, Anca mailto []
Rakus, Krzysztof mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Wilkie, Gavin S mailto []
Farnir, Frédéric mailto [Université de Liège - ULiège > Département de productions animales > Biostatistiques et bioinformatique appliquées aux sc. vétér. >]
Bayrou, Calixte mailto [Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies >]
Lieffrig, François mailto []
Li, Hong mailto []
Desmecht, Daniel mailto [Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies >]
Davison, Andrew J mailto []
Vanderplasschen, Alain mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
20-Feb-2015
PLoS Pathogens
Public Library of Science
11
2
e1004690
Yes (verified by ORBi)
International
1553-7366
1553-7374
San Francisco
CA
[en] Cyprinid herpesvirus 3 ; Koi herpesvirus ; CyHV-3 ; KHV ; attenuated vaccine ; fish ; carp ; in vivo imaging ; cyprinus carpio ; mutagenesis ; modified-live vaccine ; aquaculture
[en] 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.
Fundamental and Applied Research for Animals & Health
F.R.S.-FNRS - Fonds de la Recherche Scientifique ; BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique ; MSD Animal Health grant ; UK Medical Research Council grant
Researchers ; Professionals
http://hdl.handle.net/2268/179932
10.1371/journal.ppat.1004690
http://www.ncbi.nlm.nih.gov/pubmed/25700279
https://www.researchgate.net/publication/272520843_Rational_Development_of_an_Attenuated_Recombinant_Cyprinid_Herpesvirus_3_Vaccine_Using_Prokaryotic_Mutagenesis_and_In_Vivo_Bioluminescent_Imaging

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