title: Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife.
abstract: The elimination of rabies from the red fox (Vulpes vulpes) in Western Europe has been achieved by the oral rabies vaccination (ORV) of wildlife with a range of attenuated rabies virus strains. With the exception of the vaccinia rabies glycoprotein recombinant vaccine (VRG), all strains were originally derived from a common ancestor; the Street Alabama Dufferin (SAD) field strain. However, after more than 30 years of ORV it is still not possible to distinguish these vaccine strains and there is little information on the genetic basis for their attenuation. We therefore sequenced and compared the full-length genome of five commercially available SAD vaccine viruses (SAD B19, SAD P5/88, SAG2, SAD VA1 and SAD Bern) and four other SAD strains (the original SAD Bern, SAD VA1, ERA and SAD 1-3670 Wistar). Nucleotide sequencing allowed identifying each vaccine strain unambiguously. Phylogenetic analysis revealed that the majority of the currently used commercial attenuated rabies virus vaccines appear to be derived from SAD B19 rather than from SAD Bern. One commercially available vaccine virus did not contain the SAD strain mentioned in the product information of the producer. Two SAD vaccine strains appeared to consist of mixed genomic sequences. Furthermore, in-del events targeting A-rich sequences (in positive strand) within the 3' non-coding regions of M and G genes were observed in SAD-derivates developed in Europe. Our data also supports the idea of a possible recombination that had occurred during the derivation of the European branch of SAD viruses. If confirmed, this recombination event would be the first one reported among RABV vaccine strains.
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, WHO Collaborating Centre for Rabies Surveillance and Research, Wusterhausen, Germany. lutz.geue@fli.bund.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Geue
authors.forename: Susann
authors.initials: S
authors.lastname: Schares
authors.forename: Christina
authors.initials: C
authors.lastname: Schnick
authors.forename: Jeannette
authors.initials: J
authors.lastname: Kliemt
authors.forename: Aline
authors.initials: A
authors.lastname: Beckert
authors.forename: Conrad
authors.initials: C
authors.lastname: Freuling
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Conraths
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Reto
authors.initials: R
authors.lastname: Zanoni
authors.forename: Denise
authors.initials: D
authors.lastname: Marston
authors.forename: Lorraine
authors.initials: L
authors.lastname: McElhinney
authors.forename: Nicholas
authors.initials: N
authors.lastname: Johnson
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fooks
authors.forename: Noel
authors.initials: N
authors.lastname: Tordo
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
mesh_terms: D000818:Animals; D001483:Base Sequence; D005060:Europe; D005589:Foxes; D016679:Genome, Viral; D054643:INDEL Mutation; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics*; D011818:Rabies / Q000517:prevention & control / Q000662:veterinary*; D011819:Rabies Vaccines; D011820:Rabies virus / Q000235:genetics*; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014613:Vaccines, Attenuated
chemical_list: D012367:RNA, Viral; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated