Lowe R S, Keller P M, Keech B J, Davison A J, Whang Y, Morgan A J, Kieff E, Ellis R W
Proc Natl Acad Sci U S A. 1987 Jun;84(11):3896-900. doi: 10.1073/pnas.84.11.3896.
The previous demonstration of the efficacy and tolerability of the Oka strain of varicella-zoster virus (VZV) in clinical trials involving vaccination of both normal and immunocompromised individuals has laid the foundation for its use in preventing chickenpox. In this context, VZV could be useful as a vector for vaccinating against other infectious agents as well. As an initial application, a live recombinant VZV expressing Epstein-Barr virus (EBV) membrane glycoproteins (gp350/220) was generated by inserting a gene fusion of the VZV gpI promoter and hydrophobic leader-encoding sequence with the gp350/220 coding sequence into the thymidine kinase (TK) gene of VZV (Oka). Insertion of the foreign DNA into the thymidine kinase gene was demonstrated by Southern blot analysis and the ability of the recombinant virus to replicate in the presence of bromodeoxyuridine. RNA splicing, glycosylation, and plasma membrane presentation of gp350/220 in cells infected with the recombinant virus were similar to those seen in EBV-infected cells. In addition, the expression of VZV-specific glycoproteins was unaltered by the concomitant expression of this large foreign glycoprotein. Thus, VZV can be used as a live viral vector for active immunization against EBV and other pathogens.
先前在涉及正常个体和免疫功能低下个体接种疫苗的临床试验中，水痘带状疱疹病毒（VZV）Oka株的有效性和耐受性已得到证明，这为其用于预防水痘奠定了基础。在这种情况下，VZV也可用作针对其他感染因子进行疫苗接种的载体。作为初步应用，通过将VZV gpI启动子与编码疏水前导序列的基因融合体与gp350/220编码序列插入VZV（Oka）的胸苷激酶（TK）基因中，构建了一种表达爱泼斯坦-巴尔病毒（EBV）膜糖蛋白（gp350/220）的重组活VZV。通过Southern印迹分析证实了外源DNA插入胸苷激酶基因，以及重组病毒在溴脱氧尿苷存在下的复制能力。在感染重组病毒的细胞中，gp350/220的RNA剪接、糖基化和质膜呈现与在EBV感染细胞中所见相似。此外，这种大型外源糖蛋白的共表达并未改变VZV特异性糖蛋白的表达。因此，VZV可用作针对EBV和其他病原体进行主动免疫的活病毒载体。
