title: Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection.
abstract: Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. The goal of this study was to refine our avian bornavirus vaccination and infection model to better represent natural bornavirus infections in order to achieve full protection against a heterologous challenge infection. We observed that parrot bornavirus 2 (PaBV-2) readily infected cockatiels (Nymphicus hollandicus) by combined intramuscular and subcutaneous injection with as little as 102.7foci-forming units (ffu) per bird, whereas a 500-fold higher dose of the same virus administered via peroral and oculonasal route did not result in persistent infection. These results indicated that experimental bornavirus challenge infections with this virus should be performed via the parenteral route. Prime-boost vaccination of cockatiels with Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) vectors expressing the nucleoprotein and phosphoprotein genes of PaBV-4 substantially blocked bornavirus replication following parenteral challenge infection with 103.5ffu of heterologous PaBV-2. Only two out of six vaccinated birds had very low viral levels detectable in a few organs. As a consequence, only one vaccinated bird developed mild PDD-associated microscopic lesions, while mock-vaccinated controls were not protected against PaBV-2 infection and inflammation. Our results demonstrate that NDV and MVA vector vaccines can protect against invasive heterologous bornavirus challenge infections and subsequent PDD. These vector vaccines represent a promising tool to combat avian bornaviruses in psittacine populations.
authors.affiliation: Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
authors.forename: Solveig
authors.initials: S
authors.lastname: Runge
authors.affiliation: Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
authors.forename: Marita
authors.initials: M
authors.lastname: Olbert
authors.affiliation: Institute for Veterinary Pathology, University Justus Liebig Gießen, Frankfurter Str. 96, D-35392 Gießen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Herden
authors.affiliation: Institute for Veterinary Pathology, University Justus Liebig Gießen, Frankfurter Str. 96, D-35392 Gießen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Malberg
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Südufer 10, D-17493 Greifswald - Insel Riems, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Römer-Oberdörfer
authors.affiliation: Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.affiliation: Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany. Electronic address: Dennis.Rubbenstroth@uniklinik-freiburg.de.
authors.forename: Dennis
authors.initials: D
authors.lastname: Rubbenstroth
mesh_terms: D000818:Animals; D001715:Bird Diseases / Q000517:prevention & control*; D028981:Bornaviridae / Q000276:immunology*; D046410:Cockatoos; D004337:Drug Carriers; D005822:Genetic Vectors; D064789:Immunity, Heterologous; D007273:Injections, Intramuscular; D018701:Mononegavirales Infections / Q000517:prevention & control / Q000662:veterinary*; D009522:Newcastle disease virus / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D014765:Viral Vaccines
keywords: Avian bornaviruses; Modified vaccinia virus Ankara (MVA); Newcastle disease virus (NDV); Parrot bornavirus 2 (PaBV-2); Parrot bornavirus 4 (PaBV-4); Recombinant viral vector vaccines