Viral vector vaccines expressing nucleoprotein and phosphoprotein genes of avian bornaviruses ameliorate homologous challenge infections in cockatiels and common canaries.

Christiane Herden,Angela Römer-Oberdörfer,Solveig Runge,Peter Staeheli,Dennis Rubbenstroth,Sara Malberg,Marita Olbert

doi:10.1038/srep36840

Christiane Herden, Angela Römer-Oberdörfer + Show 5 more

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https://doi.org/10.1038/srep36840

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Abstract

Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), an often fatal disease of parrots and related species (order Psittaciformes) which is widely distributed in captive psittacine populations and may affect endangered species. Here, we established a vaccination strategy employing two different well described viral vectors, namely recombinant Newcastle disease virus (NDV) and modified vaccinia virus Ankara (MVA) that were engineered to express the phosphoprotein and nucleoprotein genes of two avian bornaviruses, parrot bornavirus 4 (PaBV-4) and canary bornavirus 2 (CnBV-2). When combined in a heterologous prime/boost vaccination regime, NDV and MVA vaccine viruses established self-limiting infections and induced a bornavirus-specific humoral immune response in cockatiels (Nymphicus hollandicus) and common canaries (Serinus canaria forma domestica). After challenge infection with a homologous bornavirus, shedding of bornavirus RNA and viral loads in tissue samples were significantly reduced in immunized birds, indicating that vaccination markedly delayed the course of infection. However, cockatiels still developed signs of PDD if the vaccine failed to prevent viral persistence. Our work demonstrates that avian bornavirus infections can be repressed by vaccine-induced immunity. It represents a first crucial step towards a protective vaccination strategy to combat PDD in psittacine birds.

Highlights

Include apathy, lameness, ataxia, torticollis, tremor, seizures and blindness
CD4+ and CD8+ T lymphocytes were demonstrated to drive the immunopathogenesis of Borna disease (BD)[29,32,33,34,35], an immune-mediated chronic neurologic disorder occurring in a wide range of naturally and experimentally Borna disease virus 1 (BoDV-1)-infected mammals, such as horses, sheep, rats and mice
Based on the close relationship of BoDV-1 and avian bornaviruses, the similarity of microscopic lesions typical for BD and PDD in the CNS, we hypothesized that PDD is likewise an immune-mediated disease in which bornavirus-specific T lymphocytes can be decisive for both, immunopathology and protection

Summary

Introduction

Include apathy, lameness, ataxia, torticollis, tremor, seizures and blindness. Gastro-intestinal disease is caused by inflammatory lesions of the vegetative nervous system which result in reduced intestinal motility, impaired transport of the ingesta, dilated proventriculus and crop, shedding of undigested seeds with the faeces and emaciation. Viral persistence in the presence of high levels of bornavirus-specific antibodies suggests only a minor role of humoral immunity[5,15,17,21,22] This is in agreement with experimental work performed in rodents with the related mammalian Borna disease virus 1 (BoDV-1) which demonstrated CD4+ and CD8+ T lymphocytes rather than antibodies to be responsible for the protection against de novo infection[27,28,29,30,31]. Based on the close relationship of BoDV-1 and avian bornaviruses, the similarity of microscopic lesions typical for BD and PDD in the CNS, we hypothesized that PDD is likewise an immune-mediated disease in which bornavirus-specific T lymphocytes can be decisive for both, immunopathology and protection. The newly generated vaccines were used for vaccination of psittacines (cockatiels, Nymphicus hollandicus) or non-psittacine birds (common canaries, Serinus canaria forma domestica) in a heterologous prime/boost regime and safety, immunogenicity and protection against homologous bornavirus challenge were investigated in both species

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