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

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.

Avian Bornavirus Research—A Comprehensive Review

“…In such secondary replication sites, the virus also infected various non-neuronal cell types [ 122 , 150 ]. Early shedding is also not observed after experimental PaBV-4 infection of cockatiels and African grey parrots [ 17 , 118 , 151 , 152 ]. The discrepancies between the studies of different groups are not easily explained.…”

“…While nine out of eleven experimentally infected adults showed PDD-like disease, nestlings inoculated at the age of one to six days became healthy carriers, exhibiting inflammatory lesions without clinical disease [ 124 ]. In contrast to work with BoDV-1 in mammals [ 176 ], attempts to experimentally induce or exacerbate the disease in subclinically PaBV-4-infected cockatiels by subsequent immunization with viral vector vaccines expressing PaBV-4 N and P genes failed so far [ 152 ].…”

“…To date, no vaccines for the protection against avian bornavirus infections are commercially available. Experimental studies using two different approaches have been reported, employing either recombinant bornavirus N protein [ 123 ] or viral vector vaccines expressing bornavirus N and P proteins [ 118 , 119 , 152 ].…”

“…In contrast, live viral vector vaccines expressing bornavirus antigens provided partial or complete protection against homologous and heterologous bornavirus infection of cockatiels and canaries and, consequently, also against PDD-like lesions [ 118 , 119 , 152 ]. In these studies, recombinant vectors based on Newcastle disease virus (NDV) clone 30, modified vaccinia virus Ankara (MVA) and orf virus (ORFV) were designed to carry the N and P genes of PaBV-4 or CnBV-2.…”

“…In these studies, recombinant vectors based on Newcastle disease virus (NDV) clone 30, modified vaccinia virus Ankara (MVA) and orf virus (ORFV) were designed to carry the N and P genes of PaBV-4 or CnBV-2. They were demonstrated to be safe and to induce bornavirus-specific seroconversion immunogenic in cockatiels and canaries [ 118 , 119 , 152 ]. A heterologous prime-boost vaccination regime combining the NDV and MVA vector systems delayed the course of challenge infection with high doses of PaBV-4 or CnBV-2 in cockatiels or canaries, respectively.…”