The Plowright vaccine strain of Rinderpest virus has attenuating mutations in most genes
The Plowright vaccine strain of Rinderpest virus has attenuating mutations in most genes
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DOI：
10.1099/vir.0.80751-0
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Barrett, T
中科院分区：
文献类型：
--
作者：
Baron, MD;Banyard, AC;Barrett, T
目前使用的牛瘟病毒疫苗株是通过高毒力Kabete“O”株（KO）连续传代获得的。制备KO菌株的全长cDNA拷贝，从中拯救出致病性与野生型病毒相同的病毒。制备了一系列嵌合病毒，其中N、P、F、H或L蛋白的编码序列被来自疫苗株的相应序列替换。具有疫苗株H基因和L基因的羧基末端一半被来自疫苗株的相应序列替换的KO基病毒保留了原始KO病毒的全部或几乎全部毒力。感染含有疫苗株N、P或F基因或L基因氨基末端一半的KO病毒的动物出现高度和长期发热和白细胞减少症，但病变和其他临床体征减少或不存在;尽管部分减毒，但没有一种减毒程度接近疫苗株本身。这些数据表明，目前疫苗的高减毒和稳定性是由于许多单独突变的积累，这些突变本身都没有足够的衰弱性，以至于存在有利于回复突变体的强大选择压力。
The currently used vaccine strain of Rinderpest virus was derived by serial passage of the highly virulent Kabete 'O' strain (KO). A full-length cDNA copy of the KO strain was made from which a virus identical in pathogenicity to the wild-type virus was rescued. A series of chimeric viruses was prepared in which the coding sequences for the N, P, F, H or L proteins were replaced with the corresponding sequences from the vaccine strain. The KO-based virus with the vaccine strain H gene and that with the carboxy-terminal half of the L gene replaced with the corresponding sequence from the vaccine strain retained all or almost all of the virulence of the original KO virus. Animals infected with the KO-based virus containing the vaccine strain N, P or F gene, or the amino-terminal half of the L gene, developed high and prolonged pyrexia and leukopenia, but with reduced or absent lesions and other clinical signs; although partially attenuated, none was nearly as attenuated as the vaccine strain itself. These data indicate that the high attenuation and stability of the current vaccine are due to the accumulation of a number of separate mutations, none of which is itself so sufficiently debilitating that there is strong selective pressure in favour of the revertant.