Retrospective genome analysis of a live vaccine strain of bovine viral diarrhea virus
Retrospective genome analysis of a live vaccine strain of bovine viral diarrhea virus
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DOI：
10.1051/vetres:2004053
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Belák, S
中科院分区：
文献类型：
--
作者：
Bálint, A;Baule, C;Belák, S
在20世纪60年代末至90年代初，中欧使用了一种活牛病毒性腹泻（BVDV）疫苗，作为俄勒冈C24V菌株的衍生物上市。由于对接种疫苗动物的粘膜疾病病例的实验室调查表明疫苗与BVDV野生型变体之间存在重组，并且重组核苷酸序列似乎与BVDV俄勒冈C24V不同，因此本回顾性研究的目的是分析预注册（此处称为BVDV- xpre）和上市（BVDV- x）批次疫苗的基因组。BVDV-Xpre全基因组分析结果证实，在疫苗生产开始时使用的原始病毒株为俄勒冈C24V。令人惊讶的是，对上市疫苗的全核苷酸序列分析显示，该菌株属于BVDV 1b亚群，与BVDV参考株Osloss同源性为93.7%。与BVDV Oregon C24V的同源性较低（77.4%），序列扫描结果表明BVDV- x的基因组并非来源于Oregon C24V。这些数据表明，很可能是在体外或体内传代疫苗开发过程中获得了与俄勒冈C24V不同的菌株。尽管发生了病毒转换，但BVDV-X疫苗一直保持着其无害性和有效性，正如定期质量检测数据所证明的那样，并且多年来一直没有注意到外来病毒的存在。这项工作的结果强调，外源性BVDV毒株污染市售活疫苗是一个真正的危险因素，需要进行明确的分析，包括分子方法，以验证其真实性。
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.