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

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.

Recombinant Modified Vaccinia Virus Ankara (MVA) Vaccines Efficiently Protect Cockatiels Against Parrot Bornavirus Infection and Proventricular Dilatation Disease

“…PaBV-4 #6758 (GenBank accession number JX065209) and PaBV-2 #17684 (JX065197) were isolated from a blue-and-gold macaw (Ara ararauna) or a cockatiel (Nymphicus hollandicus), respectively, suffering from PDD [23]. NDV and MVA vaccine constructs expressing the N or P genes of PaBV-4 #6758 (rNDV/PaBV-4/N, rNDV/PaBV-4/P, rMVA/PaBV-4/N and rMVA/PaBV-4/P) have been described in detail elsewhere [6]. The parental strains MVA-F6 [24] and recombinant NDV clone 30 [25] were kindly provided by Gerd Sutter, Munich and Angela Römer-Oberdörfer, Greifswald-Riems, respectively.…”

“…In some individuals, a PaBV infection causes proventricular dilatation disease (PDD), a peracute to chronic, often fatal disease usually associated with neurological and/or intestinal symptoms. In contrast, other persistently infected psittacines show no clinical symptoms for up to several years [5][6][7][8][9][10]. Immunopathogenesis is assumed to be required for the development of PDD, providing a possible explanation for this pattern [6].…”

“…In contrast, other persistently infected psittacines show no clinical symptoms for up to several years [5][6][7][8][9][10]. Immunopathogenesis is assumed to be required for the development of PDD, providing a possible explanation for this pattern [6]. In line with this assumption, PDD in experimentally infected cockatiels was prevented by immunosuppressive treatment with cyclosporine A (CsA) at the time of PaBV-2 inoculation [11].…”

“…At present, neither effective therapies nor immunoprophylaxis are available for avian bornavirus infection and PDD despite their considerable impact on private psittacine collections as well as on breeding projects of endangered species [16,17]. In order to protect psittacines against avian bornavirus infections, we previously generated recombinant modified vaccinia virus Ankara (MVA; family Poxviridae) and Newcastle disease virus (NDV; family Paramyxoviridae) vaccines expressing the nucleoprotein (N) and phosphoprotein (P) of PaBV-4 [6]. A combination of both vaccines protected cockatiels (Nymphicus hollandicus) against challenge infection with the closely related PaBV-2 and against PDD-associated lesions (Runge et al, 2017).…”

<b>Caracterização molecular de bornavírus, poliomavírus e circovírus em aves de cativeiro, vida livre e criação comercial</b>

“…A vacina recombinante utiliza o vacciniavírus Ankara modificado (MVA) e da doença de Newcastle (NDV) que codificam a nucleoproteína (N) e a fosforoproteína (P) de dois bornavírus aviários, o PaBv-4 (psitacídeos) e CnBV-2 (canários). Essas proteínas são amplamente expressas em células infectadas e são imunogênicos em infecções de bornavírus em mamíferos (OLBERT et al, 2016).…”