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乙型脑炎减毒活疫苗病毒群体的异质性分析

  • 杨会强 汪伟 刘莉娜 何婷 曾献武
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  • 610023 成都生物制品研究所有限责任公司病毒疫苗研究室

网络出版日期: 2025-08-16

Heterogeneity analysis of viral population of live attenuated Japanese encephalitis vaccine (SA14-14-2 strain)

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  • Viral Vaccine Research Laboratory, Chengdu Institute of Biological Products Co., Ltd., Chengdu 610023, China

Online published: 2025-08-16

摘要

 目的  通过观察疫苗病毒群体中病毒个体的遗传和生物学特征,分析SA14-14-2株乙型脑炎减毒活疫苗病毒的均一性,为疫苗病毒的遗传稳定性提供实验证据。 方法   对3批疫苗病毒连续进行3次蚀斑纯化后,各挑选8个蚀斑纯化株,扩大培养一代。比较24个病毒纯化株的包膜(envelope,E)蛋白基因序列、单斑培养病毒滴度以及蚀斑特征。 结果   24个纯化株中共有6个病毒株(25%)的E蛋白核苷酸发生变化,其中2株(8.3%)的核苷酸变异导致其编码氨基酸发生改变,这些变异占总核苷酸变异数的28.6%。动物实验表明,这2个纯化株没有引起小鼠神经毒力变化。在所有24个纯化株中,我国2010年版药典规定的影响疫苗病毒遗传稳定性的8个E蛋白关键位点的氨基酸均未发生改变。24个纯化株病毒的蚀斑大小和形态以及单斑培养滴度均无明显差异。 结论   疫苗病毒具有典型的准种群体多样性特征,但在群体病毒中未检测到E蛋白氨基酸位点为野生型病毒位点的个体病毒,因此,疫苗病毒具有很好的减毒群体特征和遗传稳定性。

本文引用格式

杨会强 汪伟 刘莉娜 何婷 曾献武 . 乙型脑炎减毒活疫苗病毒群体的异质性分析[J]. 国际生物制品学杂志, 2015 , 38(3) : 108 -111 . DOI: 10.3760/cma.j.issn.1673-4211.2015.03.002

Abstract

 Objective   To analyze viral homogeneity of live attenuated Japanese encephalitis (JE) vaccine strain SA14-14-2 by investigating genetic and biological characteristics of individual virus in viral population of the vaccine, providing an experimental basis for the genetic stability of the vaccine virus.  Methods   Eight plaque-purified strains were selected from each of 3 lot vaccine viruses purified 3 times successively, and cultured for one passage. The gene sequences of envelope (E) protein, virus titer and plaque features were compared among the 24 strains.  Results   The nucleotide variation of E protein was found in 6 strains (25%), which resulted in corresponding amino acid changes in 2 strains (8.3%) and accounted for 28.6 % of the total nucleotide variation. The 2 strains did not enhance neurovirulence in mice. No changes were observed in 8 critical amino acid sites of E protein which influenced genetic stability as described in the current Chinese pharmacopoeia. The virus titer and plaque size and morphology were similar among the 24 strains.  Conclusions   The vaccine virus has quasispecies heterogeneity. No amino acid sites in E protein of wild strains are found in the viral population. The JE vaccine virus has good attenuated characteristics and genetic stability.
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