Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife

Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife
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DOI:
10.1016/j.vaccine.2008.04.007
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发表时间:
2008-06-19
期刊:
影响因子:
5.5
通讯作者:
Mueller, Thomas
Mueller, Thomas
中科院分区:
医学3区
文献类型:
--
作者:
Geue, Lutz;Schares, Susann;Mueller, Thomas

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在西欧,通过口服狂犬病疫苗(ORV),用一系列减毒狂犬病病毒株对野生动物进行狂犬病疫苗接种,已实现了从赤狐(Vulpes vulpes)中消除狂犬病。除牛痘狂犬病糖蛋白重组疫苗(VRG)外,所有菌株最初均来源于共同的祖先; Street亚拉巴马Dufferin(SAD)田间菌株。然而,在ORV存在30多年之后,仍然无法区分这些疫苗株,并且关于其减毒的遗传基础的信息很少。因此,我们对5种市售SAD疫苗病毒(SAD B19、SAD P5/88、SAG 2、SAD VA 1和SAD伯尔尼)和4种其他SAD毒株(原始SAD伯尔尼、SAD VA 1、ERA和SAD 1-3670 Wistar)的全长基因组进行了测序和比较。核苷酸测序可以明确识别每种疫苗株。系统发育分析显示,目前使用的大多数商业减毒狂犬病病毒疫苗似乎来自SAD B19,而不是SAD伯尔尼。一种市售疫苗病毒不含生产商产品信息中提及的SAD毒株。两种SAD疫苗株似乎由混合的基因组序列组成。此外,在欧洲开发的SAD衍生物中观察到靶向M和G基因3'非编码区内富含A的序列(正链)的插入缺失事件。我们的数据也支持SAD病毒欧洲分支的起源过程中可能发生重组的想法。如果得到证实,这将是RABV疫苗株中首次报道的重组事件。(C)2008爱思唯尔有限公司保留所有权利。
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. (C) 2008 Elsevier Ltd. All rights reserved.