Kieny M P, Lathe R, Drillien R, Spehner D, Skory S, Schmitt D, Wiktor T, Koprowski H, Lecocq J P
Nature. 1984;312(5990):163-6. doi: 10.1038/312163a0.
Rabies is one of the oldest diseases know to man, but its successful control has remained elusive. Although effective vaccines of tissue culture origin against rabies do exist, such preparations are expensive. Live vaccinia virus (VV) recombinants expressing influenza or hepatitis B antigens have recently been used to immunize against these diseases. We have now used this approach to produce a novel rabies vaccine. We first altered the rabies glycoprotein cDNA by site-directed mutagenesis and removed the poly(dG) tail. We then aligned the modified cDNA with an early VV promoter sequence inserted within a cloned copy of the vaccinia thymidine kinase gene and transfected this plasmid into VV-infected cells. Recombination between the virus and the plasmid resulted in a recombinant virus harbouring the rabies glycoprotein cDNA. Inoculation of rabbits with the live recombinant virus induced high titres of rabies virus-neutralizing antibodies, and scarification with the recombinant VV protected mice against challenge with street rabies virus.
狂犬病是人类已知最古老的疾病之一，但其成功防控一直难以实现。尽管确实存在源自组织培养的有效的狂犬病疫苗，但此类制剂价格昂贵。表达流感或乙肝抗原的活痘苗病毒（VV）重组体最近已被用于针对这些疾病进行免疫接种。我们现在已采用这种方法来生产一种新型狂犬病疫苗。我们首先通过定点诱变改变狂犬病糖蛋白cDNA并去除聚（dG）尾。然后我们将修饰后的cDNA与插入痘苗胸苷激酶基因克隆拷贝内的早期VV启动子序列对齐，并将该质粒转染到感染VV的细胞中。病毒与质粒之间的重组产生了携带狂犬病糖蛋白cDNA的重组病毒。用这种活重组病毒接种兔子可诱导产生高滴度的狂犬病病毒中和抗体，用重组VV划痕接种可保护小鼠免受街狂犬病病毒的攻击。
