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中国脊髓灰质炎(脊灰)病毒疫苗株普遍存在基因变异的现象,如重组、点突变等〔1〕。我们选出10株有代表性的变异株,在具有人脊灰病毒受体基因的转基因小鼠PVR-Tg21〔2〕中做毒力分析,发现Sabin1基因型(VP1)与野毒基因型(3D)的重组株显示很强的神经毒力,其PD50inTCID50(简称PD50)值为4.5,而Sabin1标准株的PD50值大于8.0。另外两株Ⅰ型疫苗株只在关键性核苷酸位点发生突变,只在位点525-U发生突变的一株,其PD50值为5.0,另一株在位点480-G及2795-A突变,其PD50值为5.8,均显示较强的神经毒力。一株Sabin2基因型(VP1)与Sabin3基因型(3D)的重组株,其神经毒力(PD50≥5.9)亦明显高于Sabin2标准株(PD50>7.5);而1株Sabin2基因型(VP1)与(Sabin1+Sabin2)基因型(3D)重组株的神经毒力(PD50=7.50)无明显提高。对Ⅲ型疫苗株的神经毒力分析发现,1株Sabin3基因型(VP1)与Non-Sabin基因型(3D)重组株的神经毒力,高于仅在核苷酸位点472-U突变的一株疫苗株。值得提出的是,另一株Ⅲ型疫苗?
China polio (polio) virus vaccine strains widespread phenomenon of gene mutation, such as recombination, point mutations [1]. We selected 10 representative mutants and did virulence analysis in PVR-Tg21 (2) transgenic mice harboring human poliovirus receptor gene. It was found that Sabin1 genotype (VP1) and wild type genotype ) Showed highly potent neurotoxicity with a PD50inTCID50 (referred to as PD50) value of 4.5 and a Sabin1 standard strain with a PD50 value of greater than 8.0. In addition, the two strains of type I vaccine only mutated at the key nucleotide sites. Only one locus 525-U mutation had a PD50 value of 5.0 and the other was at site 480-G and 2795-A mutation, the PD50 value of 5.8, all showed strong neurotoxicity. A recombinant strain of Sabin2 genotype (VP1) and Sabin3 genotype (3D) also showed significantly higher neurotoxicity (PD50≥5.9) than Sabin2 standard (PD50> 7.5). One Sabin2 gene (VP1) and (Sabin1 + Sabin2) genotype (3D) recombinant strains of neurotoxicity (PD50 = 7.50) no significant increase. The neurovirulence analysis of the type III vaccine strain revealed that the virulence of one Sabin3 genotype (VP1) and the Non-Sabin genotype (3D) recombinant strain was higher than that of the 472-U mutant only at the nucleotide position A vaccine strain. It is worth mentioning that another type III vaccine?