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

Dennis Rubbenstroth,Christiane Herden,Sara Malberg,Ralf Amann,Isabell Rall

doi:10.3390/v11121130

Abstract

Parrot bornaviruses (PaBVs) are the causative agents of proventricular dilatation disease (PDD), a chronic and often fatal neurologic disorder in Psittaciformes. The disease is widely distributed in private parrot collections and threatens breeding populations of endangered species. Thus, immunoprophylaxis strategies are urgently needed. In previous studies we demonstrated a prime-boost vaccination regime using modified vaccinia virus Ankara (MVA) and Newcastle disease virus (NDV) constructs expressing the nucleoprotein and phosphoprotein of PaBV-4 (MVA/PaBV-4 and NDV/PaBV-4, respectively) to protect cockatiels (Nymphicus hollandicus) against experimental challenge infection. Here we investigated the protective effect provided by repeated immunization with either MVA/PaBV-4, NDV/PaBV-4 or Orf virus constructs (ORFV/PaBV-4) individually. While MVA/PaBV-4-vaccinated cockatiels were completely protected against subsequent PaBV-2 challenge infection and PDD-associated lesions, the course of the challenge infection in NDV/PaBV-4- or ORFV/PaBV-4-vaccinated birds did not differ from the unvaccinated control group. We further investigated the effect of vaccination on persistently PaBV-4-infected cockatiels. Remarkably, subsequent immunization with MVA/PaBV-4 and NDV/PaBV-4 neither induced obvious immunopathogenesis exacerbating the disease nor reduced viral loads in the infected birds. In summary, we demonstrated that vaccination with MVA/PaBV-4 alone is sufficient to efficiently prevent PaBV-2 challenge infection in cockatiels, providing a suitable vaccine candidate against avian bornavirus infection and bornavirus-induced PDD.

Highlights

Avian bornaviruses belong to the family Bornaviridae and are widely distributed in captive populations of parrots and related species (Psittaciformes) [1,2]
To evaluate the protective effect provided by recombinant Newcastle disease virus (NDV), modified vaccinia virus Ankara (MVA) and Orf virus (ORFV) vaccines expressing Parrot bornaviruses (PaBVs)-4 antigens, three groups of four cockatiels were intramuscularly vaccinated three times in 2-week intervals with either NDV, MVA or ORFV constructs encoding PaBV-4 N and P
Studies on Borna disease virus 1 (BoDV-1) infection in rodents suggest that immunization in the presence of an established bornavirus infection induces immunopathology and exacerbates disease [12,31]

Summary

Introduction

Avian bornaviruses belong to the family Bornaviridae and are widely distributed in captive populations of parrots and related species (Psittaciformes) [1,2]. 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]. This is in congruence with the closely related mammalian Borna disease virus 1 (BoDV-1; species Mammalian 1 orthobornavirus), which causes T cell-mediated immunopathogenesis in various mammalian hosts [12,13,14,15]

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Results

Conclusion