Vet. Res. 36 (2005) 89-99
DOI: 10.1051/vetres:2004053

Retrospective genome analysis of a live vaccine strain of bovine viral diarrhea virus

Ádám Bálint^a, Claudia Baule^b, Vilmos Pálfi^a and Sándor Belák<sup>b

a</sup>  Department of Virology, Central Veterinary Institute, Tábornok u. 2, 1149 Budapest, Hungary
^b  Joint Research and Development Division, Departments of Virology, The National Veterinary Institute and the Swedish University of Agricultural Sciences, Ulls väg 2B, 751 89 Uppsala, Sweden

(Received 16 January 2004; accepted 5 August 2004)

Abstract - A live bovine viral diarrhea (BVDV) vaccine, marketed as a derivate of the Oregon C24V strain, was used between the end of the 1960s and the beginning of the 1990s in Central Europe. Since laboratory investigations of mucosal disease cases in vaccinated animals suggested recombinations between the vaccine and wild type variants of BVDV, and recombinational nucleotide sequences seemed distinct from BVDV Oregon C24V, the aim of the present retrospective study was to analyze the genomes of pre-registration (termed here BVDV-Xpre) and of marketed (BVDV-X) batches of the vaccine. The results of the complete genome analysis of BVDV-Xpre confirmed that the original virus strain used at the start of the vaccine production was Oregon C24V. Surprisingly, the analysis of the complete nucleotide sequence of the BVDV-X marketed vaccine revealed that this strain belongs to the BVDV 1b subgroup, with a 93.7% nucleotide sequence homology to BVDV reference strain Osloss. The homology to BVDV Oregon C24V was significantly lower (77.4%), and a thorough sequence scanning showed that the genome of BVDV-X had not derived from Oregon C24V. These data indicate the very likely scenario that a strain different to Oregon C24V was picked up during the in vitro or in vivo passages for vaccine development. Despite of the virus-switch, the BVDV-X vaccine continuously maintained its innocuity and efficacy, as proven by the regular quality testing data, and the presence of the foreign virus remained unnoticed over many years. The results of this work emphasize that the contamination of commercially available live vaccines with exogenous BVDV strains is a real risk factor, and a unequivocal analysis, including molecular methods, is needed to verify their authenticity.

Key words: bovine viral diarrhea virus / vaccine / strain switch / control

Corresponding author: Sándor Belák sandor.belak@sva.se

© INRA, EDP Sciences 2005