Adams Mathew M, van Leeuwen Barbara H, McFadden Grant, Kerr Peter J
School of Biochemistry and Molecular Biology, College of Science, The Australian National University, Canberra, ACT 0200, Australia.
Vet Res. 2008 Nov-Dec;39(6):60. doi: 10.1051/vetres:2008037. Epub 2008 Sep 9.
Deletion of the M063 gene from myxoma virus produces a virus that is unable to replicate in rabbit cells in vitro or in live rabbits but can be propagated in non-rabbit cell lines. A targeted M063 deletion mutant was constructed in the attenuated Uriarra strain of myxoma virus and the ability of this virus to act as a safe, non-transmissible vaccine against myxomatosis was tested in outbred laboratory rabbits. Immunization with the M063 deletion vaccine provided good short-term protection against lethal challenge with virulent myxoma virus. Long-term protection was similar to reported results with heterologous live virus, with some rabbits protected but others succumbing to challenge. Replication-deficient poxvirus vaccines, like the Modified Vaccinia Virus Ankara (MVA) in man and the myxoma virus vaccine described here in rabbits, are very attractive from a safety perspective. Seasonal boosting would be predicted to provide long-term protection. Targeted host-range gene deletions could have potential for rapid development of poxvirus vaccines in general.
从黏液瘤病毒中删除M063基因可产生一种病毒，该病毒无法在体外兔细胞或活兔体内复制，但可在非兔细胞系中繁殖。在黏液瘤病毒的减毒Uriarra株中构建了靶向M063缺失突变体，并在远交系实验兔中测试了这种病毒作为一种安全、不可传播的抗黏液瘤病疫苗的能力。用M063缺失疫苗免疫可提供良好的短期保护，抵抗强毒黏液瘤病毒的致死性攻击。长期保护与用异源活病毒报道的结果相似，一些兔子受到保护，但其他兔子则死于攻击。从安全性角度来看，复制缺陷型痘病毒疫苗，如人类使用的改良痘苗病毒安卡拉（MVA）和本文所述的兔黏液瘤病毒疫苗，非常具有吸引力。预计季节性加强免疫将提供长期保护。一般而言，靶向宿主范围基因缺失可能有助于痘病毒疫苗的快速开发。
