Adams Mathew M, van Leeuwen Barbara H, Kerr Peter J
School of Biochemistry and Molecular Biology, College of Science, The Australian National University, Canberra, ACT 0200, Australia.
Vaccine. 2008 Oct 29;26(46):5843-54. doi: 10.1016/j.vaccine.2008.08.036. Epub 2008 Sep 25.
Three deletion mutant viruses were constructed as potential vaccines against myxomatosis using the naturally attenuated Uriarra strain of myxoma virus. The viruses had the M007 (encodes a secreted gamma-interferon receptor homologue), M010 (encodes an epidermal growth factor homologue) and M011 (encodes an inhibitor of apoptosis in T lymphocytes) genes insertionally inactivated as either DeltaM007, DeltaM010/M011 or DeltaM007/M010/M011. All three viruses induced high serum antibody titres. Rabbits immunized with these deletion mutants were protected from lethal challenge. However, immunization of adult rabbits with DeltaM007 or DeltaM010/M011 was associated with mild clinical signs that would make these viruses unacceptable as vaccines. The triple gene knock-out virus (DeltaM007/M010/M011) termed Ur-TKO was very well tolerated by adult and juvenile rabbits. The low pathogenicity of Ur-TKO was confirmed by pathogenesis studies in domestic and wild rabbits.
利用天然减毒的黏液瘤病毒乌里阿拉毒株构建了三种缺失突变病毒，作为抗黏液瘤病的潜在疫苗。这些病毒的M007（编码一种分泌型γ干扰素受体同源物）、M010（编码一种表皮生长因子同源物）和M011（编码T淋巴细胞凋亡抑制剂）基因分别被插入失活，形成ΔM007、ΔM010/M011或ΔM007/M010/M011。这三种病毒均诱导产生了高血清抗体滴度。用这些缺失突变体免疫的兔子对致死性攻击具有抵抗力。然而，用ΔM007或ΔM010/M011免疫成年兔子会出现轻微的临床症状，这使得这些病毒不能作为疫苗使用。三重基因敲除病毒（ΔM007/M010/M011），即Ur-TKO，成年和幼年兔子对其耐受性都很好。在家兔和野兔中进行的发病机制研究证实了Ur-TKO的低致病性。
