DECREASED VIRULENCE OF RECOMBINANT VACCINIA VIRUS EXPRESSION VECTORS IS ASSOCIATED WITH A THYMIDINE KINASE-NEGATIVE PHENOTYPE

DECREASED VIRULENCE OF RECOMBINANT VACCINIA VIRUS EXPRESSION VECTORS IS ASSOCIATED WITH A THYMIDINE KINASE-NEGATIVE PHENOTYPE
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DOI:
10.1038/317813a0
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发表时间:
1985-01-01
期刊:
影响因子:
64.8
通讯作者:
MOSS, B
MOSS, B
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BULLER, RML;SMITH, GL;MOSS, B

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分子遗传学的最新进展使人们有可能使用大的DNA病毒,如牛痘病毒,作为一种生物传递系统,使人类免疫,对抗不相关的致病因子1 -7。当表达B肝炎病毒表面抗原(HBsAg)8、9、甲型流感病毒血凝素10、单纯疱疹病毒(HSV)1型D糖蛋白11、12、狂犬病病毒G糖蛋白13、14和水泡性口炎病毒G糖蛋白15的活牛痘病毒重组体用于免疫时,动物在用适当的病原体攻击时受到保护。然而,使用此类疫苗的一个主要问题源于先前记录的牛痘病毒相关的免疫后并发症16。我们在这里提出的实验证据表明,胸苷激酶阴性(TK-)的重组牛痘病毒,通过插入多种DNA编码序列到牛痘病毒基因,是较低的致病性比野生型病毒小鼠。
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 diseasecausing agents1–7. When live vaccinia virus recombinants expressing the hepatitis B virus surface antigen (HBsAg)8,9, the influenza A virus haemagglutinin10, the herpes simplex virus (HSV) type 1 D glycoprotein11,12, the rabies virus G glycoprotein13,14and the vesicular stomatitis virus G glycoprotein15were 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 virusassociated post-immunizing complications16. 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 virustkgene, are less pathogenic for mice than wild-type virus.