Buller R M, Smith G L, Cremer K, Notkins A L, Moss B
Nature. 1985;317(6040):813-5. doi: 10.1038/317813a0.
Recent advances in molecular genetics have led to the possibility of using large DNA viruses, such as vaccinia virus, as a biological delivery system for immunizing man against unrelated disease-causing agents. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg), the influenza A virus haemagglutinin, the herpes simplex virus (HSV) type 1 D glycoprotein, the rabies virus G glycoprotein and the vesicular stomatitis virus G glycoprotein were used for immunization, animals were protected upon challenge with the appropriate pathogenic agent. A major concern with using such vaccines, however, stems from the previously documented vaccinia virus-associated post-immunizing complications. We present here experimental evidence that thymidine kinase-negative (TK-) vaccinia virus recombinants, constructed by inserting a variety of DNA coding sequences into the vaccinia virus tk gene, are less pathogenic for mice than wild-type virus.
分子遗传学的最新进展使得利用大型DNA病毒（如痘苗病毒）作为生物递送系统来使人类针对无关致病因子进行免疫成为可能。当使用表达乙型肝炎病毒表面抗原（HBsAg）、甲型流感病毒血凝素、单纯疱疹病毒1型D糖蛋白、狂犬病病毒G糖蛋白和水疱性口炎病毒G糖蛋白的活痘苗病毒重组体进行免疫时，动物在受到相应病原体攻击后得到了保护。然而，使用此类疫苗的一个主要担忧源于先前记录的与痘苗病毒相关的免疫后并发症。我们在此提供实验证据，即通过将多种DNA编码序列插入痘苗病毒tk基因构建的胸苷激酶阴性（TK-）痘苗病毒重组体对小鼠的致病性低于野生型病毒。
